TMPRSS3

transmembrane serine protease 3, the group of Scavenger receptor cysteine rich domain containing|Type II transmembrane serine proteases

Basic information

Region (hg38): 21:42371886-42396091

Previous symbols: [ "DFNB10", "DFNB8" ]

Links

ENSG00000160183 ∙ NCBI:64699 ∙ OMIM:605511 ∙ HGNC:11877 ∙ Uniprot:P57727 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 8 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 8 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 10; Deafness, autosomal recessive 8	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	11137999; 11907649; 16021470; 23226338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMPRSS3 gene.

• not provided (276 variants)
• Autosomal recessive nonsyndromic hearing loss 8 (127 variants)
• not specified (72 variants)
• Inborn genetic diseases (17 variants)
• Rare genetic deafness (14 variants)
• Hearing impairment (13 variants)
• TMPRSS3-related condition (4 variants)
• Nonsyndromic Hearing Loss, Recessive (4 variants)
• Hearing loss, autosomal recessive (3 variants)
• Nonsyndromic genetic hearing loss (2 variants)
• Childhood onset hearing loss (1 variants)
• Waardenburg syndrome (1 variants)
• Ear malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMPRSS3 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			6	47	2	55
missense	5	28	69	6	3	111
nonsense	9		1			10
start loss	1					1
frameshift	10	2	1			13
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2		1		4
splice region	1	1	7	11	1	21
non coding			34	46	42	122
Total	26	32	111	100	47

Highest pathogenic variant AF is 0.0000460

Variants in TMPRSS3

This is a list of pathogenic ClinVar variants found in the TMPRSS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-42371947-T-C		Autosomal recessive nonsyndromic hearing loss 8	Conflicting classifications of pathogenicity (Apr 01, 2023)
21-42371957-A-G		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Apr 27, 2017)
21-42371980-C-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42371985-C-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372007-C-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372012-G-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372070-C-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372098-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372183-AC-A		Nonsyndromic Hearing Loss, Recessive	Likely benign (Jun 14, 2016)
21-42372186-C-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372189-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372222-C-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372223-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372269-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372270-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372285-C-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372286-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372333-G-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372351-G-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372353-G-A		Autosomal recessive nonsyndromic hearing loss 8	Likely benign (Jan 13, 2018)
21-42372355-T-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372360-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)
21-42372365-G-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372428-C-T		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 12, 2018)
21-42372475-G-A		Autosomal recessive nonsyndromic hearing loss 8	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMPRSS3	protein_coding	protein_coding	ENST00000291532	12	24957

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.07e-11	0.395	125558	0	190	125748	0.000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.565	284	258	1.10	0.0000163	2944
Missense in Polyphen		103	104	0.99042		1109
Synonymous	-2.12	141	112	1.25	0.00000844	899
Loss of Function	1.10	19	24.9	0.763	0.00000125	289

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000749	0.000749
Ashkenazi Jewish	0.000993	0.000993
East Asian	0.000544	0.000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00127	0.00127
Middle Eastern	0.000544	0.000544
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable serine protease that plays a role in hearing. Acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival (By similarity). Activates ENaC (in vitro). {ECO:0000250, ECO:0000269|PubMed:12393794}.
• Disease: DISEASE: Deafness, autosomal recessive, 8 (DFNB8) [MIM:601072]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:11424922, ECO:0000269|PubMed:11462234, ECO:0000269|PubMed:11907649, ECO:0000269|PubMed:12393794, ECO:0000269|PubMed:15447792, ECO:0000269|PubMed:16021470}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.154
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.53

Haploinsufficiency Scores

• pHI: 0.0555
• hipred: N
• hipred_score: 0.342
• ghis: 0.452

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.847

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmprss3
• Phenotype: cellular phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: proteolysis;cellular sodium ion homeostasis;receptor-mediated endocytosis;sensory perception of sound
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;neuronal cell body
• Molecular function: serine-type endopeptidase activity;scavenger receptor activity;sodium channel regulator activity