GPR155

Chr 2

G protein-coupled receptor 155

Also known as: DEP.7, DEPDC3, LYCHOS, PGR22

NCBI Gene: 151556 ENSG00000163328 UniProt: Q7Z3F1 OMIM: 620855

Enables cholesterol binding activity. Involved in several processes, including cellular response to amino acid starvation; cellular response to cholesterol; and positive regulation of TORC1 signaling. Located in extracellular exosome. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.97

Clinical Summary— GPR155

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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

103 VUS of 126 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.69

OE 0.72 (0.54–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.61Z-score

OE missense 0.79 (0.72–0.86)

360 obs / 457.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.54–0.97)

0≤0.351.4

Missense OE?0.79 (0.72–0.86)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 30 / 41.8Missense obs/exp: 360 / 457.0Syn Z: 0.70

This gene — mechanism propensity

0.6259th %ile

GOF

0.6737th %ile

LOF

0.3355th %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

126 submitted variants in ClinVar

ClinVar

Classification Summary

VUS103

Likely Benign5

Benign4

103

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	0	0	0
VUS	103	0	103
Likely Benign	3	2	5
Benign	0	4	4
Total	106	6	112

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap GPR155 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →