TMPRSS11D
protein-codingtransmembrane serine protease 11D, the group of Type II transmembrane serine proteases
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~63.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMPRSS11D variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004262.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 47 | 5 | 52 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 49 | 5 | 0 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004253.1 | 10 | MANE Select | |
| Ensembl | ENSP00000283916.6 | 10 | MANE Select | |
| Ensembl | ENSP00000421381.1 | 3 | Standard | |
| RefSeq | XP_016864340.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteolysis
- respiratory gaseous exchange
Molecular Function
- serine-type endopeptidase activity
- peptidase activity
Cellular Component
- extracellular region
- integral component of plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000283916
- Coding exons
- 10
- Length
- 63157
- Individuals with no LoFs
- 125688
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 56
- Defined
- 125744
- p
- 0.000223
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.484 | 198 | 218 | 0.908 | 0.0000109 | 2714 |
| Missense (PolyPhen) | 68 | 82.733 | 0.82192 | 1042 | ||
| Synonymous | -0.563 | 84 | 77.7 | 1.08 | 0.00000395 | 823 |
| Loss of Function | 1.84 | 11 | 19.9 | 0.553 | 9.35e-7 | 251 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00042 | 0.00041 | rare |
| South Asian | 0.000080 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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. Plays a role in the proteolytic processing of ACE2. Proteolytically cleaves and activates the human coronavirus 229E (HCoV-229E) spike glycoprotein which facilitate virus-cell membrane fusions; spike proteins are synthesized and maintained in precursor intermediate folding states and proteolysis permits the refolding and energy release required to create stable virus-cell linkages and membrane coalescence. Preferentially cleaves the C-terminal side of arginine residues at the P1 position of certain peptides, cleaving Boc-Phe-Ser-Arg-4-methylcoumaryl-7-amide most efficiently and having an optimum pH of 8.6 with this substrate. {ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:24227843}.;
Recessive Scores
- pRec
- 0.519
Intolerance Scores
- LoFtool
- 0.304
- RVIS EVS
- -0.74
- RVIS percentile EVS
- 13.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.108
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |