Congenital generalized lipodystrophy type 3

Summary

Congenital generalized lipodystrophy type 3 (MONDO:0012923) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital generalized lipodystrophy type 3
Mondo ID	MONDO:0012923
MeSH	C567282
OMIM	612526
Orphanet	696206
DOID	DOID:0111137
UMLS	C2675861
MedGen	436541
GARD	0013389
Is cancer (heuristic)	no

Also known as: BSCL3 · CAV1 congenital generalised lipodystrophy (disease) · CAV1 congenital generalized lipodystrophy (disease) · CGL3 · congenital generalised lipodystrophy (disease) caused by mutation in CAV1 · congenital generalized lipodystrophy (disease) caused by mutation in CAV1 · lipodystrophy, congenital generalized, type 3 · type 3 Berardinelli-Seip congenital lipodystrophy

Data availability: 35 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › lipodystrophy › hereditary lipodystrophy › congenital generalized lipodystrophy › congenital generalized lipodystrophy type 3

Related subtypes (4): congenital generalized lipodystrophy type 2, congenital generalized lipodystrophy type 1, congenital generalized lipodystrophy type 4, lipodystrophy, congenital generalized, type 5

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

35 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 4 pathogenic, 3 likely benign, 2 benign, 2 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
208669	NM_001753.5(CAV1):c.479_480del (p.Leu159_Phe160insTer)	CAV1	Pathogenic	criteria provided, single submitter
209106	NM_001753.5(CAV1):c.424C>T (p.Gln142Ter)	CAV1	Pathogenic	no assertion criteria provided
2443747	NM_001753.5(CAV1):c.237_238del (p.His79fs)	CAV1	Pathogenic	no assertion criteria provided
8467	NM_001753.5(CAV1):c.112G>T (p.Glu38Ter)	CAV1	Pathogenic	criteria provided, single submitter
2894539	NM_001753.5(CAV1):c.358G>A (p.Ala120Thr)	CAV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541324	NM_001753.5(CAV1):c.500T>C (p.Phe167Ser)	CAV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1469176	NM_001753.5(CAV1):c.302G>A (p.Arg101His)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1677803	NM_001753.5(CAV1):c.394C>G (p.Pro132Ala)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803889	NM_001753.5(CAV1):c.236A>G (p.His79Arg)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2663785	NM_001753.5(CAV1):c.284C>T (p.Thr95Met)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594247	NM_001753.5(CAV1):c.30+3A>G	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594248	NM_001753.5(CAV1):c.31-5T>A	CAV1	Uncertain significance	criteria provided, single submitter
3594249	NM_001753.5(CAV1):c.87C>A (p.Asn29Lys)	CAV1	Uncertain significance	criteria provided, single submitter
3594250	NM_001753.5(CAV1):c.96G>A (p.Met32Ile)	CAV1	Uncertain significance	criteria provided, single submitter
3594252	NM_001753.5(CAV1):c.247G>A (p.Gly83Ser)	CAV1	Uncertain significance	criteria provided, single submitter
3594253	NM_001753.5(CAV1):c.301C>T (p.Arg101Cys)	CAV1	Uncertain significance	criteria provided, single submitter
3594255	NM_001753.5(CAV1):c.323G>A (p.Gly108Asp)	CAV1	Uncertain significance	criteria provided, single submitter
3594256	NM_001753.5(CAV1):c.413T>C (p.Leu138Pro)	CAV1	Uncertain significance	criteria provided, single submitter
3594257	NM_001753.5(CAV1):c.436C>T (p.Arg146Cys)	CAV1	Uncertain significance	criteria provided, single submitter
3594258	NM_001753.5(CAV1):c.454G>A (p.Val152Ile)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594259	NM_001753.5(CAV1):c.460A>T (p.Thr154Ser)	CAV1	Uncertain significance	criteria provided, single submitter
3594260	NM_001753.5(CAV1):c.461C>T (p.Thr154Ile)	CAV1	Uncertain significance	criteria provided, single submitter
3594261	NM_001753.5(CAV1):c.487G>C (p.Val163Leu)	CAV1	Uncertain significance	criteria provided, single submitter
3594262	NM_001753.5(CAV1):c.511C>T (p.Arg171Cys)	CAV1	Uncertain significance	criteria provided, single submitter
650998	NM_001753.5(CAV1):c.512G>A (p.Arg171His)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
944210	NM_001753.5(CAV1):c.202T>G (p.Phe68Val)	CAV1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3263577	NM_001753.5(CAV1):c.172C>T (p.His58Tyr)	LOC129999169	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594251	NM_001753.5(CAV1):c.194A>G (p.Lys65Arg)	LOC129999169	Uncertain significance	criteria provided, single submitter
1569990	NM_001753.5(CAV1):c.437G>C (p.Arg146Pro)	CAV1	Likely benign	criteria provided, multiple submitters, no conflicts
1601262	NM_001753.5(CAV1):c.30+20C>T	CAV1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CAV1	Strong	Autosomal dominant	partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CAV1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
CAV1	Orphanet:220402	Limited cutaneous systemic sclerosis
CAV1	Orphanet:275777	Heritable pulmonary arterial hypertension
CAV1	Orphanet:696206	Congenital generalized lipodystrophy type 3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CAV1	HGNC:1527	ENSG00000105974	Q03135	Caveolin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAV1	Caveolin-1	May act as a scaffolding protein within caveolar membranes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CAV1	Other/Unknown	no		Caveolin, Caveolin_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower lobe of lung	1
parietal pleura	1
pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAV1	287	ubiquitous	marker	parietal pleura, lower lobe of lung, pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAV1	6,673

