TPRA1

Chr 3

transmembrane protein adipocyte associated 1

Also known as: GPR175, TMEM227, TPRA40

NCBI Gene: 131601 ENSG00000163870 UniProt: Q86W33 OMIM: 608336

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within embryonic cleavage and negative regulation of mitotic cell cycle phase transition. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.71

Clinical Summary— TPRA1

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

21 total variants — no pathogenic classifications of 21 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?

0.71LOEUF

pLI 0.015

Z-score 2.44

OE 0.36 (0.20–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.52Z-score

OE missense 0.90 (0.80–1.01)

201 obs / 222.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.20–0.71)

0≤0.351.4

Missense OE?0.90 (0.80–1.01)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 6 / 16.8Missense obs/exp: 201 / 222.7Syn Z: -0.83

This gene — mechanism propensity

0.74top 25%

GOF

0.76top 25%

LOF

0.3067th %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

21 submitted variants in ClinVar

ClinVar

Classification Summary

Benign2

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	0
Likely Pathogenic	—	—	—	—	0
VUS	—	—	—	—	0
Likely Benign	—	—	—	—	0
Benign	—	—	—	—	2
Total	—				2

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap TPRA1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →