GPRC5A

Chr 12

G protein-coupled receptor class C group 5 member A

Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218)

0
Active trials
19
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.63
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryGPRC5A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.63LOEUF
pLI 0.000
Z-score 0.00
OE 1.00 (0.631.63)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.62Z-score
OE missense 1.12 (1.011.25)
233 obs / 207.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.00 (0.631.63)
00.351.4
Missense OE1.12 (1.011.25)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 11 / 11.0Missense obs/exp: 233 / 207.9Syn Z: -0.34
DN
0.6745th %ile
GOF
0.75top 25%
LOF
0.3260th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPRC5A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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