ADHD and autism (ASD) pathways (WP5420)

Homo sapiens

Pathways associated with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Neurodivergent conditions linked in studies to these pathways include ADHD, autism, dyspraxia, dyslexia, dyscalculia, bipolar disorder, obsessive-compulsive disorder, sensory processing disorders, and Tourette syndrome. This aims to be a highly detailed, comprehensive map of the metabolic pathways associated with these disorders, from indicated input vitamins through synthesis to signaling across the synaptic gap, re-uptake, and catabolism receptors. This pathway is constructed with computational analysis and machine learning in mind. In cases where there is a trade-off between readability and parametric accuracy, parametric accuracy is prioritized. This pathway is inspired by Kimberly Kitzerow and her meta-analysis research on the biomechanisms and pathways behind invisible illnesses. https://kimberly102347.com/the-chart/ Pathways included in this map: One-Carbon (1C), Metabolism Folate Cycle, Methionine Cycle, Tetrahydrobiopterin (BH4) Pathway, Neurotransmitter Synthesis, Reuptake, and Breakdown, Kynurenine Pathway (KP), Endocannabinoid System (ECS), Neuroreceptor Dynamics in the Synaptic Cleft, ROS Reactive Oxygen Stress.

Authors

Alexmadsen1 , Egon Willighagen , Kristina Hanspers , Lars Willighagen , Eric Weitz , and Denise Slenter

Activity

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

attention deficit hyperactivity disorder autism spectrum disorder generalized anxiety disorder anxiety disorder

Pathway Ontology

endocannabinoid metabolic pathway kynurenine metabolic pathway folate metabolic pathway epinephrine signaling pathway neurotransmitter metabolic pathway endocannabinoid signaling pathway methionine cycle/metabolic pathway folate mediated one-carbon metabolic pathway tetrahydrobiopterin metabolic pathway

Participants

Label Type Compact URI Comment
L-ornithine Metabolite chebi:46911
sarcosine Metabolite chebi:57433
vitamin B6 Metabolite chebi:27306
fumarate Metabolite chebi:29806
guanidinoacetate Metabolite chebi:57742
Mo-MPT Metabolite chebi:71302 Mo-molybdopterin
hydroxocobalamin Metabolite chebi:27786
NMPEA Metabolite chembl.compound:CHEMBL45763
2-phenylacetaldehyde Metabolite chebi:16424
Zn2+ Metabolite chebi:29105
phenylethylamine2-phenylethylaminePEA Metabolite chebi:225237
CARI Metabolite chebi:77657
PA Metabolite chebi:17405 4-pyridoxic acid
DAG Metabolite kegg.drug:C00165
glycine Metabolite chebi:57305
creatine Metabolite chebi:57947
MN2+ Metabolite chebi:29035
THF-polyglutamate Metabolite chebi:28624
3-MT SO Metabolite chebi:133708
Imidazole-4-acetate Metabolite chebi:16974
a 1-(1-hydroxyalkyl)-sn-glycerol Metabolite chebi:73418
FMN Metabolite chebi:cHEBI:58210
H2O2 Metabolite chebi:16240
DHMA Metabolite chebi:27637
1-O-(1,2-saturated-alkyl)-sn-glycerol Metabolite chebi:83957
q-BH2 Metabolite chebi:43029
angiotensin I Metabolite chebi:147350
SAMe Metabolite chebi:59789
L-tryptophan Metabolite chebi:57912
serine Metabolite wikidata:Q82980657
NMN-SO Metabolite hmdb:HMDB0240719
PPH4 Metabolite chebi:17804
serotonin Metabolite chebi:350546
sepiapterin Metabolite chebi:16095
MG2+ Metabolite chebi:18420
NormetanephrineNM Metabolite chebi:89951
THF Metabolite chebi:26907
NO Metabolite chebi:16480
formate Metabolite chebi:15740
L-citrulline Metabolite chebi:57743
FAD Metabolite chebi:57692
Metanephrine Metabolite chebi:89633
tyramine Metabolite chebi:327995
glycine betaine Metabolite chebi:17750
taurine Metabolite chebi:507393
5-MTHF Metabolite chebi:15641
MOPGAL Metabolite chebi:27932
AdoCbl Metabolite chebi:18408
MeCbl(III)alamin Metabolite chebi:28115
deamido-NAD+ Metabolite chebi:58437
L-histidinol Metabolite chebi:57699
DHNTP Metabolite chebi:18372
L-cysteate Metabolite chebi:58090
melatonin Metabolite chebi:16796
3-MT Metabolite chebi:1582
5-10MeTHF Metabolite chebi:20502
10-formyl-THF Metabolite chebi:15637
O2− Metabolite chebi:18421
DOPL Metabolite chebi:27978
5, 10-MTHFPG Metabolite chebi:60976
4-aminobutanoate Metabolite chebi:30566
L-tyrosine Metabolite chebi:58315
MN-SO4 Metabolite hmdb:HMDB0240719
nicotinate D-ribonucleotide(2−) Metabolite chebi:57502
N-METHYL-HISTAMINE Metabolite chebi:58600
B9 Metabolite chebi:27470
dopamine Metabolite chebi:59905
cysteine sulfinate Metabolite chebi:61085
SAH Metabolite chebi:16680
L-dopa Metabolite chebi:57504
MHPGMOPEG Metabolite chebi:1576
DOPET Metabolite chebi:68889
FLAD1 Metabolite chebi:Q8NFF5
Biopterin Metabolite chebi:15373
histamine Metabolite chebi:58432
1′-OXPH4 Metabolite hmdb:HMDB0013642 1'-oxo-2'-hydroxypropyl-tetrahydropterin
H4gtpGPT Metabolite chebi:
N-Methylhistamine Metabolite chebi:29009
imidazole-4-acetaldehyde Metabolite chebi:27398
q-H2BPT Metabolite chebi:43120
NAS Metabolite chebi:17697
L-alanine Metabolite chebi:57972
5-MT Metabolite chebi:2089
Fe2+ Metabolite chebi:29033
glycerol Metabolite chebi:17754
O2 Metabolite chebi:5379
L-histidine Metabolite chebi:57595
DOPAC Metabolite chebi:41941
fatty aldehydes Metabolite chebi:35746
DHPG Metabolite chebi:1387
hemiacetals Metabolite chebi:5653
alkylglycerols Metabolite chebi:52575
Xanthurenic acid Metabolite chebi:10072
2-oxoglutarate Metabolite chebi:16810
Met Metabolite chebi:64558
noladin ether Metabolite chebi:75913
acetate Metabolite chebi:58251
DHF Metabolite chebi:23743
MoCo Metabolite chebi:71302
L-glutamine Metabolite chebi:58359
(4aS,6R)-4a-hydroxy - BH4 Metabolite chebi:15642
5-Hial Metabolite chebi:50157
moco sulfide Metabolite chebi:82685
HVAL Metabolite chebi:173769 HVAL = Homovanillyl = alcohol(4-Hydroxy-3-methoxyphenyl)ethanol
glycerol 3-phosphate Metabolite chebi:57597
Angiotensinogen Metabolite chebi:2720
hypotaurine Metabolite chebi:57853
DOPGAL Metabolite chebi:180943
B2 Metabolite chebi:17015
OH- Metabolite chebi:16234
6R-BH4 Metabolite chebi:59560
adrenaline Metabolite chebi:28918
arachidonic acid Metabolite chebi:15843
cystathionine Metabolite chebi:58161
DOPEG Metabolite chebi:1387
5-hydroxy-L-tryptophan Metabolite chebi:58266
L-arginine Metabolite chebi:32682
L-cysteine Metabolite chebi:35235
L-phenylalanine Metabolite chebi:58095
2′-OXPH4 Metabolite chebi:17248 1'-hydroxy-2'-oxopropyl-tetrahydropterin (2'-OXPH4)
homocysteine Metabolite chebi:58199
BH4 Metabolite chebi:15372
BH27,8-dihydrofolate Metabolite chebi:64240
NADP Metabolite chebi:58349
NADPH Metabolite chebi:57783
ONOO- Metabolite chebi:25941
norepinephrine Metabolite chebi:72587
VMA Metabolite chebi:27622
HVA Metabolite chebi:545959 AKA HVA
5-HIAA Metabolite chebi:27823 AKA 5-HIAA
Clonidine Metabolite chebi:46631
Guanfacine Metabolite hmdb:HMDB15153
Prazosin Metabolite hmdb:HMDB14600
L-glutamate Metabolite chebi:29985
L-Asp Metabolite chebi:29991
Ca2+ Metabolite chebi:29108
oxytocin Metabolite chebi:7872
angiotensin II Metabolite chebi:58506
3-Hydroxykynurenine Metabolite chebi:1547
Kynurenic Acid Metabolite chebi:58454
Picolinic Acid Metabolite chebi:28747
3-Hydroxyanthranilic Acid Metabolite chebi:15793
Quinolinic AcidQUIN Metabolite chebi:16675
Anthranilic Acid Metabolite chebi:16567
Kynurenine Metabolite chebi:57959
NAD+ Metabolite chebi:13389
QUIN Metabolite chebi:16675
NorepinephrineNA Metabolite chebi:72587
gamma-hydroxybutyrate Metabolite wikidata:Q207920
GABA Metabolite chebi:59888
succinate Metabolite wikidata:Q213050
succinic semialdehyde Metabolite chebi:57706
2A-3OBU Metabolite chebi:78948
L-threonine Metabolite chebi:57926
PLP Metabolite chebi:597326
Succinyl-CoA Metabolite chebi:15380
R-cob(III)alamin Metabolite chebi:140785
cob(I)alamin Metabolite chebi:15982
Methylmalonyl-CoA Metabolite chebi:16625
FMN Metabolite chebi:cHEBI:58210 cofactor
11-OH-THC Metabolite hmdb:HMDB0060906
Phosphatidylethanolamine Metabolite hmdb:HMDB0060501
cAMP Metabolite chebi:58165
NAPE Metabolite chebi:61232
Arachidonic acid Metabolite hmdb:HMDB0001043
THC Metabolite hmdb:HMDB0041865 Tetrahydrocannabinol (THC) is the primary psychoactive compound found in cannabis plants. Its effects on cannabinoid receptors CNR1 (CB1) and CNR2 (CB2) are well-documented: CB1 Receptor Interaction: THC is a partial agonist at the CB1 receptor. When it binds to the CB1 receptor, it activates the receptor to a degree, eliciting a psychoactive response which is often associated with the 'high' experienced from cannabis consumption. CB2 Receptor Interaction: THC is also a partial agonist at the CB2 receptor, although its affinity for the CB2 receptor is less compared to the CB1 receptor. The activation of CB2 receptors by THC is associated with some of the medicinal properties of cannabis, such as its anti-inflammatory effects. In summary, THC acts as a partial agonist at both CB1 and CB2 receptors, stimulating these receptors to produce a variety of effects in the body, including psychoactive and potential therapeutic effects. Unlike CBD, THC does not act as an antagonist or inhibitor at these receptors, and its binding and activation of CB1 and CB2 receptors are central to its effects.
