TMPRSS6 transmembrane serine protease 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TMPRSS6provided by HGNC
Official Full Name: transmembrane serine protease 6provided by HGNC
Primary source: HGNC:HGNC:16517
See related: Ensembl:ENSG00000187045 MIM:609862; AllianceGenome:HGNC:16517
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: MT2; IRIDA
Summary: The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Expression: Biased expression in liver (RPKM 19.4), stomach (RPKM 1.7) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 22q12.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (37065436..37110536, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (37525034..37570488, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (37461476..37505753, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel TMPRSS6 variants and their impact on iron-refractory iron deficiency anaemia in pregnancy: A North Indian genotype phenotype study.
Title: Novel TMPRSS6 variants and their impact on iron-refractory iron deficiency anaemia in pregnancy: A North Indian genotype phenotype study.
Genetic analysis of TMPRSS6 catalytic domain variants in Mexican patients with iron treatment refractoriness.
Title: Genetic analysis of TMPRSS6 catalytic domain variants in Mexican patients with iron treatment refractoriness.
A functional interplay between the two BMP-SMAD pathway inhibitors TMPRSS6 and FKBP12 regulates hepcidin expression in vivo.
Title: A functional interplay between the two BMP-SMAD pathway inhibitors TMPRSS6 and FKBP12 regulates hepcidin expression in vivo.
The role of TMPRSS6 gene polymorphism in iron resistance iron deficiency anaemia (IRIDA): a systematic review.
Title: The role of TMPRSS6 gene polymorphism in iron resistance iron deficiency anaemia (IRIDA): a systematic review.
The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study).
Title: The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study).
Possible effect of OAS1 and TMPRSS6 but not DPP4 and ZNF335 polymorphisms on COVID-19 severity in the Czech population.
Title: Possible effect of OAS1 and TMPRSS6 but not DPP4 and ZNF335 polymorphisms on COVID-19 severity in the Czech population.
Anaemia and iron deficiency associate with polymorphism TMPRSS6 rs855791 in Brazilian children attending day care centres.
Title: Anaemia and iron deficiency associate with polymorphism TMPRSS6 rs855791 in Brazilian children attending day care centres.
Genomics of iron refractory iron deficiency anemia phenotype reveals a spectrum of novel pathogenic biallelic and monoallelic TMPRSS6 variants and rare overlapping disorders.
Title: Genomics of iron refractory iron deficiency anemia phenotype reveals a spectrum of novel pathogenic biallelic and monoallelic TMPRSS6 variants and rare overlapping disorders.
TMPRSS6 gene mutations in six Saudi families with iron refractory iron deficiency anemia.
Title: TMPRSS6 gene mutations in six Saudi families with iron refractory iron deficiency anemia.
Common Single Nucleotide Polymorphism of TMPRSS6, an Iron Regulation Gene, Associated with Variable Red Blood Cell Indices in Deletional alpha-Globin Genotypes.
Title: Common Single Nucleotide Polymorphism of TMPRSS6, an Iron Regulation Gene, Associated with Variable Red Blood Cell Indices in Deletional α-Globin Genotypes.

Submit: New GeneRIF Correction See all GeneRIFs (110)

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
Iron-refractory iron deficiency anemia MedGen: C0085576 OMIM: 206200 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association analysis of serum iron concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of red blood cell traits using the electronic medical record. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 10 genomic loci influence hemoglobin A&#x000e2;&#x00082;&#x00081;(C) levels via glycemic and nonglycemic pathways. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Sequence variants in three loci influence monocyte counts and erythrocyte volume. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seventy-five genetic loci influencing the human red blood cell. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metalloendopeptidase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in collagen catabolic process	TAS Traceable Author Statement more info
involved_in extracellular matrix disassembly	TAS Traceable Author Statement more info
involved_in intracellular iron ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in membrane protein proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in multicellular organismal-level iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in self proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: transmembrane protease serine 6

Names: matriptase-2; membrane-bound mosaic serine proteinase matriptase-2; transmembrane protease, serine 6; type II transmembrane serine protease 6

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

NG_012856.2 RefSeqGene

Range

4851..49128

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1128

mRNA and Protein(s)

NM_001289000.2 → NP_001275929.1 transmembrane protease serine 6 isoform 1

See identical proteins and their annotated locations for NP_001275929.1

Status: REVIEWED

Source sequence(s)

AL022314, AW295507

Consensus CDS

CCDS74857.1

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Related

ENSP00000384964.1, ENST00000406856.7

Conserved Domains (5) summary

cd00041
Location:326 → 440

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00112
Location:486 → 516

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:568 → 822

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 ...

pfam00057
Location:520 → 557

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 177

SEA; SEA domain
NM_001289001.2 → NP_001275930.1 transmembrane protease serine 6 isoform 3

See identical proteins and their annotated locations for NP_001275930.1

Status: REVIEWED

Source sequence(s)

AL022314, AW295507, AY358398

Consensus CDS

CCDS74856.1

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Related

ENSP00000385453.1, ENST00000406725.6

Conserved Domains (5) summary

cd00041
Location:326 → 440

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00112
Location:486 → 516

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:568 → 800

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 ...

pfam00057
Location:520 → 557

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 134

SEA; SEA domain
NM_001374504.1 → NP_001361433.1 transmembrane protease serine 6 isoform 3

Status: REVIEWED

Source sequence(s)

AL022314

Consensus CDS

CCDS74856.1

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Related

ENSP00000501573.1, ENST00000676104.1

Conserved Domains (5) summary

cd00041
Location:326 → 440

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00112
Location:486 → 516

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:568 → 800

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 ...

pfam00057
Location:520 → 557

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 134

SEA; SEA domain
NM_153609.4 → NP_705837.2 transmembrane protease serine 6 isoform 3

Status: REVIEWED

Source sequence(s)

AL022314

Consensus CDS

CCDS74856.1

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Related

ENSP00000334962.6, ENST00000346753.9

Conserved Domains (5) summary

cd00041
Location:326 → 440

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00112
Location:486 → 516

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:568 → 800

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 ...

pfam00057
Location:520 → 557

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 134

SEA; SEA domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

37065436..37110536 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024452167.2 → XP_024307935.1 transmembrane protease serine 6 isoform X1

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Related

ENSP00000371211.2, ENST00000381792.6

Conserved Domains (5) summary

cd00041
Location:326 → 440

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00112
Location:486 → 516

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:568 → 822

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 ...

pfam00057
Location:520 → 557

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 177

SEA; SEA domain
XM_047441170.1 → XP_047297126.1 transmembrane protease serine 6 isoform X3
XM_011529989.3 → XP_011528291.1 transmembrane protease serine 6 isoform X2

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Conserved Domains (6) summary

smart00020
Location:423 → 675

Tryp_SPc; Trypsin-like serine protease

cd00112
Location:342 → 372

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:424 → 678

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 ...

pfam00057
Location:376 → 413

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 134

SEA; SEA domain

cl00049
Location:182 → 296

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
XM_047441171.1 → XP_047297127.1 transmembrane protease serine 6 isoform X3
XM_024452168.2 → XP_024307936.1 transmembrane protease serine 6 isoform X1

UniProtKB/Swiss-Prot

B0QYB4, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IU80, Q8IUE2, Q8IXV8

Conserved Domains (5) summary

cd00041
Location:326 → 440

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00112
Location:486 → 516

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:568 → 822

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 ...

pfam00057
Location:520 → 557

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:77 → 177

SEA; SEA domain

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

37525034..37570488 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054325197.1 → XP_054181172.1 transmembrane protease serine 6 isoform X1
XM_054325199.1 → XP_054181174.1 transmembrane protease serine 6 isoform X3
XM_054325198.1 → XP_054181173.1 transmembrane protease serine 6 isoform X2
XM_054325200.1 → XP_054181175.1 transmembrane protease serine 6 isoform X3
XM_054325196.1 → XP_054181171.1 transmembrane protease serine 6 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_153019.2: Suppressed sequence

Description

NM_153019.2: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.