GPR180

Chr 13

G protein-coupled receptor 180

Also known as: ITR

NCBI Gene: 160897 ENSG00000152749 UniProt: Q86V85 OMIM: 607787

This gene encodes a G protein-coupled receptor expressed predominantly in vascular smooth muscle cells that regulates vascular remodeling. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay. The gene is not highly constrained against loss-of-function variation, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq

This gene encodes a protein that is a member of the G protein-coupled receptor superfamily. This protein is produced predominantly in vascular smooth muscle cells and may play an important role in the regulation of vascular remodeling. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.11

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.000

Z-score 1.18

OE 0.73 (0.49–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.76Z-score

OE missense 0.86 (0.76–0.96)

188 obs / 219.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.49–1.11)

0≤0.351.4

Missense OE?0.86 (0.76–0.96)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 16 / 22.0Missense obs/exp: 188 / 219.8Syn Z: 0.35

Background carrier burden — how many people carry a rare variant somewhere in GPR180?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

564 rare PASS variants

Rare truncating (LoF)

1 in 870

112 rare PASS variants

Rare synonymous (reference)

1 in 340

210 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR180. 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 160	1 in 1,000
South Asian	~43k	1 in 73	1 in 1,600
Remaining (unassigned)	~30k	1 in 97	1 in 690
European (Finnish)	~27k	1 in 230	1 in 1,100
Admixed American	~22k	1 in 110	1 in 660
African / African American	~21k	1 in 150	1 in 1,800
East Asian	~20k	1 in 120	1 in 1,200
Ashkenazi Jewish	~13k	1 in 350	1 in 1,200
Middle Eastern	~2,884	1 in 230	≈ 1 in 860

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): 7 of 9 coding exons well covered in gnomAD exomes; exons 1, 8 marginal. Genomes: all 9.? see exons ↓