1''-hydroxycannabidiol Metabolite chebi:133056
2-AG Metabolite chebi:52392 2-arachidonoylglycerol
ATP Metabolite hmdb:HMDB0000538
AEA Metabolite chebi:2700 anandamide
COOH-THC Metabolite chebi:77273
CBD Metabolite chebi:69478 Per GPT: Cannabidiol (CBD) has a complex interaction with cannabinoid receptors CNR1 (CB1) and CNR2 (CB2). It doesn't bind to these receptors with high affinity in the same way that other cannabinoids like THC do. Here's a breakdown of CBD's interaction with CB1 and CB2 receptors: CB1 Receptor Interaction: CBD is often described as an antagonist or inverse agonist at the CB1 receptor, meaning it can block or inhibit the effects of CB1 agonists like THC. By doing so, it can counteract some of the psychoactive effects of THC. CB2 Receptor Interaction: At the CB2 receptor, CBD acts as an inverse agonist, similar to its action at the CB1 receptor. The CB2 receptor is mainly found in the immune system, and its activation is associated with anti-inflammatory effects. Allosteric Modulation: Besides acting as an antagonist or inverse agonist, CBD is also known as an allosteric modulator. As an allosteric modulator, CBD can change the shape of the CB1 receptor in a way that inhibits other compounds' ability to bind to the receptor or changes the effect if binding occurs. This is not the same as directly binding to the receptor and activating it (as an agonist would) or blocking its activation (as an antagonist would). Indirect Effects: CBD has several indirect effects on the endocannabinoid system, such as increasing anandamide levels by inhibiting its uptake and degradation. Anandamide is an endogenous cannabinoid that acts as an agonist at both CB1 and CB2 receptors. Non-Cannabinoid Receptor Interactions: CBD also interacts with several other non-cannabinoid receptors and channels which contribute to its wide range of effects.
2''-hydroxycannabidiol Metabolite chebi:133058
3''-hydroxycannabidiol Metabolite chebi:133059
4''-hydroxycannabidiol Metabolite chebi:133055
5''-hydroxycannabidiol Metabolite chebi:133062
6a-hydroxycannabidiol Metabolite chebi:133049
6b-hydroxycannabidiol Metabolite chebi:133052
7-hydroxycannabidiol Metabolite chebi:133053
CBD Metabolite chebi:69478
KUVAN(BH4 Supplement) Metabolite chebi:15372
Amphetamine Metabolite drugbank:DB00182
Viloxazine(Qelbree) Metabolite chebi:94405
Ketamine Metabolite chebi:6121
Methylphenidate(Ritalin) Metabolite hmdb:HMDB14566
NDRIBupropion (Wellbutrin) Metabolite drugbank:DB01156
Risperidone Metabolite drugbank:DB00734
PIP2 Metabolite wikidata:Q413692
PIP3 Metabolite chebi:16618
cob(II)alamin Metabolite chebi:16304 Should be cob(II)alamin according to literature
FAD Metabolite chebi:57692 cofactor
PtdIns3P Metabolite chebi:26034
acetyl-CoA Metabolite chebi:57288
malonyl-CoA Metabolite chebi:57384
Cbl Metabolite chebi:23334
cobalamins Metabolite chebi:23334
PLP Metabolite chebi:597326 pyridoxal 5'-phosphate
PMP Metabolite chebi:18335 pyridoxamine 5'-phosphate
PNP Metabolite chebi:28803 pyridoxine 5′-phosphate
PNG Metabolite chebi:17382 pyridoxine-5′-β-D-glucoside
PL Metabolite chebi:17310 pyridoxal
PM Metabolite chebi:57761 pyridoxamine
PN Metabolite chebi:28803 pyridoxine, vitamin B6
Mg2+ Metabolite chebi:18420
ATP Metabolite chebi:30616
XMP Metabolite chebi:57464
SAICARP Metabolite chebi:58443
AICA-riboside Metabolite chebi:28498
AMP Metabolite chebi:456215
Xanthosine Metabolite chebi:18107
2'-Deoxyadenosine Metabolite chebi:17256
Inosine Metabolite chebi:17596
GDP Metabolite chebi:58189
SAICA-riboside Metabolite chebi:18319
dGDP Metabolite chebi:58595
Succinyladenosine Metabolite chebi:71169
dATP Metabolite chebi:61404
AICARP Metabolite chebi:58475
2,8-Dihydroxyadenine Metabolite wikidata:Q4596812
dADP Metabolite chebi:57667
Adenosine Metabolite chebi:16335
dAMP Metabolite chebi:58245
ITP Metabolite chebi:61402 is a nucleoside triphosphate(4−)
Hypoxanthine Metabolite chebi:17368
Guanosine Metabolite chebi:16750
S-AMP Metabolite chebi:57567 succinyladenosine monophosphate
Xanthine Metabolite chebi:17712
ADP Metabolite chebi:456216
GTP Metabolite chebi:37565
dGTP Metabolite chebi:16497
Urate Metabolite chebi:17775
Adenine Metabolite chebi:16708
Guanine Metabolite chebi:16235
dGMP Metabolite chebi:57673
FAICARP Metabolite chebi:58467
2-Deoxyguanosine Metabolite chebi:17172
