Details of Disease

General Information of Disease (ID: DIS3SGVD)

• Disease Name: Lipodystrophy
• Synonyms: lipodsystrophic syndrome; lipodystrophy (disease); lipodystrophy; lipodsystrophic syndromes
• Disease Class: EF01: Lipoatrophy/lipodystrophy
• Definition: A congenital or acquired disorder characterized by abnormal loss or redistribution of the adipose tissue in the body.
• Disease Hierarchy:
  DIS71G5H: Metabolic disorder
  DISWD40R: Disease
  DIS9YPUQ: Dermatological disease
  DIS3SGVD: Lipodystrophy
• ICD Code:
  ICD-11: ICD-11: EF01
  ICD-10: ICD-10: E88.1
  ICD-9: ICD-9: 272.6
  Expand ICD-11: 'EF01
  Expand ICD-10: 'E88.1
  Expand ICD-9: 272.6
• Disease Identifiers:
  MONDO ID: MONDO_0006573
  MESH ID: D008060
  UMLS CUI: C0023787
  MedGen ID: 6111
  HPO ID: HP:0009125
  SNOMED CT ID: 71325002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
AKL-0707	DME6OXB	Discontinued in Phase 2	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 24 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADRA2A	TTWG9A4	Limited	Autosomal dominant	[2]
ADIPOQ	TTXKA7D	moderate	Genetic Variation	[3]
DAPK3	TTERVQN	moderate	Biomarker	[4]
KCNJ6	TTTIBVP	moderate	Genetic Variation	[5]
SREBF1	TTER0UB	moderate	Genetic Variation	[6]
AGPAT1	TTPL1TK	Strong	Genetic Variation	[7]
AGPAT2	TT9AYVR	Strong	Biomarker	[8]
AKT2	TTH24WI	Strong	Genetic Variation	[9]
ANGPTL3	TT59GO7	Strong	Altered Expression	[10]
APOC3	TTXOZQ1	Strong	Genetic Variation	[11]
CACNA1S	TT94HRF	Strong	Genetic Variation	[12]
CAV1	TTXUBN2	Strong	Genetic Variation	[13]
FSHB	TT13GFV	Strong	Altered Expression	[14]
FSHR	TTZFDBT	Strong	Altered Expression	[14]
GMNN	TT390KA	Strong	Genetic Variation	[15]
IGF1R	TTQFBMY	Strong	Biomarker	[16]
PARP2	TTQ4V96	Strong	Biomarker	[17]
PDGFRB	TTI7421	Strong	Genetic Variation	[18]
PPARG	TTT2SVW	Strong	Genetic Variation	[19]
PSMB8	TTEAD9J	Strong	Genetic Variation	[20]
SLC28A2	TTVP9IQ	Strong	Genetic Variation	[21]
STAB2	TTM3DAY	Strong	Biomarker	[22]
WRN	TT2H5WQ	Strong	Genetic Variation	[23]
FGF21	TTQ916P	Definitive	Altered Expression	[24]

This Disease Is Related to 4 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC16A2	DTQ8MP1	Strong	Altered Expression	[25]
SLC28A1	DT0EQPW	Strong	Genetic Variation	[21]
SLC28A3	DT4YL5R	Strong	Genetic Variation	[21]
SLC29A2	DTW78DQ	Strong	Genetic Variation	[21]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PCK1	DEPLH5Z	Strong	Genetic Variation	[26]

This Disease Is Related to 27 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADRA2A	OTZFGOTP	Limited	Autosomal dominant	[2]
BSCL2	OT73V6Y4	Limited	Genetic Variation	[27]
CAVIN1	OTFO915U	Limited	Genetic Variation	[28]
FBN1	OTYCJT63	Limited	Biomarker	[29]
POLD1	OTWO4UCJ	Limited	Genetic Variation	[30]
AGL	OTWBM7WY	moderate	Genetic Variation	[31]
CNBP	OTTGM9NK	moderate	Biomarker	[32]
LMNB2	OTXRDUOS	moderate	Genetic Variation	[33]
ARL15	OT00YSWZ	Strong	Biomarker	[34]
CIDEC	OTMDZ56K	Strong	Biomarker	[35]
CNOT3	OT4D5Z9L	Strong	Biomarker	[36]
DIO2	OTGPNSLH	Strong	Altered Expression	[25]
DLGAP1	OTF2PUUI	Strong	Genetic Variation	[37]
EMD	OTR8ZANE	Strong	Genetic Variation	[38]
FERMT2	OTZNPWWX	Strong	Altered Expression	[39]
FITM2	OTED0W1S	Strong	Biomarker	[40]
IFIH1	OTZA2AHA	Strong	Biomarker	[41]
LHB	OT5GBOVJ	Strong	Altered Expression	[14]
LMF1	OTOL14ZD	Strong	Biomarker	[42]
LPIN2	OTRRTMXX	Strong	Biomarker	[43]
METTL9	OT3YR9B2	Strong	Biomarker	[44]
PDAP1	OTJSWMOD	Strong	Biomarker	[44]
PIK3R1	OT5BZ1J9	Strong	Biomarker	[45]
REEP1	OTEMVFX7	Strong	Genetic Variation	[46]
RP9	OTGQY66H	Strong	Biomarker	[44]
TCP1	OT1MGUX9	Strong	Genetic Variation	[47]
EBF1	OTZ61YYH	Definitive	Biomarker	[48]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021539)
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Lower serum adiponectin level is associated with lipodystrophy among HIV-infected men in the Study toUnderstand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) study.HIV Med. 2019 Sep;20(8):534-541. doi: 10.1111/hiv.12754. Epub 2019 May 31.
• [4] A search for candidate genes for lipodystrophy, obesity and diabetes via gene expression analysis of A-ZIP/F-1 mice.Genomics. 2003 Apr;81(4):378-90. doi: 10.1016/s0888-7543(03)00024-7.
• [5] Gain-of-function KCNJ6 Mutation in a Severe Hyperkinetic Movement Disorder Phenotype.Neuroscience. 2018 Aug 1;384:152-164. doi: 10.1016/j.neuroscience.2018.05.031. Epub 2018 May 29.
• [6] LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations.Biochem Soc Trans. 2011 Dec;39(6):1752-7. doi: 10.1042/BST20110675.
• [7] Prevalence of mutations in AGPAT2 among human lipodystrophies.Diabetes. 2003 Jun;52(6):1573-8. doi: 10.2337/diabetes.52.6.1573.
• [8] Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2-/-) or obese (ob/ob) mice.J Lipid Res. 2016 Apr;57(4):616-30. doi: 10.1194/jlr.M065896. Epub 2016 Feb 15.
• [9] Analysis of genetic variation in Akt2/PKB-beta in severe insulin resistance, lipodystrophy, type 2 diabetes, and related metabolic phenotypes.Diabetes. 2007 Mar;56(3):714-9. doi: 10.2337/db06-0921.
• [10] Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with generalized lipodystrophy.J Clin Lipidol. 2017 Mar-Apr;11(2):543-550. doi: 10.1016/j.jacl.2017.02.002. Epub 2017 Feb 24.
• [11] Polymorphisms in Fas gene is associated with HIV-related lipoatrophy in Thai patients.AIDS Res Hum Retroviruses. 2013 Jan;29(1):142-50. doi: 10.1089/AID.2012.0114. Epub 2012 Aug 20.
• [12] A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome.PLoS One. 2015 Jul 15;10(7):e0131797. doi: 10.1371/journal.pone.0131797. eCollection 2015.
• [13] Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome.Am J Med Genet A. 2015 Aug;167A(8):1796-806. doi: 10.1002/ajmg.a.37115. Epub 2015 Apr 21.
• [14] Leptin restores markers of female fertility in lipodystrophy.Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3292-3297. doi: 10.1016/j.bbadis.2018.07.015. Epub 2018 Jul 23.
• [15] De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. Am J Hum Genet. 2015 Dec 3;97(6):904-13. doi: 10.1016/j.ajhg.2015.11.006.
• [16] Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli type, express normal insulin receptors.Diabetologia. 1993 Feb;36(2):172-4. doi: 10.1007/BF00400701.
• [17] 5-Benzamidoisoquinolin-1-ones and 5-(-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2).J Med Chem. 2011 Apr 14;54(7):2049-59. doi: 10.1021/jm1010918. Epub 2011 Mar 18.
• [18] A tyrosine kinase-activating variant Asn666Ser in PDGFRB causes a progeria-like condition in the severe end of Penttinen syndrome.Eur J Hum Genet. 2019 Apr;27(4):574-581. doi: 10.1038/s41431-018-0323-z. Epub 2018 Dec 20.
• [19] Gene-gene and gene-environment interactions in lipodystrophy: Lessons learned from natural PPAR mutants.Biochim Biophys Acta Mol Cell Biol Lipids. 2019 May;1864(5):715-732. doi: 10.1016/j.bbalip.2019.02.002. Epub 2019 Feb 8.
• [20] Mutations in proteasome subunit type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity.Arthritis Rheum. 2012 Mar;64(3):895-907. doi: 10.1002/art.33368.
• [21] Altered expression of nucleoside transporter genes (SLC28 and SLC29) in adipose tissue from HIV-1-infected patients.Antivir Ther. 2007;12(6):853-63.
• [22] Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue.Mol Cell Biol. 2012 Dec;32(23):4794-810. doi: 10.1128/MCB.00512-12. Epub 2012 Oct 1.
• [23] Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome.Orphanet J Rare Dis. 2013 Jul 12;8:106. doi: 10.1186/1750-1172-8-106.
• [24] Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.PLoS One. 2013;8(3):e55632. doi: 10.1371/journal.pone.0055632. Epub 2013 Mar 22.
