TMPRSS4

Chr 11

transmembrane serine protease 4

Also known as: CAP2, CAPH2, MT-SP2, TMPRSS3

NCBI Gene: 56649 ENSG00000137648 UniProt: Q9NRS4 OMIM: 606565

This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.01

LOEUF

Mechanism· predicted

📖

GeneReview available — TMPRSS4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.000

Z-score 1.51

OE 0.67 (0.45–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.94 (0.84–1.04)

242 obs / 257.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.45–1.01)

0≤0.351.4

Missense OE?0.94 (0.84–1.04)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 16 / 24.0Missense obs/exp: 242 / 257.7Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in TMPRSS4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

579 rare PASS variants

Rare truncating (LoF)

1 in 1,600

92 rare PASS variants

Rare synonymous (reference)

1 in 210

218 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMPRSS4. 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 86	1 in 2,400
South Asian	~43k	1 in 83	1 in 1,000
Remaining (unassigned)	~30k	1 in 84	1 in 1,400
European (Finnish)	~27k	1 in 440	1 in 4,400
Admixed American	~22k	1 in 84	1 in 2,000
African / African American	~21k	1 in 82	1 in 1,500
East Asian	~20k	1 in 130	1 in 2,000
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 64	≈ 1 in 720

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 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