GMP Metabolite chebi:58115
2'-deoxyinosine Metabolite chebi:28997
IMP Metabolite chebi:58053
Propranolol Metabolite drugbank:DB00571
Nadolol Metabolite drugbank:DB01203
Dextroamphetamine Metabolite drugbank:DB01576
PRKAA1 GeneProduct uniprot:Q13131
GATM GeneProduct uniprot:P50440
CALM3 GeneProduct uniprot:P0DP23
PLCG1 GeneProduct uniprot:P19174
SESN1 GeneProduct uniprot:Q9Y6P5
CNTN6 GeneProduct uniprot:Q12860
rs237897 GeneProduct dbsnp:rs237897
HNMT GeneProduct uniprot:P50135
ACE GeneProduct uniprot:P12821
HCFC1 (cblX) GeneProduct uniprot:P51610
CNTN1 GeneProduct uniprot:Q9UQ52
FOLH1 GeneProduct uniprot:Q04609
CNTNAP4 GeneProduct uniprot:Q9C0A0
SLC17A6 GeneProduct uniprot:Q9P2U8
DAG1 GeneProduct uniprot:Q14118
GCAT GeneProduct uniprot:O75600
rs35062132 GeneProduct dbsnp:rs35062132
rs237889 GeneProduct dbsnp:rs237889
SLC17A8 GeneProduct uniprot:Q9P2U8
AOC1 GeneProduct uniprot:P19801
SIRT3 GeneProduct uniprot:Q9NTG7
ALDH9A1 GeneProduct uniprot:P49189
HDC GeneProduct uniprot:P19113
FAAH2 GeneProduct uniprot:Q6GMR7
CNTNAP2 GeneProduct uniprot:Q9UHC6
rs2268491 GeneProduct dbsnp:rs2268491
rs7632287 GeneProduct dbsnp:rs7632287
CNTN2 GeneProduct uniprot:O94779
CNTNAP1 GeneProduct uniprot:P78357
SLC52A2 GeneProduct uniprot:Q9HAB3
CNTN5 GeneProduct uniprot:Q02246
rs53576 GeneProduct dbsnp:rs53576
SLC52A1 GeneProduct uniprot:Q9NWF4
rs151257822 GeneProduct dbsnp:rs151257822
rs237902 GeneProduct dbsnp:rs237902
SLC52A3 GeneProduct uniprot:Q9NQ40
CNTN4 GeneProduct uniprot:Q9P232
rs237887 GeneProduct dbsnp:rs237887
CDO1 GeneProduct uniprot:Q16878
FMO1 GeneProduct uniprot:Q01740
CNTN3 GeneProduct uniprot:Q8IWV2
CNTNAP3 GeneProduct uniprot:Q9BZ76
GLUL GeneProduct uniprot:P15104
rs2254298 GeneProduct dbsnp:rs2254298
DRD3 GeneProduct ncbigene:282554
DRD4 GeneProduct uniprot:P21917
DRD2 GeneProduct uniprot:P14416
DRD1 GeneProduct ncbigene:568126
ADRA2C GeneProduct ncbigene:266752
ADRB3a GeneProduct ncbigene:558248
ADRA1B GeneProduct uniprot:P35368
ADRA2A GeneProduct ncbigene:266750
ADRB1 GeneProduct ncbigene:557194
ADRA2B GeneProduct ncbigene:266751
ADRA1D GeneProduct uniprot:P25100
ADRB2 GeneProduct uniprot:P07550
DLGAP5 GeneProduct uniprot:Q15398
DLGAP3 GeneProduct uniprot:O95886
DLGAP4 GeneProduct uniprot:Q9Y2H0
DLGAP2 GeneProduct uniprot:Q9P1A6
CTNNB1 GeneProduct ensembl:ENSG00000168036
DLGAP1 GeneProduct uniprot:O14490
Cortactin GeneProduct ensembl:ENSG00000085733
PSD95 GeneProduct uniprot:P78352
GKAP1 GeneProduct uniprot:Q5VSY0
PLCB GeneProduct uniprot:P50148
GAD2 GeneProduct uniprot:Q05329
GAD1 GeneProduct uniprot:Q99259
SLC6A1 GeneProduct uniprot:P30531
FMO3 GeneProduct uniprot:Q01740
CYP3A4 GeneProduct ensembl:ENSG00000160868
CYP2C19 GeneProduct ensembl:ENSG00000165841
ADCY1 GeneProduct uniprot:58165
CNR1 GeneProduct uniprot:P21554 CB1
CYP2C9 GeneProduct ensembl:ENSG00000138109
MAPK GeneProduct eccode:2.7.11.24
DAGLB GeneProduct ensembl:ENSG00000164535
ADCY7 GeneProduct uniprot:ADCY7
DAGLA GeneProduct ensembl:ENSG00000134780
FAAH GeneProduct ensembl:ENSG00000117480
ADORA2A GeneProduct uniprot:P29274
CNR2 GeneProduct uniprot:P34972 CB2
PRKACB GeneProduct ensembl:ENSG00000142875
PRKACA GeneProduct ensembl:ENSG00000072062
PRKAR1A GeneProduct ensembl:ENSG00000108946
PRKAR2B GeneProduct ensembl:ENSG00000005249
PRKAR1B GeneProduct ensembl:ENSG00000188191
PRKACG GeneProduct ensembl:ENSG00000165059
PRKAR2A GeneProduct ena.embl:ENSG00000114302
PIK3AP1 GeneProduct uniprot:Q6ZUJ8
AKT1 GeneProduct uniprot:P31749
PTEN GeneProduct uniprot:P60484 GPT4: The PTEN gene, known for its role in cell growth and survival, has a notable connection with Autism Spectrum Disorder (ASD) and a potential link to Attention Deficit Hyperactivity Disorder (ADHD): ASD and PTEN: Mutations in PTEN are associated with an increased risk of ASD. These mutations can lead to macrocephaly (an unusually large head) and disrupt the PI3K/AKT/mTOR pathway, crucial for brain development. This disruption may contribute to ASD development. ADHD and PTEN: The link between PTEN and ADHD is less established. While PTEN is involved in neural development, ADHD is primarily associated with neurotransmitter systems. The potential impact of PTEN on ADHD requires more research. Overall, PTEN is more clearly linked to ASD through its role in neural pathways, while its connection to ADHD is still under investigation.
