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ITIH3 inter-alpha-trypsin inhibitor heavy chain 3 [ Homo sapiens (human) ]

Gene ID: 3699, updated on 27-Nov-2024

Summary

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Official Symbol
ITIH3provided by HGNC
Official Full Name
inter-alpha-trypsin inhibitor heavy chain 3provided by HGNC
Primary source
HGNC:HGNC:6168
See related
Ensembl:ENSG00000162267 MIM:146650; AllianceGenome:HGNC:6168
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
H3P; SHAP; ITI-HC3
Summary
This gene encodes the heavy chain subunit of the pre-alpha-trypsin inhibitor complex. This complex may stabilize the extracellular matrix through its ability to bind hyaluronic acid. Polymorphisms of this gene may be associated with increased risk for schizophrenia and major depressive disorder. This gene is present in an inter-alpha-trypsin inhibitor family gene cluster on chromosome 3. [provided by RefSeq, Jul 2015]
Expression
Restricted expression toward liver (RPKM 228.8) See more
Orthologs
mouse all
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Genomic context

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See ITIH3 in Genome Data Viewer
Location:
3p21.1
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (52794796..52808797)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (52827705..52841707)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52828812..52842813)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene NIMA related kinase 4 Neighboring gene AKTIP pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52804733-52805250 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:52812248-52813447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19948 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52828410-52829299 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 1 Neighboring gene uncharacterized LOC124906240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52853641-52854629 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:52858275-52858432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52861432-52862040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52862041-52862648 Neighboring gene STIMATE-MUSTN1 readthrough Neighboring gene inter-alpha-trypsin inhibitor heavy chain 4 Neighboring gene ITIH4 antisense RNA 1 Neighboring gene musculoskeletal, embryonic nuclear protein 1

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. The role of the ITIH3 rs2535629 variant in antipsychotic response. Brandl EJ, et al. Schizophr Res, 2016 Oct. PMID 27396837
  2. A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction. Ebana Y, et al. J Hum Genet, 2007. PMID 17211523
  3. Identification of sonic hedgehog-responsive genes using cDNA microarray. Kato M, et al. Biochem Biophys Res Commun, 2001 Nov 30. PMID 11716497
  4. The low pH in trans-Golgi triggers autocatalytic cleavage of pre-alpha -inhibitor heavy chain precursor. Thuveson M, et al. J Biol Chem, 2000 Oct 6. PMID 10893227
  5. [Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix]. Cuvelier A, et al. Rev Mal Respir, 2000 Apr. PMID 10859762

See all (59) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A psychiatric disorder risk polymorphism of ITIH3 is associated with multiple neuroimaging phenotypes in young healthy adults.
    Title: A psychiatric disorder risk polymorphism of ITIH3 is associated with multiple neuroimaging phenotypes in young healthy adults.
  2. Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression.
    Title: Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression.
  3. A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population.
    Title: A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population.
  4. Integrative analyses indicate an association between ITIH3 polymorphisms with autism spectrum disorder.
    Title: Integrative analyses indicate an association between ITIH3 polymorphisms with autism spectrum disorder.
  5. ITIH3 SNPs rs2535629 and rs736408 were studied in pregnant depressed Japanese women. Neither was related to depressive symptoms during pregnancy.The GCCT haplotype of rs2535629, rs736408, rs3821831, and rs2239547 was significantly positively associated with depressive symptoms during pregnancy.
    Title: ITIH3 and ITIH4 polymorphisms and depressive symptoms during pregnancy in Japan: the Kyushu Okinawa Maternal and Child Health Study.
  6. ITIH3 rs2535629 SNP was genotyped in N=256 patients receiving various antipsychotics for up to 26weeks. Study found no association of genotype with overall changes in Brief Psychiatric Rating Scale scores, but greater improvement of negative symptoms in minor allele carriers indicates that rs2535629 may help to identify a subset of schizophrenia patients with better treatment response to clozapine.
    Title: The role of the ITIH3 rs2535629 variant in antipsychotic response.
  7. confirmed the association of schizophrenia with ITIH3/4 in a Han Chinese population
    Title: Loci with genome-wide associations with schizophrenia in the Han Chinese population.
  8. A novel association between suicide attempt and the ITIH3/4-region in a combined group of patients with bipolar disorder, schizophrenia and related psychosis spectrum disorders.
    Title: Association analysis between suicidal behaviour and candidate genes of bipolar disorder and schizophrenia.
  9. Study showed the association of a polymorphism (rs2535629) of ITIH3 with psychiatric disorders in an Asian population and that rs2535629 influences the susceptibility to psychiatric disorders by affecting the expression level of GLT8D1
    Title: ITIH3 polymorphism may confer susceptibility to psychiatric disorders by altering the expression levels of GLT8D1.
  10. This study demonistrated that Genome-wide significant associations in schizophrenia to ITIH3/4 and extensive replication of associations reported by the Schizophrenia.
    Title: Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC.
Submit: New GeneRIF Correction See all GeneRIFs (15)

