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    ITIH4 inter-alpha-trypsin inhibitor heavy chain 4 [ Homo sapiens (human) ]

    Gene ID: 3700, updated on 3-Nov-2024

    Summary

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    Official Symbol
    ITIH4provided by HGNC
    Official Full Name
    inter-alpha-trypsin inhibitor heavy chain 4provided by HGNC
    Primary source
    HGNC:HGNC:6169
    See related
    Ensembl:ENSG00000055955 MIM:600564; AllianceGenome:HGNC:6169
    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
    H4P; IHRP; GP120; PK120; ITIHL1; PK-120; ITI-HC4
    Summary
    The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
    Expression
    Restricted expression toward liver (RPKM 556.7) See more
    Orthologs
    mouse all
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    Genomic context

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    See ITIH4 in Genome Data Viewer
    Location:
    3p21.1
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (52812962..52830672, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (52845872..52863582, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52846978..52864688, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:52812248-52813447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19948 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52828410-52829299 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 3 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 ITIH4 antisense RNA 1 Neighboring gene STIMATE-MUSTN1 readthrough Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_70612 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52873819-52874320 Neighboring gene musculoskeletal, embryonic nuclear protein 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52878501-52879001 Neighboring gene STIM activating enhancer Neighboring gene microRNA 8064

    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 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. cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-sensitive glycoprotein. Nishimura H, et al. FEBS Lett, 1995 Jan 3. PMID 7805892
    2. Opposing roles of inter-α-trypsin inhibitor heavy chain 4 in recurrent pregnancy loss. Li L, et al. EBioMedicine, 2018 Nov. PMID 30348621, Free PMC Article
    3. ITI-H4, as a biomarker in the serum of recurrent pregnancy loss (RPL) patients. Kim MS, et al. Mol Biosyst, 2011 May. PMID 21331437
    4. Serological targeted analysis of an ITIH4 peptide isoform: a preterm birth biomarker and its associated SNP implications. Tan Z, et al. J Genet Genomics, 2015 Sep 20. PMID 26408095, Free PMC Article
    5. Inter-alpha-trypsin inhibitor heavy chain 4: a novel biomarker for environmental exposure to particulate air pollution in patients with chronic obstructive pulmonary disease. Lee KY, et al. Int J Chron Obstruct Pulmon Dis, 2015. PMID 25977605, Free PMC Article

    See all (74) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Translatome profiling reveals Itih4 as a novel smooth muscle cell-specific gene in atherosclerosis.
      Title: Translatome profiling reveals Itih4 as a novel smooth muscle cell-specific gene in atherosclerosis.
    2. Serum interalpha-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis.
      Title: Serum interα-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis.
    3. Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique and May Contribute to CRF01_AE Transmission Among Men Who Have Sex with Men in China and Thailand.
      Title: Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique and May Contribute to CRF01_AE Transmission Among Men Who Have Sex with Men in China and Thailand.
    4. PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4.
      Title: PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4.
    5. Serum ITIH4 in coronary heart disease: a potential anti-inflammatory biomarker related to stenosis degree and risk of major adverse cardiovascular events.
      Title: Serum ITIH4 in coronary heart disease: a potential anti-inflammatory biomarker related to stenosis degree and risk of major adverse cardiovascular events.
    6. Longitudinal change of serum inter-alpha-trypsin inhibitor heavy chain H4, and its correlation with inflammation, multiorgan injury, and death risk in sepsis.
      Title: Longitudinal change of serum inter-alpha-trypsin inhibitor heavy chain H4, and its correlation with inflammation, multiorgan injury, and death risk in sepsis.
    7. Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.
      Title: Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.
    8. ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.
      Title: ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.
    9. ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.
      Title: ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.
    10. Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.
      Title: Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.
    Submit: New GeneRIF Correction See all GeneRIFs (31)

    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
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
    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)

    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: MUSTN1

    Homology

    Clone Names

    • DKFZp686G21125

    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 acute-phase response IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in hyaluronan metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to cytokine IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in blood microparticle HDA PubMed 
    located_in collagen-containing extracellular matrix HDA PubMed 
    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 plasma membrane IEA
    Inferred from Electronic Annotation
    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 H4
    Names
    ITI heavy chain H4
    inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein)
    inter-alpha-inhibitor heavy chain 4
    inter-alpha-trypsin inhibitor family heavy chain-related protein
    inter-alpha-trypsin inhibitor heavy chain family member 4
    inter-alpha-trypsin inhibitor, heavy chain-like, 1
    plasma kallikrein-sensitive glycoprotein 120

    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_016006.2 RefSeqGene

      Range
      5030..22740
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166449.2 → NP_001159921.1  inter-alpha-trypsin inhibitor heavy chain H4 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC006254, AK298412, AW291001, BC136392
      Consensus CDS
      CCDS54596.1
      UniProtKB/TrEMBL
      B7Z544
      Related
      ENSP00000384425.1, ENST00000406595.5
      Conserved Domains (5) summary
      smart00609
      Location:21 → 148
      VIT; Vault protein Inter-alpha-Trypsin domain
      cd01461
      Location:271 → 452
      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 ...
      TIGR03788
      Location:40 → 592
      marine_srt_targ; marine proteobacterial sortase target protein
      pfam06668
      Location:736 → 898
      ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
      cl17185
      Location:703 → 730
      LPLAT; Lysophospholipid acyltransferases (LPLATs) of glycerophospholipid biosynthesis

    2. NM_002218.5 → NP_002209.2  inter-alpha-trypsin inhibitor heavy chain H4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_002209.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC006254, AW291001, BC136392, BC136393
      Consensus CDS
      CCDS2865.1
      UniProtKB/Swiss-Prot
      B7Z545, E9PGN5, Q14624, Q15135, Q9P190, Q9UQ54
      UniProtKB/TrEMBL
      B2RMS9
      Related
      ENSP00000266041.4, ENST00000266041.9
      Conserved Domains (5) summary
      smart00609
      Location:21 → 148
      VIT; Vault protein Inter-alpha-Trypsin domain
      cd01461
      Location:271 → 452
      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 ...
      TIGR03788
      Location:40 → 626
      marine_srt_targ; marine proteobacterial sortase target protein
      pfam06668
      Location:766 → 928
      ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
      cl17185
      Location:733 → 760
      LPLAT; Lysophospholipid acyltransferases (LPLATs) of glycerophospholipid biosynthesis

    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
      52812962..52830672 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      52845872..52863582 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14624.4 GenPept UniProtKB/Swiss-Prot:Q14624

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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