TMPRSS11D

Chr 4

transmembrane serine protease 11D

Also known as: ASP, HAT

NCBI Gene: 9407ENSG00000153802UniProt: O60235OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.92
Clinical Summary— TMPRSS11D
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 57 VUS of 85 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 OE0.55 (0.35–0.92)
0≤0.351.4
Missense OE0.91 (0.81–1.02)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 11 / 19.9Missense obs/exp: 198 / 218.1Syn Z: -0.56
DN
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

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS57
Likely Benign5
17
Pathogenic
2
Likely Pathogenic
57
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
2
0
2
VUS
0
47
10
0
57
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total05229081

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

View in ClinVar →

Protein Context — Lollipop Plot

TMPRSS11D · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Detection of SARS-CoV-2 binding receptors and miscellaneous targets as well as mucosal surface area of the human lacrimal drainage system.
Rau AL et al.·Ocul Surf
2024
Identification of p-aminobenzylamine derivatives as dual non-covalent inhibitors of the transmembrane host proteases TMPRSS2 and HAT proteases with anti-viral potential
Carvaillo H et al.·RSC Med Chem
2025
Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19 related gene for global cognitive function
Acharya V et al.·Alzheimers Dement
2023
The clinically used serine protease inhibitor nafamostat reduces influenza virus replication and cytokine production in human airway epithelial cells and viral replication in mice.
Yamaya M et al.·J Med Virol
2021
SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition
Erickson R et al.·Nat Commun
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients