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TMPRSS3 transmembrane serine protease 3 [ Homo sapiens (human) ]

Gene ID: 64699, updated on 5-Mar-2024

Summary

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Official Symbol
TMPRSS3provided by HGNC
Official Full Name
transmembrane serine protease 3provided by HGNC
Primary source
HGNC:HGNC:11877
See related
Ensembl:ENSG00000160183 MIM:605511; AllianceGenome:HGNC:11877
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DFNB8; DFNB10; ECHOS1; TADG12
Summary
This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a serine protease domain, a transmembrane domain, an LDL receptor-like domain, and a scavenger receptor cysteine-rich domain. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified by its association with both congenital and childhood onset autosomal recessive deafness. This gene is expressed in fetal cochlea and many other tissues, and is thought to be involved in the development and maintenance of the inner ear or the contents of the perilymph and endolymph. This gene was also identified as a tumor-associated gene that is overexpressed in ovarian tumors. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]
Expression
Biased expression in stomach (RPKM 9.6), gall bladder (RPKM 3.7) and 7 other tissues See more
Orthologs
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Genomic context

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Location:
21q22.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (42371890..42396052, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (40761358..40785622, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (43791999..43816161, complement)

Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372815 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:43781589-43782088 Neighboring gene trefoil factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13342 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr21:43787692-43788891 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:43789597-43790587 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:43792792-43793740 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:43796799-43797369 Neighboring gene trefoil factor 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:43808797-43809682 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18513 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr21:43814254-43815453 Neighboring gene ubiquitin associated and SH3 domain containing A Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr21:43834765-43835964 Neighboring gene RNA, U6 small nuclear 1149, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18516 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:43857898-43858585 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:43858586-43859272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13343 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18517 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:43883987-43884498 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18518 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr21:43887967-43889166 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18519 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18520 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18521 Neighboring gene radial spoke head component 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:43912470-43913669 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13344

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation. Chen YS, et al. J Med Genet, 2022 Dec. PMID 35961784, Free PMC Article
  2. Upregulation of the transmembrane protease serine 3 mRNA level in radioresistant colorectal cancer tissues. Wen JY, et al. Biomark Med, 2022 Jun. PMID 35543030
  3. [Mutational analysis and prenatal diagnosis of TMPRSS3 gene in two Chinese families affected with deafness]. Ren SM, et al. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2020 Apr 7. PMID 32306631
  4. Novel Mutations in the TMPRSS3 Gene may Contribute to Taiwanese Patients with Nonsyndromic Hearing Loss. Wong SH, et al. Int J Mol Sci, 2020 Mar 30. PMID 32235586, Free PMC Article
  5. TMPRSS3 regulates cell viability and apoptosis processes of HEI-OC1 cells via regulation of the circ-Slc4a2, miR-182 and Akt cascade. Zhang ZW, et al. J Gene Med, 2019 Oct. PMID 31408246

See all (65) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genotype-Phenotype Correlations in TMPRSS3 (DFNB10/DFNB8) with Emphasis on Natural History.
    Title: Genotype-Phenotype Correlations in TMPRSS3 (DFNB10/DFNB8) with Emphasis on Natural History.
  2. TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation.
    Title: TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation.
  3. Upregulation of the transmembrane protease serine 3 mRNA level in radioresistant colorectal cancer tissues.
    Title: Upregulation of the transmembrane protease serine 3 mRNA level in radioresistant colorectal cancer tissues.
  4. Novel Mutations in the TMPRSS3 Gene may Contribute to Taiwanese Patients with Nonsyndromic Hearing Loss.
    Title: Novel Mutations in the TMPRSS3 Gene may Contribute to Taiwanese Patients with Nonsyndromic Hearing Loss.
  5. Mutational analysis and prenatal diagnosis of TMPRSS3 gene in two Chinese families affected with deafness
    Title: [Mutational analysis and prenatal diagnosis of TMPRSS3 gene in two Chinese families affected with deafness].
  6. TMPRSS3 is an important molecule in the regulation of cell viability and cell apoptosis of HEI-OC1 cells. Its functions are dependent on the circ-Slc41a2, miR-182 and Akt cascade.
    Title: TMPRSS3 regulates cell viability and apoptosis processes of HEI-OC1 cells via regulation of the circ-Slc4a2, miR-182 and Akt cascade.
  7. These data provide evidence against TMPRSS3/GJB2 digenic inheritance of hearing loss.
    Title: Overinterpretation of high throughput sequencing data in medical genetics: first evidence against TMPRSS3/GJB2 digenic inheritance of hearing loss.
  8. Complex genomic rearrangement and a novel missense mutation in TMPRSS3 were identified in Chinese cases with prelingual hearing loss.
    Title: Identification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss.
  9. Pathogenic variants in TMPRSS3 may impact function of the spiral ganglion.
    Title: In Vivo Electrocochleography in Hybrid Cochlear Implant Users Implicates TMPRSS3 in Spiral Ganglion Function.
  10. TMPRSS3 proteolysis is linked to hair cell sterociliary mechanics and to the actin/microtubule networks that support cell motility and integrity.
    Title: Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of Corti.
Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Autosomal recessive nonsyndromic hearing loss 8
MedGen: C1832827 OMIM: 601072 GeneReviews: Genetic Hearing Loss Overview
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: TFF1

