TRPC1

Chr 3

transient receptor potential cation channel subfamily C member 1

Also known as: HTRP-1, TRP1

NCBI Gene: 7220 ENSG00000144935 UniProt: P48995 OMIM: 602343

The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — TRPC1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.013

Z-score 4.10

OE 0.29 (0.18–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.05Z-score

OE missense 0.58 (0.52–0.65)

242 obs / 417.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.29 (0.18–0.47)

0≤0.351.4

Missense OE?0.58 (0.52–0.65)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 38.5Missense obs/exp: 242 / 417.1Syn Z: 0.90

Background carrier burden — how many people carry a rare variant somewhere in TRPC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

756 rare PASS variants

Rare truncating (LoF)

1 in 1,800

108 rare PASS variants

Rare synonymous (reference)

1 in 160

306 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRPC1. 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 160	1 in 2,500
South Asian	~43k	1 in 88	1 in 890
Remaining (unassigned)	~30k	1 in 110	1 in 2,000
European (Finnish)	~27k	1 in 630	1 in 2,200
Admixed American	~22k	1 in 180	1 in 1,000
African / African American	~21k	1 in 140	1 in 1,100
East Asian	~20k	1 in 120	1 in 650
Ashkenazi Jewish	~13k	1 in 360	1 in 660
Middle Eastern	~2,884	1 in 86	≈ 1 in 2,900

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): 11 of 13 coding exons well covered in gnomAD exomes; exons 3, 10 marginal. Genomes: all 13.? see exons ↓