TMPRSS2

transmembrane serine protease 2, the group of Type II transmembrane serine proteases|Scavenger receptor cysteine rich domain containing

Basic information

Region (hg38): 21:41464300-41531116

Links

ENSG00000184012 ∙ ∙ OMIM:602060 ∙ HGNC:11876 ∙ Uniprot:O15393 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMPRSS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMPRSS2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					5	5
missense			12		4	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			1	1	2	4
Total	0	0	13	1	11

Variants in TMPRSS2

This is a list of pathogenic ClinVar variants found in the TMPRSS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-41466152-G-C		not specified	Uncertain significance (Nov 20, 2024)
21-41467734-C-T		TMPRSS2-related disorder	Likely benign (Apr 01, 2025)
21-41467772-C-T		not specified	Uncertain significance (Apr 18, 2023)
21-41467856-T-G		not specified	Uncertain significance (May 13, 2024)
21-41468466-A-T		not specified	Uncertain significance (May 17, 2023)
21-41468486-CTG-C		Prostate cancer	Uncertain significance (-)
21-41470696-G-A		TMPRSS2-related disorder	Likely benign (Jul 16, 2023)
21-41471908-C-T		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
21-41471962-G-A		not specified	Likely benign (Mar 06, 2025)
21-41471981-T-C		not specified	Likely benign (Dec 11, 2023)
21-41473377-C-A		not specified	Uncertain significance (Dec 14, 2022)
21-41473432-C-T			Benign (Mar 29, 2018)
21-41473446-C-T		not specified	Uncertain significance (Aug 23, 2021)
21-41473479-T-C		not specified	Uncertain significance (Sep 07, 2022)
21-41473493-C-A		not specified	Uncertain significance (Oct 18, 2021)
21-41479207-G-A			Benign (May 23, 2018)
21-41480507-C-T		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
21-41480508-G-A			Benign (Dec 31, 2019)
21-41480570-C-T		Associated with severe COVID-19 disease	Benign (Feb 26, 2021)
21-41494370-G-A			Benign (Dec 31, 2019)
21-41494405-G-A			Benign (Jan 01, 2024)
21-41494421-G-A		not specified	Uncertain significance (Aug 30, 2021)
21-41494461-A-C			Benign (Jul 27, 2018)
21-41494495-G-A			Benign (Apr 17, 2018)
21-41494500-C-T		not specified	Uncertain significance (Jan 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMPRSS2	protein_coding	protein_coding	ENST00000398585	14	66566

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.40e-10	0.880	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.399	303	323	0.938	0.0000197	3428
Missense in Polyphen		108	126.63	0.85288		1357
Synonymous	0.758	132	144	0.919	0.0000109	1013
Loss of Function	1.81	20	30.9	0.648	0.00000132	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000490	0.000489
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000462
European (Non-Finnish)	0.000300	0.000299
Middle Eastern	0.0000544	0.0000544
South Asian	0.000198	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease that proteolytically cleaves and activates the viral spike glycoproteins 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. Facilitates human SARS coronavirus (SARS-CoV) infection via two independent mechanisms, proteolytic cleavage of ACE2, which might promote viral uptake, and cleavage of coronavirus spike glycoprotein which activates the glycoprotein for cathepsin L- independent host cell entry. Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843}.
• Pathway: Influenza A - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Coregulation of Androgen receptor activity;Regulation of Androgen receptor activity (Consensus)

Recessive Scores

• pRec: 0.195

Intolerance Scores

• loftool: 0.166
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.75

Haploinsufficiency Scores

• pHI: 0.293
• hipred: Y
• hipred_score: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0651

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Tmprss2
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; immune system phenotype; respiratory system phenotype; neoplasm

Gene ontology

• Biological process: proteolysis;receptor-mediated endocytosis;protein autoprocessing;positive regulation of viral entry into host cell
• Cellular component: plasma membrane;integral component of plasma membrane;extracellular exosome
• Molecular function: serine-type endopeptidase activity;scavenger receptor activity;protein binding;serine-type peptidase activity