Congenital generalized lipodystrophy type 4

Summary

Congenital generalized lipodystrophy type 4 (MONDO:0013225) is a disease caused by CAVIN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CAVIN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 84

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital generalized lipodystrophy type 4
Mondo ID	MONDO:0013225
MeSH	C567642
OMIM	613327
Orphanet	228429
DOID	DOID:0111138
UMLS	C2750069
MedGen	412871
GARD	0010937
Is cancer (heuristic)	no

Also known as: BSCL4 · CAVIN1 congenital generalised lipodystrophy (disease) · CAVIN1 congenital generalized lipodystrophy (disease) · CGL4 · congenital generalised lipodystrophy (disease) caused by mutation in CAVIN1 · congenital generalized lipodystrophy (disease) caused by mutation in CAVIN1 · GCL4 · lipodystrophy, congenital generalized, type 4

Data availability: 84 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 4

Related subtypes (4): congenital generalized lipodystrophy type 2, congenital generalized lipodystrophy type 1, congenital generalized lipodystrophy type 3, 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

84 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 12 benign, 12 likely benign, 9 conflicting classifications of pathogenicity, 8 pathogenic, 3 likely pathogenic, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2506963	NM_012232.6(CAVIN1):c.259C>T (p.Gln87Ter)	CAVIN1	Pathogenic	no assertion criteria provided
30327	NM_012232.6(CAVIN1):c.135del (p.Lys45fs)	CAVIN1	Pathogenic	no assertion criteria provided
30328	NM_012232.6(CAVIN1):c.478_481dup (p.Lys161fs)	CAVIN1	Pathogenic	no assertion criteria provided
30329	NM_012232.6(CAVIN1):c.518_521del (p.Lys173fs)	CAVIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30330	NM_012232.6(CAVIN1):c.471+1G>T	CAVIN1	Pathogenic	no assertion criteria provided
6601	NM_012232.6(CAVIN1):c.696dup (p.Lys233fs)	CAVIN1	Pathogenic	criteria provided, single submitter
6602	NM_012232.6(CAVIN1):c.526del (p.Glu176fs)	CAVIN1	Pathogenic	no assertion criteria provided
6603	NM_012232.6(CAVIN1):c.160del (p.Val54fs)	CAVIN1	Pathogenic	no assertion criteria provided
6604	NM_012232.6(CAVIN1):c.362dup (p.Lys122fs)	CAVIN1	Pathogenic	no assertion criteria provided
3236450	NM_012232.6(CAVIN1):c.512C>A (p.Ser171Ter)	CAVIN1	Likely pathogenic	criteria provided, single submitter
3764538	NM_012232.6(CAVIN1):c.1061_1091del (p.Glu354fs)	CAVIN1	Likely pathogenic	criteria provided, single submitter
982092	NM_012232.6(CAVIN1):c.550G>T (p.Glu184Ter)	CAVIN1	Likely pathogenic	criteria provided, single submitter
193359	NM_012232.6(CAVIN1):c.168C>A (p.Ser56Arg)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193361	NM_012232.6(CAVIN1):c.356T>A (p.Val119Asp)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195287	NM_012232.6(CAVIN1):c.*10G>A	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211974	NM_012232.6(CAVIN1):c.923A>G (p.Tyr308Cys)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323279	NM_012232.6(CAVIN1):c.462G>C (p.Met154Ile)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
436447	NM_012232.6(CAVIN1):c.540G>A (p.Glu180=)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
549548	NM_012232.6(CAVIN1):c.65C>T (p.Pro22Leu)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889147	NM_012232.6(CAVIN1):c.468C>T (p.Tyr156=)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889148	NM_012232.6(CAVIN1):c.232C>A (p.Arg78=)	CAVIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435295	NM_012232.6(CAVIN1):c.28G>C (p.Glu10Gln)	CAVIN1	Uncertain significance	criteria provided, single submitter
2435296	NM_012232.6(CAVIN1):c.62C>T (p.Ala21Val)	CAVIN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435297	NM_012232.6(CAVIN1):c.256G>A (p.Val86Met)	CAVIN1	Uncertain significance	criteria provided, single submitter
2435298	NM_012232.6(CAVIN1):c.743C>G (p.Thr248Ser)	CAVIN1	Uncertain significance	criteria provided, single submitter
2435299	NM_012232.6(CAVIN1):c.905C>T (p.Thr302Met)	CAVIN1	Uncertain significance	criteria provided, single submitter
2439771	NM_012232.6(CAVIN1):c.847C>T (p.Pro283Ser)	CAVIN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439772	NM_012232.6(CAVIN1):c.917T>C (p.Val306Ala)	CAVIN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
323255	NM_012232.6(CAVIN1):c.*1990A>C	CAVIN1	Uncertain significance	criteria provided, single submitter
323262	NM_012232.6(CAVIN1):c.*1479G>A	CAVIN1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
CAVIN1	Strong	Autosomal recessive	congenital generalized lipodystrophy type 4	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CAVIN1	Orphanet:228429	Congenital generalized lipodystrophy type 4

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
CAVIN1	HGNC:9688	ENSG00000177469	Q6NZI2	Caveolae-associated protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAVIN1	Caveolae-associated protein 1	Plays an important role in caveolae formation and organization.

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)
CAVIN1	Other/Unknown	no		Cavin_fam

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
popliteal artery	1
right coronary artery	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAVIN1	281	ubiquitous	marker	right coronary artery, tendon of biceps brachii, popliteal artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAVIN1	2,304

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAVIN1	Q6NZI2	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
RNA Polymerase I Transcription Termination	1	326.3×	0.017	CAVIN1
RNA Polymerase I Transcription	1	285.5×	0.017	CAVIN1
RHOB GTPase cycle	1	154.3×	0.017	CAVIN1
RHOC GTPase cycle	1	146.4×	0.017	CAVIN1
RHOA GTPase cycle	1	74.6×	0.027	CAVIN1
RHO GTPase cycle	1	60.1×	0.028	CAVIN1
Signaling by Rho GTPases	1	34.2×	0.037	CAVIN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.037	CAVIN1
Gene expression (Transcription)	1	17.8×	0.062	CAVIN1
Signal Transduction	1	10.2×	0.098	CAVIN1

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
termination of RNA polymerase I transcription	1	5617.3×	9e-04	CAVIN1
transcription initiation at RNA polymerase I promoter	1	1872.4×	0.001	CAVIN1
rRNA transcription	1	991.3×	0.002	CAVIN1
positive regulation of cell motility	1	766.0×	0.002	CAVIN1
protein secretion	1	263.3×	0.004	CAVIN1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CAVIN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CAVIN1

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)
CAVIN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.