TMC3

Chr 15

transmembrane channel like 3

NCBI Gene: 342125 ENSG00000188869 UniProt: Q7Z5M5 OMIM: 617196

TMC3 encodes a predicted mechanosensitive ion channel component located in the plasma membrane that facilitates ion transport across cell membranes. The gene is not highly constrained against loss-of-function variants (pLI near 0, LOEUF >1), and no established human disease associations have been reported in the provided data. The molecular function and clinical significance of this gene remain to be fully characterized.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable mechanosensitive monoatomic ion channel activity. Predicted to be involved in monoatomic ion transmembrane transport. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.03

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.03LOEUF

pLI 0.000

Z-score 1.35

OE 0.79 (0.61–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.51Z-score

OE missense 0.94 (0.88–1.01)

582 obs / 618.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.61–1.03)

0≤0.351.4

Missense OE?0.94 (0.88–1.01)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 39 / 49.2Missense obs/exp: 582 / 618.0Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in TMC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 43

1,390 rare PASS variants

Rare truncating (LoF)

1 in 410

253 rare PASS variants

Rare synonymous (reference)

1 in 70

528 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMC3. 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 48	1 in 410
South Asian	~43k	1 in 28	1 in 290
Remaining (unassigned)	~30k	1 in 37	1 in 340
European (Finnish)	~27k	1 in 160	1 in 2,600
Admixed American	~22k	1 in 34	1 in 450
African / African American	~21k	1 in 31	1 in 230
East Asian	~20k	1 in 45	1 in 420
Ashkenazi Jewish	~13k	1 in 110	1 in 1,300
Middle Eastern	~2,884	1 in 34	1 in 530

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 22 coding exons well covered in gnomAD exomes; exons 9, 11, 15 marginal. Genomes: all 22.? see exons ↓