RCVRN

Chr 17

recoverin

Also known as: RCV1

NCBI Gene: 5957 ENSG00000109047 UniProt: P35243 OMIM: 179618

Recoverin is a calcium sensor protein that regulates phototransduction in retinal photoreceptor cells by modulating rhodopsin phosphorylation and enhancing vision in dim light conditions. Mutations cause cone-rod dystrophy and retinal dystrophy with progressive vision loss. The gene shows very low constraint against loss-of-function variants and inheritance pattern is autosomal recessive.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the recoverin family of neuronal calcium sensors. The encoded protein contains three calcium-binding EF-hand domains and may prolong the termination of the phototransduction cascade in the retina by blocking the phosphorylation of photo-activated rhodopsin. Recoverin may be the antigen responsible for cancer-associated retinopathy. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.85

Clinical Summary— RCVRN

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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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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.000

Z-score -0.76

OE 1.27 (0.80–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.94 (0.80–1.09)

114 obs / 121.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.27 (0.80–1.85)

0≤0.351.4

Missense OE?0.94 (0.80–1.09)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 12 / 9.5Missense obs/exp: 114 / 121.9Syn Z: -0.12

This gene — mechanism propensity

0.73top 25%

GOF

0.72top 25%

LOF

0.2871th %ile

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

DNprediction above median

GOFprediction 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.