GPR183

Chr 13

G protein-coupled receptor 183

Also known as: EBI2, hEBI2

NCBI Gene: 1880 ENSG00000169508 UniProt: P32249 OMIM: 605741

GPR183 encodes a G-protein coupled receptor that binds oxysterols and mediates chemotactic positioning of immune cells including B-cells, T-cells, dendritic cells, and astrocytes during immune responses. The gene shows low constraint to loss-of-function variants, and no established human disease associations have been reported despite its role in immune cell positioning and astrocyte migration. Currently, no inherited disorders linked to GPR183 mutations are recognized in clinical practice.

OMIM ResearchSummary from RefSeq, UniProt

This gene was identified by the up-regulation of its expression upon Epstein-Barr virus infection of primary B lymphocytes. This gene is predicted to encode a G protein-coupled receptor that is most closely related to the thrombin receptor. Expression of this gene was detected in B-lymphocyte cell lines and lymphoid tissues but not in T-lymphocyte cell lines or peripheral blood T lymphocytes. The function of this gene is unknown. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.017

Z-score 1.46

OE 0.46 (0.23–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.27Z-score

OE missense 0.75 (0.66–0.86)

153 obs / 204.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.23–1.06)

0≤0.351.4

Missense OE?0.75 (0.66–0.86)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 4 / 8.6Missense obs/exp: 153 / 204.2Syn Z: -1.23

Background carrier burden — how many people carry a rare variant somewhere in GPR183?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

384 rare PASS variants

Rare truncating (LoF)

1 in 13,000

23 rare PASS variants

Rare synonymous (reference)

1 in 250

173 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR183. 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 320	1 in 20,000
South Asian	~43k	1 in 130	1 in 8,500
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 30,000
European (Finnish)	~27k	1 in 460	≈ 1 in 13,000
Admixed American	~22k	1 in 250	1 in 2,700
African / African American	~21k	1 in 180	≈ 1 in 9,300
East Asian	~20k	1 in 350	none seen
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 83	none seen

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 ↓