'We have identified a distinct neuropsychological profile associated with mutations in PTEN suggesting primary disruption of frontal lobe systems21,22. Specifically, individuals with PTEN mutations showed reduced performance on measures of attention, impulsivity, reaction time, processing speed, and motor coordination, consistent with our pilot findings in independent patient cohorts19,20. This pattern of cognitive deficits may be related to neuroanatomical abnormalities. PTEN is a dual-specificity phosphatase that is a major inhibitor of the PI3K-AKT pathway23–25 with downstream effects on mTOR signaling, which helps regulate neural cell growth and proliferation26.' doi: 10.1038/s41398-019-0588-1
AKT2 GeneProduct uniprot:P31751
AKT3 GeneProduct uniprot:Q9Y243
PLCG2 GeneProduct uniprot:P16885
MLST8 GeneProduct ensembl:ENSG00000167965
AKT1S1 GeneProduct ensembl:ENSG00000204673
RPTOR GeneProduct ensembl:ENSG00000141564
DEPTOR GeneProduct ensembl:ENSG00000155792
MTOR GeneProduct ensembl:ENSG00000198793 effect of AKT on MTOR is indirect
Part of two multiprotein complexes, TORC 1 and TORC 2
MAPKAP1 GeneProduct ensembl:ENSG00000119487
RICTOR GeneProduct ensembl:ENSG00000164327
MECP2 GeneProduct ensembl:ENSG00000169057
linkages between MECP2, PTEN, PRKCB, mTORC1, mTORC2, and their relationship to ASD and Rett Syndrome, as well as the connection between Rett Syndrome and ASD at a biological pathway level: MECP2 and mTOR Pathway in Rett Syndrome: MECP2 mutations in Rett Syndrome can disrupt mTOR signaling. This affects neuronal development, synaptic formation, and plasticity, which are crucial for brain function. PTEN and ASD: PTEN is a gene that negatively regulates the mTOR pathway. Mutations in PTEN can lead to hyperactivation of mTOR, contributing to neurodevelopmental issues associated with ASD, including abnormal neuronal growth. PRKCB and mTOR in ASD: PRKCB influences the mTOR pathway. Its dysregulation in ASD can impact neuronal signaling and function, potentially leading to ASD-related neurological abnormalities. mTORC1 and mTORC2 in Both Disorders: Both mTORC1 and mTORC2 play key roles in neuronal health. In Rett Syndrome and ASD, the imbalance in these complexes' activities can lead to synaptic dysfunctions, altered neuron morphology, and cognitive and behavioral impairments. Common Biological Pathways in Rett Syndrome and ASD: Both disorders exhibit disruptions in the mTOR signaling pathway, affecting brain development and function. This includes impacts on neuron growth, synaptic plasticity, and brain connectivity, which are fundamental in both Rett Syndrome and ASD. In essence, both Rett Syndrome and ASD share a critical commonality in the dysregulation of the mTOR pathway and its impact on brain development and function. The genes MECP2, PTEN, and PRKCB all intersect with the mTOR pathway, influencing the development and severity of these neurodevelopmental disorders.
PRKAA2 GeneProduct uniprot:P54646
PIK3C3 GeneProduct ensembl:ENSG00000078142
ATG10 GeneProduct ensembl:ENSG00000152348
WIPI2 GeneProduct ensembl:ENSG00000157954
ATG7 GeneProduct ensembl:ENSG00000197548
ATG14 GeneProduct ensembl:ENSG00000126775
ATG13 GeneProduct ensembl:ENSG00000175224
RB1CC1 GeneProduct ensembl:ENSG00000023287
AMPK GeneProduct ensembl:ENSG00000132356
ULK1 GeneProduct ensembl:ENSG00000177169
ATG16L1 GeneProduct ensembl:ENSG00000085978
ATG12 GeneProduct ensembl:ENSG00000145782
BECN1 GeneProduct ensembl:ENSG00000126581
LC3 GeneProduct ensembl:ENSG00000101460
ATG2A GeneProduct ensembl:ENSG00000110046
LKB1 GeneProduct ensembl:ENSG00000118046
PIK3R4 GeneProduct ensembl:ENSG00000196455
ATG5 GeneProduct ensembl:ENSG00000057663
WIPI1 GeneProduct ensembl:ENSG00000070540
ATG4 GeneProduct ensembl:ENSG00000101844
WDR45 GeneProduct ensembl:ENSG00000196998
ATG101 GeneProduct ensembl:ENSG00000123395
ATG3 GeneProduct ensembl:ENSG00000144848
ACACA GeneProduct ensembl:ENSG00000278540
SESN2 GeneProduct uniprot:P58004
SLC25A39 GeneProduct uniprot:Q9BZJ4
SCN2A Protein uniprot:Q99250
TP53 Protein dbsnp:P04637
RHOA Protein uniprot:P61586
INSR Protein uniprot:P06213
NGLY1 Protein uniprot:Q96IV0 PNG hydrolase, PNGH
ALPI Protein uniprot:P09923 Intestinal-type alkaline phosphatase
RHEB Protein uniprot:Q15382
AOX1 Protein uniprot:Q06278 Aldehyde oxidase
PDGFRA Protein uniprot:P16234
EGFR Protein uniprot:P00533
KIT Protein uniprot:P10721
MAPK1 Protein dbsnp:P28482
SCN1A Protein uniprot:P35498
ALDH2 Protein uniprot:P05091
NOX4 Protein uniprot:Q9NPH5
SCN4B Protein uniprot:Q8IWT1
ADAM10 Protein uniprot:O14672
GABRA2 Protein uniprot:P47869
PCBD1 Protein uniprot:P61457
PCBD2 Protein uniprot:Q9H0N5
SLC25A32 Protein uniprot:Q9H2D1
AANAT Protein uniprot:Q16613
SCN5A Protein uniprot:Q14524
MAOA Protein uniprot:P21397
TY Protein uniprot:P07101
CSAD Protein uniprot:Q9Y600
PTS Protein uniprot:Q03393
GABRB3 Protein uniprot:P28472
MAOB Protein uniprot:P27338
CBS Protein uniprot:P35520
GABRA3 Protein uniprot:P34903
GABRA5 Protein uniprot:P31644
SLC18A2 Protein uniprot:P23975 The SLC18A2 gene encodes the vesicular monoamine transporter 2 (VMAT2), which is primarily involved in the transport of various monoamine neurotransmitters into synaptic vesicles. The types of neurotransmitters that use VMAT2 for vesicular transport include: Primary Neurotransmitters Transported by VMAT2 Dopamine Function: Dopamine is essential for reward, motivation, motor control, and various other brain functions. It plays a critical role in conditions like Parkinson's disease, schizophrenia, and addiction. Transport: VMAT2 is the primary transporter for loading dopamine into synaptic vesicles in dopaminergic neurons. Norepinephrine (Noradrenaline) Function: Norepinephrine is involved in attention, arousal, and the fight-or-flight response. Transport: VMAT2 is responsible for transporting norepinephrine into vesicles in noradrenergic neurons. Serotonin (5-HT) Function: Serotonin regulates mood, appetite, sleep, and other functions. It is crucial in the pathophysiology of depression and anxiety disorders. Transport: VMAT2 also transports serotonin into synaptic vesicles in serotonergic neurons. Histamine Function: Histamine plays a role in sleep-wake regulation, immune responses, and gastric acid secretion. Transport: VMAT2 transports histamine into vesicles in histaminergic neurons. Additional Role of VMAT2 VMAT2 is known for its broad specificity and efficiency in transporting monoamines into synaptic vesicles across different types of monoaminergic neurons. This makes it a key transporter for various critical neurotransmitters involved in multiple neurophysiological processes. Summary VMAT2 (encoded by SLC18A2) is the primary vesicular transporter for several key monoamine neurotransmitters, including dopamine, norepinephrine, serotonin, and histamine. It is predominantly used in dopaminergic, noradrenergic, serotonergic, and histaminergic neurons to load these neurotransmitters into synaptic vesicles, facilitating their storage and release during synaptic transmission.
