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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.71

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in TPRA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

527 rare PASS variants

Rare truncating (LoF)

1 in 620

90 rare PASS variants

Rare synonymous (reference)

1 in 360

170 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TPRA1. 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 130	1 in 3,600
South Asian	~43k	1 in 110	1 in 3,100
Remaining (unassigned)	~30k	1 in 79	1 in 430
European (Finnish)	~27k	1 in 280	≈ 1 in 13,000
Admixed American	~22k	1 in 94	≈ 1 in 7,500
African / African American	~21k	1 in 74	1 in 890
East Asian	~20k	1 in 130	1 in 260
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 91	1 in 570

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): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