CAV1

Chr 7ARAD

caveolin 1

Also known as: BSCL3, CGL3, LCCNS, MSTP085, PPH3, VIP21

NCBI Gene: 857 ENSG00000105974 UniProt: Q03135 OMIM: 601047

Caveolin-1 is a scaffolding protein that forms caveolae plasma membrane structures and regulates multiple signaling pathways including integrin-FYN coupling and Wnt signaling. Mutations cause congenital generalized lipodystrophy type 3, familial partial lipodystrophy type 7, and primary pulmonary hypertension type 3 with both autosomal recessive and autosomal dominant inheritance patterns. The gene shows tolerance to loss-of-function variants (pLI 0.008, LOEUF 1.31), reflecting the multiple disease mechanisms possible with different variant types.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. Caveolin 1 and caveolin 2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. Mutations in this gene have been associated with Berardinelli-Seip congenital lipodystrophy. Alternatively spliced transcripts encode alpha and beta isoforms of caveolin 1.[provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 1.313 OMIM phenotypes

Clinical Summary— CAV1

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Gene-Disease Validity (ClinGen)

amyotrophic lateral sclerosis · ADLimited

Limited evidence — not for standalone diagnostic reporting

4 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

12 unique Pathogenic / Likely Pathogenic· 77 VUS of 198 total submissions

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Clinical Trials

5 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CAV1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.008

Z-score 1.03

OE 0.58 (0.28–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.82 (0.69–0.98)

86 obs / 105.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.28–1.31)

0≤0.351.4

Missense OE?0.82 (0.69–0.98)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 4 / 6.9Missense obs/exp: 86 / 105.3Syn Z: 0.81

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateCAV1-related congenital generalized lipodystrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.79top 25%

GOF

0.83top 5%

LOF

0.2872th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNWe conclude that the P158PfsX22 frameshift introduces a gain of function that gives rise to a dominant negative form of CAV1, defining a new mechanism by which disease-associated mutations in CAV1 impair caveolae assembly.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 28904206 ↗

ClinVar Variant Classifications

198 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic3

VUS77

Likely Benign85

Benign14

Conflicting6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	0	0	0	9
Likely Pathogenic	3	0	0	0	3
VUS	2	67	8	0	77
Likely Benign	0	7	23	55	85
Benign	0	0	14	0	14
Conflicting	—				6
Total	14	74	45	55	194

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

26 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap CAV1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →