GPR15

Chr 3

G protein-coupled receptor 15

Also known as: BOB

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.71
Clinical SummaryGPR15
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.71LOEUF
pLI 0.000
Z-score -0.05
OE 1.02 (0.611.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.04Z-score
OE missense 1.01 (0.901.14)
197 obs / 195.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.02 (0.611.71)
00.351.4
Missense OE1.01 (0.901.14)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 9 / 8.8Missense obs/exp: 197 / 195.3Syn Z: -0.11
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPR15 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