GPR15

Chr 3

G protein-coupled receptor 15

Also known as: BOB

NCBI Gene: 2838 ENSG00000154165 UniProt: P49685 OMIM: 601166

This protein functions as a G protein-coupled receptor that regulates immune homeostasis by controlling migration of regulatory T-cells to the large intestine and skin through chemokine signaling. Mutations cause autosomal recessive severe combined immunodeficiency with absence of peripheral T and NK cells and oral candidiasis. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a G protein-coupled receptor that acts as a chemokine receptor for human immunodeficiency virus type 1 and 2. The encoded protein localizes to the cell membrane. [provided by RefSeq, Nov 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.71

Clinical Summary— GPR15

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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

51 VUS of 57 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?

1.71LOEUF

pLI 0.000

Z-score -0.05

OE 1.02 (0.61–1.71)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.04Z-score

OE missense 1.01 (0.90–1.14)

197 obs / 195.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.02 (0.61–1.71)

0≤0.351.4

Missense OE?1.01 (0.90–1.14)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 9 / 8.8Missense obs/exp: 197 / 195.3Syn Z: -0.11

This gene — mechanism propensity

0.6744th %ile

GOF

0.6931th %ile

LOF

0.3162th %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

57 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

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	51	0	51
Likely Benign	3	1	4
Benign	1	1	2
Total	55	2	57

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap GPR15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →