GPR153

Chr 1

G protein-coupled receptor 153

Also known as: PGR1

NCBI Gene: 387509 ENSG00000158292 UniProt: Q6NV75 OMIM: 614269

This gene encodes a G protein-coupled receptor that is expressed primarily in the central nervous system and functions as an orphan receptor. Mutations cause schizophrenia, autism, and other neuropsychiatric disorders with autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants, suggesting tolerance to such changes.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an integral membrane protein that belongs to the Class A rhodopsin superfamily of G protein coupled receptors. The encoded protein is expressed primarily in the central nervous system. A knockdown of the orthologous gene in rat is associated with a significant reduction in food intake and impaired decision making ability. Mutations in this gene are associated with schizophrenia, autism, and other neuropsychiatric disorders. The expression of this gene is activated by the glioma-associated oncogene homolog 1 transcription factor which, in turn, is activated by sonic hedgehog in normal and tumorigenic cells. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.29

Clinical Summary— GPR153

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 125 VUS of 149 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.76

OE 0.78 (0.49–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.89 (0.80–0.99)

240 obs / 271.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.49–1.29)

0≤0.351.4

Missense OE?0.89 (0.80–0.99)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 11 / 14.1Missense obs/exp: 240 / 271.0Syn Z: 0.13

This gene — mechanism propensity

0.6453th %ile

GOF

0.75top 25%

LOF

0.4726th %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

149 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS125

Likely Benign10

Benign3

Likely Pathogenic

125

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	125	0	125
Likely Benign	7	3	10
Benign	2	1	3
Total	135	4	139

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap GPR153 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →