TRPC4

Chr 13

transient receptor potential cation channel subfamily C member 4

Also known as: HTRP-4, HTRP4, TRP4

NCBI Gene: 7223 ENSG00000133107 UniProt: Q9UBN4

The protein forms a receptor-activated calcium-permeable cation channel that regulates endothelial permeability, vasodilation, and neurotransmitter release. Mutations cause generalized epilepsy with photosensitivity, with inheritance pattern not yet clearly established. The gene shows significant constraint against loss-of-function variants (LOEUF 0.373), suggesting that complete loss of protein function may be poorly tolerated.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

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

0.37

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.37LOEUF

pLI 0.482

Z-score 4.87

OE 0.22 (0.14–0.37)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.61Z-score

OE missense 0.68 (0.62–0.74)

353 obs / 520.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.14–0.37)

0≤0.351.4

Missense OE?0.68 (0.62–0.74)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 10 / 45.5Missense obs/exp: 353 / 520.7Syn Z: -0.83

Background carrier burden — how many people carry a rare variant somewhere in TRPC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

977 rare PASS variants

Rare truncating (LoF)

1 in 2,300

115 rare PASS variants

Rare synonymous (reference)

1 in 94

492 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRPC4. 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 150	1 in 2,800
South Asian	~43k	1 in 100	1 in 780
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 7,500
European (Finnish)	~27k	1 in 350	≈ 1 in 12,000
Admixed American	~22k	1 in 110	1 in 790
African / African American	~21k	1 in 82	1 in 1,200
East Asian	~20k	1 in 81	1 in 2,400
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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 ↓