Congenital generalized lipodystrophy (WP5101)

Homo sapiens

Open in new tab Open in NDEx Open in Newt (SBGN)
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads
Congenital generalized lipodystrophy (CGL) is divided into four subtypes. Type 1 is mainly caused by mutations in AGPAT2 gene, subtype 2 by BSCL2 mutations, type 3 by CAV1 mutations and type 4 by CAVIN1 mutations. Patients with CGL show a near total absence of body fat which starts either at birth or shortly after. There are also metabolic abnormalities. Type 1 CGL shows loss of metabolically active adipose tissue. Type 2 CGL has a general absence of adipose tissue. Patients with type 3 CGL show vitamin D resistance, hypocalcemia, hypomagnesemia and have a short stature. Patients with type 4 CGL show myopathy, skeletal abnormalities, cardiac arrhythmias, pyloric stenosis and gastrointestinal motility problems.

Authors

Ulas Babayigit , Eric Weitz , Friederike Ehrhart , and Egon Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Rare Diseases

Annotations

Disease Ontology

congenital generalized lipodystrophy type 4 congenital generalized lipodystrophy congenital generalized lipodystrophy type 1 congenital generalized lipodystrophy type 2 congenital generalized lipodystrophy type 3

Pathway Ontology

disease pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Triacylglycerol Metabolite chebi:17855
Phosphatidic acid Metabolite chebi:16337
Diacylglycerol Metabolite chebi:85682
Lysophosphatidic acid Metabolite chembl.compound:ChEMBL117021
IRS1 GeneProduct ensembl:ENSG00000169047
DGAT2 GeneProduct ensembl:ENSG00000062282
PI3K GeneProduct ensembl:ENSG00000121879
DGAT1 GeneProduct ensembl:ENSG00000185000
GPAT3 GeneProduct ensembl:ENSG00000138678
AKT2 GeneProduct ensembl:ENSG00000105221
ITGB4 GeneProduct ensembl:ENSG00000132470
GRB2 GeneProduct ensembl:ENSG00000177885
HIF1A GeneProduct ensembl:ENSG00000100644
CAV1 GeneProduct ensembl:ENSG00000105974
BSCL2 GeneProduct ensembl:ENSG00000168000
FYN GeneProduct ensembl:ENSG00000010810
CAVIN1 GeneProduct ensembl:ENSG00000177469 Also known as PTRF
AGPAT2 GeneProduct ensembl:ENSG00000169692
CAVIN1 GeneProduct ensembl:ENSG00000177469
LPIN3 GeneProduct ensembl:ENSG00000132793
LPIN2 GeneProduct ensembl:ENSG00000101577
LPIN1 GeneProduct ensembl:ENSG00000134324
INS Protein ensembl:ENSG00000254647 Insulin
Seipin Protein uniprot:F8WER0 Protein of BSCL2
Glycerol-3-phosphate Protein uniprot:A0A024R8I7

References

  1. A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Wary KK, Mariotti A, Zurzolo C, Giancotti FG. Cell. 1998 Sep 4;94(5):625–34. PubMed Europe PMC Scholia
  2. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EWT, Chang F, et al. Biochim Biophys Acta. 2007 Aug;1773(8):1263–84. PubMed Europe PMC Scholia
  3. Insulin signalling mechanisms for triacylglycerol storage. Czech MP, Tencerova M, Pedersen DJ, Aouadi M. Diabetologia. 2013 May;56(5):949–64. PubMed Europe PMC Scholia
  4. Congenital generalized lipodystrophies--new insights into metabolic dysfunction. Patni N, Garg A. Nat Rev Endocrinol. 2015 Sep;11(9):522–34. PubMed Europe PMC Scholia
  5. Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway. Xu L, Wang L, Wen Z, Wu L, Jiang Y, Yang L, et al. Am J Physiol Cell Physiol. 2016 Jun 1;310(11):C903-10. PubMed Europe PMC Scholia
  6. AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue. Cautivo KM, Lizama CO, Tapia PJ, Agarwal AK, Garg A, Horton JD, et al. Mol Metab. 2016 May 13;5(7):491–505. PubMed Europe PMC Scholia
  7. Caveolin-1 in the regulation of cell metabolism: a cancer perspective. Nwosu ZC, Ebert MP, Dooley S, Meyer C. Mol Cancer. 2016 Nov 16;15(1):71. PubMed Europe PMC Scholia
  8. Seipin regulates ER-lipid droplet contacts and cargo delivery. Salo VT, Belevich I, Li S, Karhinen L, Vihinen H, Vigouroux C, et al. EMBO J. 2016 Dec 15;35(24):2699–716. PubMed Europe PMC Scholia
  9. Genetics of Lipodystrophy. Lightbourne M, Brown RJ. Endocrinol Metab Clin North Am. 2017 Jun;46(2):539–54. PubMed Europe PMC Scholia
  10. Two Glycerol-3-Phosphate Dehydrogenases from Chlamydomonas Have Distinct Roles in Lipid Metabolism. Driver T, Trivedi DK, McIntosh OA, Dean AP, Goodacre R, Pittman JK. Plant Physiol. 2017 Aug;174(4):2083–97. PubMed Europe PMC Scholia
  11. Expression of AGPAT2, an enzyme involved in the glycerophospholipid/triacylglycerol biosynthesis pathway, is directly regulated by HIF-1 and promotes survival and etoposide resistance of cancer cells under hypoxia. Triantafyllou EA, Georgatsou E, Mylonis I, Simos G, Paraskeva E. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Sep;1863(9):1142–52. PubMed Europe PMC Scholia
  12. Lipodystrophy Syndromes: Presentation and Treatment. Akinci B, Sahinoz M, Oral E. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2018. PubMed Europe PMC Scholia
  13. Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis. Machado-Neto JA, Fenerich BA, Rodrigues Alves APN, Fernandes JC, Scopim-Ribeiro R, Coelho-Silva JL, et al. Clinics (Sao Paulo). 2018 Oct 11;73(suppl 1):e566s. PubMed Europe PMC Scholia
  14. Cavin-1/PTRF mediates insulin-dependent focal adhesion remodeling and ameliorates high-fat diet-induced inflammatory responses in mice. Wang H, Pilch PF, Liu L. J Biol Chem. 2019 Jul 5;294(27):10544–52. PubMed Europe PMC Scholia
  15. The biogenesis of lipid droplets: Lipids take center stage. Gao M, Huang X, Song BL, Yang H. Prog Lipid Res. 2019 Jul;75:100989. PubMed Europe PMC Scholia
  16. LDAF1 and Seipin Form a Lipid Droplet Assembly Complex. Chung J, Wu X, Lambert TJ, Lai ZW, Walther TC, Farese RV Jr. Dev Cell. 2019 Dec 2;51(5):551-563.e7. PubMed Europe PMC Scholia
  17. Oligomers of the lipodystrophy protein seipin may co-ordinate GPAT3 and AGPAT2 enzymes to facilitate adipocyte differentiation. Sim MFM, Persiani E, Talukder MMU, Mcilroy GD, Roumane A, Edwardson JM, et al. Sci Rep. 2020 Feb 24;10(1):3259. PubMed Europe PMC Scholia
  18. Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy. Song L, Liu Z, Hu HH, Yang Y, Li TY, Lin ZZ, et al. Nat Commun. 2020 Nov 17;11(1):5842. PubMed Europe PMC Scholia