GPR88

Chr 1

G protein-coupled receptor 88

Also known as: COCPMR, STRG

NCBI Gene: 54112 ENSG00000181656 UniProt: Q9GZN0

This protein is an orphan G protein-coupled receptor expressed almost exclusively in the striatum that couples with G(i) protein complexes and modulates dopamine and adrenergic receptor signaling pathways involved in motor function, spatial learning, and emotional processing. Mutations cause autosomal recessive childhood-onset chorea with psychomotor retardation, speech delay, and learning difficulties. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.528), suggesting intolerance to complete protein loss.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a G protein-coupled receptor found almost exclusively in the striatum, a brain structure that controls motor function and cognition. Defects in this gene have been associated with chorea, speech delay, and learning difficulties, as well as some neuropsychiatric disorders. [provided by RefSeq, Mar 2017]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.53

Clinical Summary— GPR88

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 61 VUS of 104 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.755

Z-score 2.47

OE 0.11 (0.04–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.03Z-score

OE missense 0.36 (0.30–0.45)

65 obs / 179.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.53)

0≤0.351.4

Missense OE?0.36 (0.30–0.45)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 9.0Missense obs/exp: 65 / 179.1Syn Z: -0.37

This gene — mechanism propensity

0.4983th %ile

GOF

0.80top 10%

LOF

0.56top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS61

Likely Benign38

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	60	1	0	61
Likely Benign	0	0	0	38	38
Benign	0	1	0	2	3
Total	1	61	1	40	103

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap GPR88 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →