HTRA1 HtrA serine peptidase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HTRA1provided by HGNC
Official Full Name: HtrA serine peptidase 1provided by HGNC
Primary source: HGNC:HGNC:9476
See related: Ensembl:ENSG00000166033 MIM:602194; AllianceGenome:HGNC:9476
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: L56; HtrA; ARMD7; ORF480; PRSS11; CARASIL; CADASIL2
Summary: This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]
Expression: Broad expression in ovary (RPKM 155.6), gall bladder (RPKM 130.0) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q26.13

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (122461553..122514907)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (123357406..123410753)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (124221069..124274423)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

HTRA1-driven detachment of type I collagen from endoplasmic reticulum contributes to myocardial fibrosis in dilated cardiomyopathy.
Title: HTRA1-driven detachment of type I collagen from endoplasmic reticulum contributes to myocardial fibrosis in dilated cardiomyopathy.
Exploring the contribution of ARMS2 and HTRA1 genetic risk factors in age-related macular degeneration.
Title: Exploring the contribution of ARMS2 and HTRA1 genetic risk factors in age-related macular degeneration.
HTRA1 promotes EMT through the HDAC6/Ac-alpha-tubulin pathway in human GBM cells.
Title: HTRA1 promotes EMT through the HDAC6/Ac-α-tubulin pathway in human GBM cells.
Critical Dependence on Area in Relationship between ARMS2/HTRA1 Genotype and Faster Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report Number 33.
Title: Critical Dependence on Area in Relationship between ARMS2/HTRA1 Genotype and Faster Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report Number 33.
Spontaneous malignant transformation of trigeminal schwannoma: consideration of responsible gene alterations for tumorigenesis-a case report.
Title: Spontaneous malignant transformation of trigeminal schwannoma: consideration of responsible gene alterations for tumorigenesis-a case report.
Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1.
Title: Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1.
Upregulation of HTRA1 mediated by the lncRNA NEAT1/miR-141-3p axis contributes to endometriosis development through activating NLRP3 inflammasome-mediated pyroptotic cell death and cellular inflammation.
Title: Upregulation of HTRA1 mediated by the lncRNA NEAT1/miR-141-3p axis contributes to endometriosis development through activating NLRP3 inflammasome-mediated pyroptotic cell death and cellular inflammation.
Reticular Pseudodrusen Status, ARMS2/HTRA1 Genotype, and Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report 32.
Title: Reticular Pseudodrusen Status, ARMS2/HTRA1 Genotype, and Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report 32.
Disentangling the Impact of Reticular Pseudodrusen Phenotype and the ARMS2/HTRA1 Risk Allele in Geographic Atrophy: The AREDS 2 Study Report 32.
Title: Disentangling the Impact of Reticular Pseudodrusen Phenotype and the ARMS2/HTRA1 Risk Allele in Geographic Atrophy: The AREDS 2 Study Report 32.
Clinical features and pathogenicity assessment in patients with HTRA1-autosomal dominant disease.
Title: Clinical features and pathogenicity assessment in patients with HTRA1-autosomal dominant disease.

Submit: New GeneRIF Correction See all GeneRIFs (282)

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
Age related macular degeneration 7 MedGen: C1857813 OMIM: 610149 GeneReviews: Not available	Compare labs
CARASIL syndrome MedGen: C1838577 OMIM: 600142 GeneReviews: HTRA1 Disorder	Compare labs
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 MedGen: C4225211 OMIM: 616779 GeneReviews: HTRA1 Disorder	Compare labs

EBI GWAS Catalog

Description
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3. EBI GWAS Catalog EBI GWAS CatalogPubMed
Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes. EBI GWAS Catalog EBI GWAS CatalogPubMed
HTRA1 promoter polymorphism in wet age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seven new loci associated with age-related macular degeneration. 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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Markers

RH69852 (e-PCR)
- UniSTS:51202

G20611 (e-PCR)
- UniSTS:56333

A005Z02 (e-PCR)
- UniSTS:56334

IB2169 (e-PCR)
- UniSTS:49785

G06946 (e-PCR)
- UniSTS:35768

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables growth factor binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular function activator activity	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type peptidase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in chorionic trophoblast cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in placenta development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in programmed cell death	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	TAS Traceable Author Statement more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: serine protease HTRA1

Names: IGFBP5-protease; high-temperature requirement A serine peptidase 1; protease, serine, 11 (IGF binding)

NP_002766.1

EC 3.4.21.-

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_011554.1 RefSeqGene

Range

5029..58383

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002775.5 → NP_002766.1 serine protease HTRA1 precursor

See identical proteins and their annotated locations for NP_002766.1

Status: REVIEWED

Source sequence(s)

DA633502, Y07921

Consensus CDS

CCDS7630.1

UniProtKB/Swiss-Prot

D3DRE4, Q92743, Q9UNS5

Related

ENSP00000357980.3, ENST00000368984.8

Conserved Domains (5) summary

smart00121
Location:35 → 111

IB; Insulin growth factor-binding protein homologues

smart00280
Location:115 → 155

KAZAL; Kazal type serine protease inhibitors

COG0265
Location:154 → 480

DegQ; Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones]

cd00987
Location:382 → 473

PDZ_serine_protease; PDZ domain of trypsin-like serine proteases, such as DegP/HtrA, which are oligomeric proteins involved in heat-shock response, chaperone function, and apoptosis. May be responsible for substrate recognition and/or binding, as most PDZ domains bind ...

pfam13365
Location:204 → 342

Trypsin_2; Trypsin-like peptidase domain