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

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
EBI GWAS Catalog
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
EBI GWAS Catalog
Genome-wide association study identifies five new schizophrenia loci.
EBI GWAS Catalog
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
EBI GWAS Catalog
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
EBI GWAS Catalog

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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in hyaluronan metabolic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in platelet dense granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
inter-alpha-trypsin inhibitor heavy chain H3
Names
ITI heavy chain H3
inter-alpha (globulin) inhibitor H3
inter-alpha (globulin) inhibitor, H3 polypeptide
inter-alpha-inhibitor heavy chain 3
pre-alpha (globulin) inhibitor, H3 polypeptide
serum-derived hyaluronan-associated protein

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.

mRNA and Protein(s)

  1. NM_001392019.1 → NP_001378948.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 1 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Consensus CDS
    CCDS93288.1
    UniProtKB/TrEMBL
    A0A994J439
    Related
    ENSP00000515492.1, ENST00000703834.1
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:721 → 908
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  2. NM_001392020.1 → NP_001378949.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 2 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:718 → 905
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  3. NM_001392021.1 → NP_001378950.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 3 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:684 → 879
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  4. NM_001392022.1 → NP_001378951.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 5 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:681 → 868
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  5. NM_001392023.1 → NP_001378952.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 6 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Conserved Domains (3) summary
    smart00609
    Location:34 → 151
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:274 → 455
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:677 → 864
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  6. NM_001392024.1 → NP_001378953.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 7 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:673 → 860
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  7. NM_001392025.1 → NP_001378954.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 8 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:670 → 857
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  8. NM_001392026.1 → NP_001378955.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 9 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    UniProtKB/TrEMBL
    B4DPQ4
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 461
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:622 → 809
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  9. NM_001392027.1 → NP_001378956.1  inter-alpha-trypsin inhibitor heavy chain H3 isoform 10 precursor

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Consensus CDS
    CCDS93287.1
    UniProtKB/TrEMBL
    B4DPQ4, E7ET33
    Related
    ENSP00000413922.2, ENST00000416872.6
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:530 → 679
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  10. NM_002217.4 → NP_002208.3  inter-alpha-trypsin inhibitor heavy chain H3 isoform 4 preproprotein

    See identical proteins and their annotated locations for NP_002208.3

    Status: REVIEWED

    Source sequence(s)
    AC006254
    Consensus CDS
    CCDS46845.1
    UniProtKB/Swiss-Prot
    Q06033, Q3B7H5, Q53F06, Q6LAM2, Q99085
    Related
    ENSP00000415769.2, ENST00000449956.3
    Conserved Domains (3) summary
    smart00609
    Location:29 → 158
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:281 → 462
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    pfam06668
    Location:684 → 871
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

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

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    52794796..52808797
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    52827705..52841707
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q06033.2 GenPept UniProtKB/Swiss-Prot:Q06033

Gene LinkOut

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