TMPRSS11D

Chr 4

transmembrane serine protease 11D

Also known as: ASP, HAT

NCBI Gene: 9407 ENSG00000153802 UniProt: O60235 OMIM: 605369

The protein encoded by this gene is a trypsin-like serine protease that is released from submucosal serous glands and cleaves viral envelope glycoproteins to facilitate viral entry into host cells, while also playing a role in mucosal host defense. This gene is not well-constrained against loss-of-function variants and is not currently associated with established Mendelian disease in pediatric patients.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a trypsin-like serine protease released from the submucosal serous glands onto mucous membrane. It is a type II integral membrane protein and has 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region has little similarity to other known proteins. This protein may play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.92

Clinical Summary— TMPRSS11D

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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

47 VUS of 56 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?

0.92LOEUF

pLI 0.000

Z-score 1.84

OE 0.55 (0.35–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.48Z-score

OE missense 0.91 (0.81–1.02)

198 obs / 218.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.35–0.92)

0≤0.351.4

Missense OE?0.91 (0.81–1.02)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 11 / 19.9Missense obs/exp: 198 / 218.1Syn Z: -0.56

This gene — mechanism propensity

0.76top 25%

GOF

0.6053th %ile

LOF

0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	47	47
Likely Benign	5	5
Benign	0	0
Total	52	52

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap TMPRSS11D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →