TMC7

Chr 16

transmembrane channel like 7

NCBI Gene: 79905 ENSG00000170537 UniProt: Q7Z402 OMIM: 617198

TMC7 encodes a protein that acts as an inhibitory modulator of PIEZO2 mechanosensitive channels in dorsal root ganglion neurons, regulating mechanical sensation. Mutations cause autosomal recessive epidermodysplasia verruciformis, susceptibility to type 2, which involves increased susceptibility to human papillomavirus infections and skin lesions. The gene shows tolerance to loss-of-function variation (LOEUF 0.825), suggesting the recessive inheritance pattern aligns with the constraint data.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable ion channel inhibitor activity and mechanosensitive monoatomic ion channel activity. Predicted to be involved in sensory perception of mechanical stimulus. Predicted to be located in plasma membrane. Predicted to be active in neuronal cell body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.82

Clinical Summary— TMC7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

111 VUS of 140 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.40

OE 0.57 (0.41–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.26Z-score

OE missense 0.83 (0.76–0.90)

342 obs / 414.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.41–0.82)

0≤0.351.4

Missense OE?0.83 (0.76–0.90)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 21 / 36.7Missense obs/exp: 342 / 414.0Syn Z: -0.34

This gene — mechanism propensity

0.75top 25%

GOF

0.75top 25%

LOF

0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

140 submitted variants in ClinVar

ClinVar

Classification Summary

VUS111

Likely Benign4

Benign2

111

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	111	0	0	111
Likely Benign	3	0	1	4
Benign	1	1	0	2
Total	115	1	1	117

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap TMC7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →