CAVIN2

Chr 2

caveolae associated protein 2

Also known as: PS-p68, SDPR, SDR, cavin-2

NCBI Gene: 8436 ENSG00000168497 UniProt: O95810 OMIM: 606728

The CAVIN2 protein regulates caveolar biogenesis and morphology by inducing membrane curvature within caveolae and recruiting polymerase I and transcript release factor to these membrane structures. Mutations cause lipodystrophy with muscular dystrophy through autosomal recessive inheritance. This gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a calcium-independent phospholipid-binding protein whose expression increases in serum-starved cells. This protein is a substrate for protein kinase C (PKC) phosphorylation and recruits polymerase I and transcript release factor (PTRF) to caveolae. Removal of this protein causes caveolae loss and its over-expression results in caveolae deformation and membrane tubulation.[provided by RefSeq, Sep 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.70

Clinical Summary— CAVIN2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

73 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.70LOEUF

pLI 0.000

Z-score -0.25

OE 1.08 (0.69–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.96 (0.86–1.06)

251 obs / 262.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.08 (0.69–1.70)

0≤0.351.4

Missense OE?0.96 (0.86–1.06)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 12 / 11.1Missense obs/exp: 251 / 262.2Syn Z: 0.67

This gene — mechanism propensity

0.6939th %ile

GOF

0.73top 25%

LOF

0.4136th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

VUS73

Likely Benign4

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	73	0	73
Likely Benign	2	2	4
Benign	0	2	2
Total	75	4	79

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap CAVIN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →