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

    Gene ID: 3699, updated on 27-Dec-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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 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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