GLS Protein uniprot:O94925
SLC46A1 Protein uniprot:Q96NT5
CPLX1 Protein uniprot:O14810
SHMT2 Protein uniprot:P34897
OPRM1 Protein uniprot:P35372
CYP2D6 Protein uniprot:P10635
SCN10A Protein uniprot:Q9Y5Y9
ALDH5A1 Protein uniprot:57706
SULT1A3 Protein uniprot:P0DMM9
SLC25A12 Protein uniprot:O75746
MTRR Protein uniprot:Q9UBK8
PNPO Protein uniprot:Q9NVS9
SCN7A Protein uniprot:Q01118
HISN8 Protein uniprot:Q9C5U8
NADSYN1 Protein uniprot:Q6IA69
MTHFD2L Protein uniprot:Q9H903
RFK Protein uniprot:Q969G6
DBH Protein uniprot:P09172
GABRA1 Protein uniprot:P14867
SCN8A Protein uniprot:Q9UQD0
SLC19A1 Protein uniprot:P41440
NOS1 Protein uniprot:P29475
PNMT Protein uniprot:P11086
GABRA4 Protein uniprot:P48169
AKR1B1 Protein uniprot:P15121
BHMT Protein uniprot:Q93088
DHFR Protein uniprot:P00374
GABRB1 Protein uniprot:P18505
QPRT Protein uniprot:Q15274
SOD2 Protein uniprot:P04179
SCN2B Protein uniprot:O60939
SCN9A Protein uniprot:Q15858
GABRG1 Protein uniprot:Q8N1C3
SLC6A4 Protein uniprot:P31645
GABRG2 Protein uniprot:P18507
ADGRL3GPCRs Protein uniprot:Q9HAR2
GABRQ Protein uniprot:Q9UN88
SCN3B Protein uniprot:Q9NY72
NOX1 Protein uniprot:Q9Y5S8
GABRB2 Protein uniprot:P47870
SLC6A2 Protein uniprot:P23975 The SLC6A2 gene encodes the norepinephrine transporter (NET), which plays a crucial role in the reuptake of norepinephrine (noradrenaline) from the synaptic cleft back into the presynaptic neuron. Here are the key functions and details about SLC6A2 and NET: Key Functions of NET (SLC6A2) Reuptake of Norepinephrine: Primary Function: NET is responsible for the high-affinity reuptake of norepinephrine from the synaptic cleft into the presynaptic neuron. This process is essential for terminating norepinephrine signaling and regulating its concentration in the synaptic cleft. Mechanism: NET transports norepinephrine along with sodium and chloride ions across the plasma membrane of the presynaptic neuron. Recycling of Norepinephrine: Recycling: Once inside the presynaptic neuron, norepinephrine can be repackaged into synaptic vesicles by vesicular monoamine transporters (such as VMAT2) for future release. Regulation of Noradrenergic Signaling: Signal Termination: By removing norepinephrine from the synaptic cleft, NET helps terminate the noradrenergic signal, thereby regulating the duration and intensity of norepinephrine's effects on postsynaptic receptors. Homeostasis: NET helps maintain the homeostasis of norepinephrine levels in the synaptic cleft and prevents overstimulation of noradrenergic receptors. Clinical Relevance Neuropsychiatric Disorders: Depression and Anxiety: Dysregulation of NET function is implicated in mood disorders such as depression and anxiety. Certain antidepressants, such as tricyclic antidepressants and selective norepinephrine reuptake inhibitors (NRIs), target NET to increase norepinephrine levels in the synaptic cleft. Attention-Deficit/Hyperactivity Disorder (ADHD): NET is also a target for medications used to treat ADHD, such as atomoxetine, which increases norepinephrine availability by inhibiting its reuptake. Cardiovascular Regulation: Blood Pressure and Heart Rate: NET also plays a role in the autonomic nervous system, influencing cardiovascular functions by regulating norepinephrine levels in sympathetic neurons. Expression and Localization Expression Sites: NET is primarily expressed in noradrenergic neurons in the central and peripheral nervous systems, including the locus coeruleus in the brain, which is a major site of norepinephrine production. Peripheral Role: In the peripheral nervous system, NET is found in sympathetic neurons, where it regulates norepinephrine levels involved in the fight-or-flight response. Summary SLC6A2 encodes the norepinephrine transporter (NET), which is essential for the reuptake and recycling of norepinephrine from the synaptic cleft back into presynaptic neurons. This transporter plays a critical role in terminating noradrenergic signaling, maintaining neurotransmitter homeostasis, and regulating various physiological and psychological processes. Dysregulation of NET is associated with several neuropsychiatric disorders, and it is a target for various pharmacological treatments.
