TRPC6

Chr 11AD

transient receptor potential cation channel subfamily C member 6

Also known as: FSGS2, TRP6

NCBI Gene: 7225 ENSG00000137672 UniProt: Q9Y210 OMIM: 603652

The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glomerulosclerosis, focal segmental, 2MIM #603965

UniProtFocal segmental glomerulosclerosis 2

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Glomerulosclerosis, focal segmental; no ClinGen or GenCC tier

Active trials

144

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.31

OE 0.44 (0.30–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.12Z-score

OE missense 0.73 (0.67–0.80)

361 obs / 493.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.44 (0.30–0.65)

0≤0.351.4

Missense OE?0.73 (0.67–0.80)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 18 / 40.8Missense obs/exp: 361 / 493.7Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in TRPC6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

1,077 rare PASS variants

Rare truncating (LoF)

1 in 1,200

159 rare PASS variants

Rare synonymous (reference)

1 in 100

427 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRPC6. 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 93	1 in 1,300
South Asian	~43k	1 in 56	1 in 1,200
Remaining (unassigned)	~30k	1 in 83	1 in 790
European (Finnish)	~27k	1 in 340	1 in 5,300
Admixed American	~22k	1 in 64	1 in 850
African / African American	~21k	1 in 71	1 in 1,200
East Asian	~20k	1 in 100	1 in 1,200
Ashkenazi Jewish	~13k	1 in 680	≈ 1 in 3,800
Middle Eastern	~2,884	1 in 67	≈ 1 in 960

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 10 poorly covered. Genomes: all 13.? see exons ↓