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAV1	Q03135	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Metabolism of nitric oxide: NOS3 activation and regulation	1	2284.0×	0.010	CAV1
NOSTRIN mediated eNOS trafficking	1	2284.0×	0.010	CAV1
eNOS activation	1	878.5×	0.010	CAV1
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	1	878.5×	0.010	CAV1
Thyroxine biosynthesis	1	815.7×	0.010	CAV1
Triglyceride metabolism	1	671.8×	0.010	CAV1
FOXO-mediated transcription of cell cycle genes	1	671.8×	0.010	CAV1
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	671.8×	0.010	CAV1
Triglyceride catabolism	1	475.8×	0.012	CAV1
Basigin interactions	1	439.2×	0.012	CAV1
VEGFR2 mediated vascular permeability	1	407.9×	0.012	CAV1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.012	CAV1
FOXO-mediated transcription	1	335.9×	0.012	CAV1
RHOH GTPase cycle	1	308.6×	0.012	CAV1
RND1 GTPase cycle	1	265.6×	0.012	CAV1
RHOF GTPase cycle	1	259.6×	0.012	CAV1
RND3 GTPase cycle	1	259.6×	0.012	CAV1
RND2 GTPase cycle	1	259.6×	0.012	CAV1
Signaling by VEGF	1	219.6×	0.013	CAV1
RHOD GTPase cycle	1	203.9×	0.013	CAV1
RHOJ GTPase cycle	1	200.3×	0.013	CAV1
RHOQ GTPase cycle	1	181.3×	0.014	CAV1
SARS-CoV-1-host interactions	1	175.7×	0.014	CAV1
Extra-nuclear estrogen signaling	1	170.4×	0.014	CAV1
RHOB GTPase cycle	1	154.3×	0.014	CAV1
RHOG GTPase cycle	1	148.3×	0.014	CAV1
RHOC GTPase cycle	1	146.4×	0.014	CAV1
SARS-CoV-1 Infection	1	142.8×	0.014	CAV1
VEGFA-VEGFR2 Pathway	1	139.3×	0.014	CAV1
ESR-mediated signaling	1	128.3×	0.014	CAV1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of the force of heart contraction by chemical signal	1	8426.0×	0.002	CAV1
intracellular nitric oxide homeostasis	1	5617.3×	0.002	CAV1
insulin receptor internalization	1	5617.3×	0.002	CAV1
regulation of membrane repolarization during action potential	1	5617.3×	0.002	CAV1
protein localization to basolateral plasma membrane	1	5617.3×	0.002	CAV1
protein localization to plasma membrane raft	1	4213.0×	0.002	CAV1
negative regulation of pinocytosis	1	4213.0×	0.002	CAV1
maintenance of protein location in cell	1	3370.4×	0.002	CAV1
cellular response to hyperoxia	1	3370.4×	0.002	CAV1
caveolin-mediated endocytosis	1	3370.4×	0.002	CAV1
regulation of entry of bacterium into host cell	1	3370.4×	0.002	CAV1
mammary gland involution	1	2808.7×	0.002	CAV1
positive regulation of gap junction assembly	1	2407.4×	0.002	CAV1
glandular epithelial cell differentiation	1	2106.5×	0.002	CAV1
caveola assembly	1	2106.5×	0.002	CAV1
regulation of ruffle assembly	1	2106.5×	0.002	CAV1
negative regulation of cytokine-mediated signaling pathway	1	1872.4×	0.002	CAV1
regulation of fatty acid metabolic process	1	1872.4×	0.002	CAV1
regulation of blood coagulation	1	1872.4×	0.002	CAV1
regulation of cardiac muscle cell action potential involved in regulation of contraction	1	1872.4×	0.002	CAV1
regulation of cell communication by electrical coupling involved in cardiac conduction	1	1872.4×	0.002	CAV1
receptor-mediated endocytosis of virus by host cell	1	1532.0×	0.002	CAV1
angiotensin-activated signaling pathway	1	1532.0×	0.002	CAV1
nitric oxide metabolic process	1	1404.3×	0.002	CAV1
cellular response to misfolded protein	1	1404.3×	0.002	CAV1
regulation of ventricular cardiac muscle cell action potential	1	1404.3×	0.002	CAV1
negative regulation of potassium ion transmembrane transport	1	1404.3×	0.002	CAV1
regulation of smooth muscle contraction	1	1203.7×	0.003	CAV1
positive regulation of calcium ion transport into cytosol	1	1203.7×	0.003	CAV1
negative regulation of epithelial cell differentiation	1	1203.7×	0.003	CAV1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CAV1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CAV1	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CAV1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CAV1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.