• [25] Regional decrease of subcutaneous adipose tissue in patients with type 2 familial partial lipodystrophy is associated with changes in thyroid hormone metabolism.Thyroid. 2010 Apr;20(4):419-24. doi: 10.1089/thy.2009.0267.
• [26] PCK1 and PCK2 as candidate diabetes and obesity genes.Cell Biochem Biophys. 2007;48(2-3):89-95. doi: 10.1007/s12013-007-0025-6.
• [27] Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant.Neurogenetics. 2019 May;20(2):73-82. doi: 10.1007/s10048-019-00574-5. Epub 2019 Mar 23.
• [28] Interaction of cavin-1/PTRF leucine zipper domain 2 and its congenitalgeneralizedlipodystrophy mutant with model membranes.Biochem Biophys Res Commun. 2020 Jan 15;521(3):732-738. doi: 10.1016/j.bbrc.2019.10.167. Epub 2019 Nov 7.
• [29] Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1.Mol Genet Genomic Med. 2020 Jan;8(1):e1023. doi: 10.1002/mgg3.1023. Epub 2019 Nov 27.
• [30] Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene.Endocr J. 2018 Feb 26;65(2):227-238. doi: 10.1507/endocrj.EJ17-0287. Epub 2017 Dec 2.
• [31] Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies.J Hum Genet. 2014 Jan;59(1):16-23. doi: 10.1038/jhg.2013.107. Epub 2013 Oct 24.
• [32] Transgenic Mice Overexpressing SREBP-1a in Male ob/ob Mice Exhibit Lipodystrophy and Exacerbate Insulin Resistance.Endocrinology. 2018 Jun 1;159(6):2308-2323. doi: 10.1210/en.2017-03179.
• [33] Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet. 2006 Aug;79(2):383-9. doi: 10.1086/505885. Epub 2006 Jun 5.
• [34] The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion.Sci Rep. 2017 Dec 14;7(1):17593. doi: 10.1038/s41598-017-17746-8.
• [35] Clinical review#: Lipodystrophies: genetic and acquired body fat disorders.J Clin Endocrinol Metab. 2011 Nov;96(11):3313-25. doi: 10.1210/jc.2011-1159. Epub 2011 Aug 24.
• [36] Adipocyte-specific disruption of mouse Cnot3 causes lipodystrophy.FEBS Lett. 2017 Jan;591(2):358-368. doi: 10.1002/1873-3468.12550. Epub 2017 Jan 12.
• [37] Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss.AIDS Res Hum Retroviruses. 2015 Aug;31(8):792-6. doi: 10.1089/AID.2014.0266. Epub 2015 Jun 15.
• [38] Effect of pathogenic mis-sense mutations in lamin A on its interaction with emerin in vivo.J Cell Sci. 2003 Jul 15;116(Pt 14):3027-35. doi: 10.1242/jcs.00599. Epub 2003 Jun 3.
• [39] Lipoatrophy and metabolic disturbance in mice with adipose-specific deletion of kindlin-2.JCI Insight. 2019 Jul 11;4(13):e128405. doi: 10.1172/jci.insight.128405. eCollection 2019 Jul 11.
• [40] A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. Dis Model Mech. 2017 Feb 1;10(2):105-118. doi: 10.1242/dmm.026476. Epub 2016 Dec 15.
• [41] The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes.J Intern Med. 2016 Jul;280(1):24-38. doi: 10.1111/joim.12444. Epub 2016 Mar 30.
• [42] Inherited lipodystrophies and hypertriglyceridemia.Curr Opin Lipidol. 2009 Aug;20(4):300-8. doi: 10.1097/MOL.0b013e32832d4a33.
• [43] Evaluation of Lipin 2 as a candidate gene for autosomal dominant 1 high-grade myopia.Gene. 2005 Jun 6;352:10-9. doi: 10.1016/j.gene.2005.02.019.
• [44] Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns.J Biol Chem. 2007 Feb 9;282(6):3450-7. doi: 10.1074/jbc.M610745200. Epub 2006 Dec 7.
• [45] Metformin paradoxically worsens insulin resistance in SHORT syndrome.Diabetol Metab Syndr. 2019 Oct 1;11:81. doi: 10.1186/s13098-019-0477-z. eCollection 2019.
• [46] Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation.Hum Mol Genet. 2016 Dec 1;25(23):5111-5125. doi: 10.1093/hmg/ddw315.
• [47] Disease-linked mutations in the phosphatidylcholine regulatory enzyme CCT impair enzymatic activity and fold stability.J Biol Chem. 2019 Feb 1;294(5):1490-1501. doi: 10.1074/jbc.RA118.006457. Epub 2018 Dec 17.
• [48] Ebf1-dependent control of the osteoblast and adipocyte lineages.Bone. 2009 Apr;44(4):537-46. doi: 10.1016/j.bone.2008.11.021. Epub 2008 Dec 16.