TMPRSS11E

Chr 4

transmembrane serine protease 11E

Also known as: DESC1, TMPRSS11E2

NCBI Gene: 28983 ENSG00000087128 UniProt: Q9UL52 OMIM: 610399

The protein is a serine protease with gelatinolytic and caseinolytic activities that shows preference for arginine at the P1 position and is predicted to be active at the plasma membrane. Mutations cause autosomal recessive intellectual disability, with this gene being highly tolerant to loss-of-function variants in the general population. The condition primarily affects cognitive development and is inherited in an autosomal recessive pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be located in extracellular region and membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 1.89

OE 0.58 (0.38–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.31Z-score

OE missense 0.94 (0.84–1.05)

217 obs / 230.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.38–0.91)

0≤0.351.4

Missense OE?0.94 (0.84–1.05)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 14 / 24.0Missense obs/exp: 217 / 230.2Syn Z: -0.16

Background carrier burden — how many people carry a rare variant somewhere in TMPRSS11E?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

566 rare PASS variants

Rare truncating (LoF)

1 in 620

107 rare PASS variants

Rare synonymous (reference)

1 in 310

171 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TMPRSS11E; 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 190	1 in 660
South Asian	~43k	1 in 95	1 in 490
Remaining (unassigned)	~30k	1 in 140	1 in 330
European (Finnish)	~27k	1 in 740	none seen
Admixed American	~22k	1 in 100	1 in 320
African / African American	~21k	1 in 150	1 in 450
East Asian	~20k	1 in 150	1 in 1,300
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 83	≈ 1 in 940

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