TMPRSS5

Chr 11

transmembrane serine protease 5

NCBI Gene: 80975 ENSG00000166682 UniProt: Q9H3S3 OMIM: 606751

May play a role in hearing

OMIM Research

May play a role in hearing

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.37

OE 0.70 (0.48–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.92Z-score

OE missense 0.84 (0.75–0.94)

212 obs / 253.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.48–1.05)

0≤0.351.4

Missense OE?0.84 (0.75–0.94)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 17 / 24.3Missense obs/exp: 212 / 253.3Syn Z: 0.62

Background carrier burden — how many people carry a rare variant somewhere in TMPRSS5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 65

664 rare PASS variants

Rare truncating (LoF)

1 in 300

131 rare PASS variants

Rare synonymous (reference)

1 in 140

255 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TMPRSS5; this gene does not show strong loss-of-function constraint by this measure. 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 120	1 in 900
South Asian	~43k	1 in 76	1 in 280
Remaining (unassigned)	~30k	1 in 48	1 in 380
European (Finnish)	~27k	1 in 240	1 in 1,100
Admixed American	~22k	1 in 79	1 in 650
African / African American	~21k	1 in 72	1 in 280
East Asian	~20k	1 in 68	1 in 750
Ashkenazi Jewish	~13k	1 in 300	1 in 1,300
Middle Eastern	~2,884	1 in 86	≈ 1 in 2,800

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): 13 of 13 coding exons well covered in gnomAD exomes. Genomes: 12 of 13 (exon 11 below).? see exons ↓