CAV1

Chr 7ARAD

caveolin 1

NCBI Gene: 857 ENSG00000105974 UniProt: Q03135

May act as a scaffolding protein within caveolar membranes (PubMed:11751885). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae (PubMed:19262564). Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway (By similarity). Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation (PubMed:25893292). Binds 20(S)-hydroxycholesterol (20(S)-OHC) (By similarity)

Primary Disease Associations & Inheritance

Lipodystrophy, congenital generalized, type 3MIM #612526

Lipodystrophy, familial partial, type 7MIM #606721

Pulmonary hypertension, primary, 3MIM #615343

227

ClinVar variants

Pathogenic / LP

0.01

pLI score

Active trials

Clinical Summary— CAV1

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

18 Pathogenic / Likely Pathogenic· 78 VUS of 227 total submissions

💊

Clinical Trials

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.67Z-score

OE missense 0.82 (0.69–0.98)

86 obs / 105.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.28–1.31)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.69–0.98)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	11	0	13
Likely Pathogenic	3	0	2	0	5
VUS	1	65	12	0	78
Likely Benign	0	7	23	52	82
Benign	0	0	12	0	12
Conflicting	—				6
Total	6	72	60	52	196

CAV1

Primary Disease Associations & Inheritance

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

DECIPHER · Gene2Phenotype

Gene2Phenotype Curations

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources