GPR31

Chr 6

G protein-coupled receptor 31

Also known as: 12-HETER, HETER, HETER1

NCBI Gene: 2853 ENSG00000120436 UniProt: O00270 OMIM: 602043

The GPR31 protein is a G protein-coupled receptor that binds 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-S-HETE), an arachidonic acid metabolite, and activates downstream signaling pathways including ERK1/2, MEK, and NF-kappa-B that promote cell growth and survival. This gene shows low constraint against loss-of-function variants (pLI = 0.02, LOEUF = 1.9), and no definitive Mendelian disease associations have been established in the provided data. The inheritance pattern for any potential disease associations remains undefined.

OMIM ResearchSummary from RefSeq, UniProt

Enables G protein-coupled receptor activity and arachidonate binding activity. Involved in G protein-coupled receptor signaling pathway and response to acidic pH. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.91

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.021

Z-score -0.24

OE 1.20 (0.41–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.29Z-score

OE missense 1.06 (0.94–1.19)

200 obs / 188.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.20 (0.41–1.91)

0≤0.351.4

Missense OE?1.06 (0.94–1.19)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 2 / 1.7Missense obs/exp: 200 / 188.7Syn Z: -1.25

Background carrier burden — how many people carry a rare variant somewhere in GPR31?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

429 rare PASS variants

Rare truncating (LoF)

1 in 860

44 rare PASS variants

Rare synonymous (reference)

1 in 300

220 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR31. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 1,100
South Asian	~43k	1 in 130	1 in 1,500
Remaining (unassigned)	~30k	1 in 69	1 in 420
European (Finnish)	~27k	1 in 190	1 in 4,500
Admixed American	~22k	1 in 130	1 in 1,600
African / African American	~21k	1 in 89	1 in 350
East Asian	~20k	1 in 91	1 in 830
Ashkenazi Jewish	~13k	1 in 350	none seen
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