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.

not_specified (19 variants)
not_provided (11 variants)
TMPRSS2-related_disorder (3 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (2 variants)
Prostate_cancer (1 variants)

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. These statistics are base on transcript: NM_000005656.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	5 clinvar	8
missense			14 clinvar	6 clinvar	3 clinvar	23
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	15	9	8

Loading clinvar variants...

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
ghis

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