GPRC5D

Chr 12

G protein-coupled receptor class C group 5 member D

NCBI Gene: 55507 ENSG00000111291 UniProt: Q9NZD1 OMIM: 607437

This protein is a G-protein coupled receptor involved in hard keratin expression and development of hair and nails. The gene is not well-constrained against loss-of-function variants, and no established disease associations have been reported in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the G protein-coupled receptor family; however, the specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

167

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.001

Z-score 1.85

OE 0.48 (0.27–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.62Z-score

OE missense 0.87 (0.77–0.99)

168 obs / 192.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.27–0.90)

0≤0.351.4

Missense OE?0.87 (0.77–0.99)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 7 / 14.6Missense obs/exp: 168 / 192.3Syn Z: -0.93

Background carrier burden — how many people carry a rare variant somewhere in GPRC5D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

415 rare PASS variants

Rare truncating (LoF)

1 in 980

55 rare PASS variants

Rare synonymous (reference)

1 in 240

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPRC5D. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 3.? see exons ↓