GCH1 Protein uniprot:P30793
FOLR1 Protein uniprot:P15328
MTHFD2 Protein uniprot:P13995
SLC6A3 Protein uniprot:Q01959 Sodium-dependent dopamine transporter, DA transporter, DAT, Solute carrier family 6 member 3. AKA DAT1
STXBP1 Protein uniprot:P61764
QDPR Protein uniprot:P09417
TAAR1 Protein uniprot:Q96RJ0
TYMS Protein uniprot:P04818
SCN1B Protein uniprot:Q07699
NOX3 Protein uniprot:Q9HBY0
DNMT1 Protein uniprot:P26358
TCN2 Protein uniprot:P20062
AGTR1 Protein uniprot:P30556
NOS3 Protein uniprot:P29474
SCN4A Protein uniprot:P35499
MOCOS Protein uniprot:Q96EN8
PAH Protein uniprot:P00439
GABRD Protein uniprot:O14764
AGMO Protein uniprot:Q6ZNB7
ASMT Protein uniprot:P46597
DDC Protein uniprot:P20711
SOD1 Protein uniprot:P00441
NCAM1 Protein uniprot:P13591
RIT2 Protein uniprot:Q99578
TPH2 Protein uniprot:Q8IWU9
MTR Protein uniprot:Q99707
MTHFR Protein uniprot:P42898
NMNAT1 Protein uniprot:Q9HAN9
SCN11A Protein uniprot:Q9UI33
SLC25A13 Protein uniprot:Q9UJS0
ALDH1L1 Protein uniprot:O75891
SCN3A Protein uniprot:Q9NY46
GPHN Protein uniprot:Q9NQX3
NOX5 Protein uniprot:Q96PH1
SLC17A7 Protein uniprot:Q9P2U8 Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, proton, potassium, sodium and phosphate (PubMed:10820226). At the synaptic vesicle membrane, mainly functions as an uniporter which transports preferentially L-glutamate but also phosphate from the cytoplasm into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells (By similarity).
KYAT3 Protein uniprot:Q6YP21
ALDH1L2 Protein uniprot:Q3SY69
GK Protein uniprot:P32189
SYP Protein uniprot:P08247
REN Protein uniprot:P00797
CTH Protein uniprot:P32929
AHCY Protein uniprot:P23526
SPR Protein uniprot:P35270
TPH1 Protein uniprot:P17752
ADH Protein kegg.genes:EC 1.1.1.1
MAT1A Protein uniprot:Q00266
MAT2B Protein uniprot:Q9NZL9
AKR1A1 Protein uniprot:P14550
AKR1C3 Protein uniprot:P42330
CBR1 Protein uniprot:P16152
AKR1C1 Protein uniprot:Q04828
SHMT1 Protein uniprot:P34896
MTHFD1 Protein uniprot:P11586
MTHFD1L Protein uniprot:Q6UB35
NOS2 Protein uniprot:P35228
DRD5 Protein uniprot:P21918
HTR4 Protein uniprot:Q13639
HTR6 Protein uniprot:P50406
HTR1D Protein uniprot:P28221
HTR1E Protein uniprot:P28566
HTR7 Protein uniprot:P34969
HTR2A Protein uniprot:P28223
HTR1F Protein uniprot:P30939
HTR5a Protein ncbigene:100038775
HTR2B Protein uniprot:P41595
HTR1A Protein ncbigene:100001828
HTR1B Protein ncbigene:561647
ADRA1A Protein uniprot:P35348
COMT Protein uniprot:P21964 AKA Catechol-O- metyltransferase
SNAP25 Protein uniprot:P60880
VAMP2 Protein uniprot:P63027
SYT1 Protein uniprot:P21579
STX1A Protein uniprot:Q16623
GRM8 Protein uniprot:O00222
KCNA2 Protein uniprot:P16389
KCNA1 Protein uniprot:Q09470
DLG3 Protein uniprot:Q92796
GRM6 Protein uniprot:O15303
GRM5 Protein uniprot:P41594
GRM3 Protein uniprot:Q14832
KCNA3 Protein uniprot:P22001
GRIN2C Protein uniprot:Q14957
DLG5 Protein uniprot:Q8TDM6
GRM4 Protein uniprot:Q14833
GRIN2B Protein uniprot:Q13224
GRIA1 Protein uniprot:P42261
GRIN1 Protein uniprot:Q05586
GRM2 Protein uniprot:Q14416
GRIN2A Protein uniprot:Q12879
KCNA4 Protein uniprot:P22459
KCNA5 Protein uniprot:P22460
DLG2 Protein uniprot:Q15700
KCNA6 Protein uniprot:P17658
GRIA2 Protein uniprot:P42262
GRM7 Protein uniprot:Q14831
OXTR Protein uniprot:P30559
MC4R Protein uniprot:P32245
SHANK1 Protein uniprot:Q9Y566
GRIA4 Protein uniprot:P48058
NLGN1 Protein uniprot:Q8N2Q7
NRXN2 Protein uniprot:P58401
GRIN3B Protein uniprot:O60391
ABL1 Protein uniprot:P00519
HOMER2 Protein uniprot:Q9NSB8
GRIN3A Protein uniprot:Q8TCU5
DLG4 Protein uniprot:P78352
NLGN2 Protein uniprot:Q8NFZ4
KCNA7 Protein uniprot:Q96RP8
CBL Protein uniprot:P22681
SRBS2 Protein uniprot:O94875
GRIN2D Protein uniprot:O15399
NLGN4X Protein uniprot:Q8N0W4
NRXN3 Protein uniprot:Q9HDB5
APP Protein uniprot:P05067
SHANK3 Protein uniprot:Q9BYB0
GRIA3 Protein uniprot:P42263
GRIP2 Protein uniprot:Q9C0E4
HOMER3 Protein uniprot:Q9NSC5
DLG1 Protein uniprot:Q12959
NRXN1 Protein uniprot:Q9ULB1
NLGN3 Protein uniprot:Q9NZ94
PTK2B Protein uniprot:Q14289
HOMER1 Protein uniprot:Q86YM7
SHANK2 Protein uniprot:Q9UPX8
GRM1 Protein uniprot:Q13255
GRIP1 Protein uniprot:Q9Y3R0
CACNG2 Protein uniprot:Q9Y698
CTTN Protein uniprot:Q14247
ABL2 Protein uniprot:P42684
FOLR2 Protein uniprot:P14207
HTR3A Protein uniprot:P40227
HTR3B Protein uniprot:O95264
HTR3C Protein uniprot:Q8WXA8
HTR3D Protein uniprot:Q70Z44
HTR3E Protein uniprot:A5X5Y0
CACNG6 Protein uniprot:Q9BXT2
CACNG7 Protein uniprot:P62955
CACNG3 Protein uniprot:O60359
CACNG4 Protein uniprot:Q9UBN1
CACNG8 Protein uniprot:Q8WXS5
CACNG5 Protein uniprot:Q9UF02
CACNG1 Protein uniprot:Q06432
GNAQ Protein uniprot:P50148
OXT Protein uniprot:P01178
CACNA1C Protein uniprot:Q13936
SOD3 Protein uniprot:P08294
IFNG Protein uniprot:P01579
KYNU Protein uniprot:Q16719
KAT1 Protein uniprot:Q16773
KMO Protein uniprot:O15229
IDO1 Protein uniprot:P14902
IDO2 Protein uniprot:Q6ZQW0
T23O Protein uniprot:P48775
KAT3 Protein uniprot:Q6YP21
AADAT Protein uniprot:Q8N5Z0
AATM Protein uniprot:P00505
TNFA Protein uniprot:P01375
GABBR1 Protein uniprot:Q9UBS5
SLC32A1 Protein uniprot:Q9H598 Vesicular inhibitory amino acid transporter
ALDH9A1 Protein uniprot:P49189 4-trimethylaminobutyraldehyde dehydrogenase
ABAT Protein uniprot:P80404 4-Aminobutyrate aminotransferase
GLS2 Protein uniprot:Q9UI32
ABCD4 Protein uniprot:O14678 cblJ
MMUT Protein uniprot:P22033 aka methylmalonyl-CoA mutase or MCM
CD320 Protein uniprot:Q9NPF0 Aka CD320 receptor
cbLAMMAA Protein uniprot:Q8IVH4 Gene: MMAA
LMBRD1 Protein uniprot:Q9NUN5 cblF
MMACHC Protein uniprot:Q9Y4U1 cbLC
MMAB Protein uniprot:60488 cblB
MMADHC Protein uniprot:Q9H3L0 'cblD protein might be responsible for branching of the cobalamin metabolism pathways to the cytosolic or mitochondrial compartments' Pubmed: 21114891
gene is called MMADHC
NAPEPLD Protein uniprot:NAPEPLD
TSC1 Protein uniprot:Q92574
TSC2 Protein uniprot:P49815
PIK3R2 Protein uniprot:O00459
PIK3CB Protein uniprot:P42338
PIK3CA Protein uniprot:P42336
PIK3R1 Protein uniprot:P27986
PIK3CD Protein uniprot:O00329
PIK3R3 Protein uniprot:Q92569
PDGFRB Protein uniprot:P09619
PRKCD Protein uniprot:Q05655
PRKCZ Protein uniprot:Q05513
PRKCA Protein uniprot:P17252
PRKCB Protein uniprot:P05771
PRKCG Protein uniprot:P05129
MAPK3 Protein dbsnp:P27361
MMACHC Protein uniprot:Q9Y4U1 Gene is called MMAC
MMAA Protein uniprot:Q8IVH4 cbLA
TCN2 Protein uniprot:P20062 aka Transcobalamin 2
TCN1 Protein uniprot:P20061 aka haptocorrin or transcobalamin 1
Produced in saliva and stomach
CUBN Protein uniprot:O60494 aka cubilin
TCN1 Protein uniprot:P20061 aka haptocorrin or transcobalamin 1
CBLIF Protein uniprot:P27352 aka (gastric) intrinsic factor, transcobalamin III
Located in gastric parietal cells
CBLIF Protein uniprot:P27352 aka intrinsic factor
AMN Protein uniprot:Q9BXJ7 aka amnionless
PDXK Protein uniprot:O00764
ALPL Protein uniprot:P05186
GNMT Protein uniprot:Q14749
APRT Protein uniprot:P07741
ATIC Protein uniprot:P31939
ADA Protein uniprot:P00813 aka Adenosine deaminase
ADSS Protein uniprot:P30520 Adenylosuccinate synthetase isozyme 2
ADSL Protein uniprot:P30566
IMPDH1 Protein uniprot:P20839
HPRT1 Protein uniprot:P00492
DGUOK Protein uniprot:Q16854
AMPD1 Protein uniprot:P23109
ITPA Protein uniprot:Q9BY32
RR Protein eccode:1.17.4.1 ribonucleotide reductase
PNP Protein uniprot:P00491
XO Protein uniprot:P47989
SLC25A40 Protein uniprot:Q8TBP6
SLC18A1 Protein uniprot:P54219 The SLC18A1 gene encodes the vesicular monoamine transporter 1 (VMAT1), which is primarily involved in the transport of specific monoamine neurotransmitters into synaptic vesicles. The types of neurotransmitters that use VMAT1 for vesicular transport include: Primary Neurotransmitters Transported by VMAT1 Serotonin (5-HT) Function: Serotonin is involved in regulating mood, appetite, sleep, and other functions. It plays a key role in the pathophysiology of depression and anxiety disorders. Transport: VMAT1 loads serotonin into synaptic vesicles in serotonergic neurons. Histamine Function: Histamine is involved in the regulation of sleep-wake cycles, immune responses, and gastric acid secretion. Transport: VMAT1 transports histamine into vesicles primarily in histaminergic neurons. Secondary Neurotransmitters Transported by VMAT1 (to a lesser extent) Dopamine Function: Dopamine is crucial for reward, motivation, motor control, and several other functions. Dysregulation is associated with Parkinson's disease, schizophrenia, and addiction. Transport: While VMAT1 can transport dopamine, it does so less efficiently compared to VMAT2. Dopaminergic neurons predominantly rely on VMAT2. Norepinephrine (Noradrenaline) Function: Norepinephrine is involved in attention, arousal, and the fight-or-flight response. Transport: Similar to dopamine, VMAT1 can transport norepinephrine but with lower efficiency compared to VMAT2. Noradrenergic neurons primarily use VMAT2. Summary VMAT1 (encoded by SLC18A1) primarily transports serotonin and histamine into synaptic vesicles, playing a key role in serotonergic and histaminergic neurotransmission. It also has the capacity to transport dopamine and norepinephrine, although these functions are predominantly handled by VMAT2 (encoded by SLC18A2) in dopaminergic and noradrenergic neurons, respectively.

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