MRGPRF

Chr 11

MAS related GPR family member F

Also known as: GPR140, GPR168, MRGF, RTA

NCBI Gene: 116535 ENSG00000172935 UniProt: Q96AM1 OMIM: 607233

The MRGPRF protein is a G protein-coupled receptor that may bind neuropeptides and regulate pain sensation and nociceptor function. Mutations cause autosomal recessive congenital insensitivity to pain, which presents in infancy with absence of pain perception leading to self-injury and complications. The gene shows low constraint to loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.024

Z-score 1.64

OE 0.42 (0.21–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.65Z-score

OE missense 0.88 (0.78–0.99)

187 obs / 213.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.21–0.97)

0≤0.351.4

Missense OE?0.88 (0.78–0.99)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 9.4Missense obs/exp: 187 / 213.6Syn Z: 0.33

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 81

665 rare PASS variants

Rare truncating (LoF)

1 in 1,400

83 rare PASS variants

Rare synonymous (reference)

1 in 98

312 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRGPRF. 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 120	1 in 1,500
South Asian	~43k	1 in 68	1 in 960
Remaining (unassigned)	~30k	1 in 71	1 in 1,700
European (Finnish)	~27k	1 in 330	1 in 1,200
Admixed American	~22k	1 in 61	1 in 1,000
African / African American	~21k	1 in 79	1 in 370
East Asian	~20k	1 in 98	1 in 870
Ashkenazi Jewish	~13k	1 in 620	≈ 1 in 2,700
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,000

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