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables serine-type endopeptidase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables sodium channel regulator activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
acts_upstream_of_or_within intracellular sodium ion homeostasis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in sensory perception of sound IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum HDA PubMed 
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
transmembrane protease serine 3
Names
serine protease TADG-12
transmembrane protease, serine 3
tumor-associated differentially-expressed gene 12 protein
NP_001243246.1
NP_076927.1
NP_115780.1
NP_115781.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011629.2 RefSeqGene

    Range
    5040..29202
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001256317.3 → NP_001243246.1  transmembrane protease serine 3 isoform 4

    See identical proteins and their annotated locations for NP_001243246.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (F) uses an alternate in-frame splice site in the central coding region, compared to variant A, resulting in an isoform (4) that is 1 aa shorter than isoform 1.
    Source sequence(s)
    AB038157, AB038159, AK172842, AY358458
    Consensus CDS
    CCDS58790.1
    UniProtKB/TrEMBL
    B7WPR2
    Related
    ENSP00000494414.1, ENST00000644384.2
    Conserved Domains (3) summary
    cd00112
    Location:74 → 107
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cd00190
    Location:217 → 446
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:112 → 210
    SRCR_2; Scavenger receptor cysteine-rich domain

  2. NM_024022.4 → NP_076927.1  transmembrane protease serine 3 isoform 1

    See identical proteins and their annotated locations for NP_076927.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (A) encodes the longest isoform (1).
    Source sequence(s)
    AB038157, AK172842
    Consensus CDS
    CCDS13686.1
    UniProtKB/Swiss-Prot
    D3DSJ6, P57727, Q5USC7, Q6ZMC3
    UniProtKB/TrEMBL
    B7WPR2
    Related
    ENSP00000411013.3, ENST00000433957.7
    Conserved Domains (4) summary
    smart00020
    Location:216 → 444
    Tryp_SPc; Trypsin-like serine protease
    cd00112
    Location:74 → 107
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cd00190
    Location:217 → 447
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:112 → 210
    SRCR_2; Scavenger receptor cysteine-rich domain

  3. NM_032404.3 → NP_115780.1  transmembrane protease serine 3 isoform 2

    See identical proteins and their annotated locations for NP_115780.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (C) lacks several 5' exons but contains an alternate 5' exon, differs in the 5' UTR, and uses a downstream in-frame start codon, compared to variant A. The encoded isoform (2) is shorter at the N-terminus, compared to isoform 1.
    Source sequence(s)
    AB038159, AK172842, DA643571
    UniProtKB/Swiss-Prot
    P57727
    Related
    ENST00000474596.5
    Conserved Domains (3) summary
    smart00020
    Location:89 → 317
    Tryp_SPc; Trypsin-like serine protease
    cd00190
    Location:90 → 320
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:1 → 83
    SRCR_2; Scavenger receptor cysteine-rich domain

  4. NM_032405.2 → NP_115781.1  transmembrane protease serine 3 isoform 3

    See identical proteins and their annotated locations for NP_115781.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (D) lacks several 3' exons, but includes an alternate 3' exon, and it thus differs in the 3' coding region and 3' UTR, compared to variant A. The encoded isoform (3) has a distinct and shorter C-terminus, compared to isoform 1.
    Source sequence(s)
    AB038160
    Consensus CDS
    CCDS42939.1
    UniProtKB/TrEMBL
    Q8WY52
    Related
    ENSP00000381434.3, ENST00000398397.3
    Conserved Domains (4) summary
    smart00020
    Location:216 → 324
    Tryp_SPc; Trypsin-like serine protease
    cd00112
    Location:74 → 107
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cd00190
    Location:217 → 337
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:112 → 210
    SRCR_2; Scavenger receptor cysteine-rich domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

    Range
    42371890..42396052 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060945.1 Alternate T2T-CHM13v2.0

    Range
    40761358..40785622 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_032401.1: Suppressed sequence

    Description
    NM_032401.1: This RefSeq was permanently suppressed because it is now thought that this transcript does not encode a protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P57727.2 GenPept UniProtKB/Swiss-Prot:P57727

Gene LinkOut

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