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 chr... See more...

Aliases for ITIH3 Gene

Aliases for ITIH3 Gene

  • Inter-Alpha-Trypsin Inhibitor Heavy Chain 3 2 3 5
  • Inter-Alpha-Trypsin Inhibitor Heavy Chain H3 2 3 4
  • Inter-Alpha (Globulin) Inhibitor, H3 Polypeptide 2 3
  • Pre-Alpha (Globulin) Inhibitor, H3 Polypeptide 2 3
  • Serum-Derived Hyaluronan-Associated Protein 3 4
  • Inter-Alpha (Globulin) Inhibitor H3 2 3
  • Inter-Alpha-Inhibitor Heavy Chain 3 3 4
  • ITI Heavy Chain H3 3 4
  • ITI-HC3 3 4
  • SHAP 3 4
  • H3P 2 3
  • ITIH3 5

External Ids for ITIH3 Gene

Previous GeneCards Identifiers for ITIH3 Gene

  • GC03P051920
  • GC03P052080
  • GC03P052683
  • GC03P052786
  • GC03P052803
  • GC03P052828

Summaries for ITIH3 Gene

Entrez Gene Summary for ITIH3 Gene

  • 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]

GeneCards Summary for ITIH3 Gene

ITIH3 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 3) is a Protein Coding gene. Diseases associated with ITIH3 include Schizophrenia and Major Depressive Disorder. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Cell adhesion_Cell-matrix glycoconjugates. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity. An important paralog of this gene is ITIH1.

UniProtKB/Swiss-Prot Summary for ITIH3 Gene

  • May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.

Gene Wiki entry for ITIH3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ITIH3 Gene

Genomics for ITIH3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ITIH3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J052794 Promoter/Enhancer 1.1 EPDnew Ensembl 605.9 -0.3 -267 1.4 HNRNPL GATAD2A REST RXRB IRF2 SP1 CEBPA SOX13 FOXA2 YY1 ITIH3 PBRM1 STAB1 lnc-NEK4-1 ITIH1
GH03J052793 Enhancer 0.3 Ensembl 600.7 -1.5 -1467 0.6 YY1 ITIH3 PBRM1 lnc-NEK4-1 ITIH1
GH03J052769 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 12.8 -24.2 -24199 2.7 HNRNPL GATAD2A REST RFX1 ZNF692 POLR2A LARP7 PRDM1 ZNF143 RELA NEK4 lnc-ITIH1-3 PBRM1 RFT1 ITIH3 RRP9 ITIH4-AS1 ITIH4 ENSG00000243696 SNORD69
GH03J052840 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE dbSUPER 10.8 +48.9 48882 7.1 GATAD2A CTCF REST SOX13 PKNOX1 SP1 CEBPA CEBPB RUNX3 FOXA2 lnc-TMEM110-MUSTN1-1-002 STIMATE ITIH4 RFT1 ITIH1 ITIH3 GLYCTK RPL29 MIR8064 lnc-TMEM110-MUSTN1-1-001
GH03J052274 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 4.5 -511.9 -511913 17.3 HNRNPL CREB1 GATAD2A CTCF ATF7 PRDM10 REST ZNF629 TFE3 SOX13 GLYCTK WDR82 DNAH1 PBRM1 ENSG00000243224 PPM1M TWF2 ITIH4 RFT1 ABHD14B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ITIH3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ITIH3

Top Transcription factor binding sites by QIAGEN in the ITIH3 gene promoter:
  • ARP-1
  • Egr-3
  • GR
  • GR-alpha
  • MIF-1
  • NF-E2
  • NF-E2 p45
  • Pax-2
  • Pax-2a
  • Pax-5

Genomic Locations for ITIH3 Gene

Genomic Locations for ITIH3 Gene
chr3:52,794,768-52,809,009
(GRCh38/hg38)
Size:
14,242 bases
Orientation:
Plus strand
chr3:52,828,784-52,843,025
(GRCh37/hg19)
Size:
14,242 bases
Orientation:
Plus strand

Genomic View for ITIH3 Gene

Genes around ITIH3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ITIH3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ITIH3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ITIH3 Gene

Proteins for ITIH3 Gene

  • Protein details for ITIH3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q06033-ITIH3_HUMAN
    Recommended name:
    Inter-alpha-trypsin inhibitor heavy chain H3
    Protein Accession:
    Q06033
    Secondary Accessions:
    • Q3B7H5
    • Q53F06
    • Q6LAM2
    • Q99085

    Protein attributes for ITIH3 Gene

    Size:
    890 amino acids
    Molecular mass:
    99849 Da
    Quaternary structure:
    • I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (H1, H2 or H3) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of H1, H2 and bikunin, inter-alpha-like inhibitor (I-alpha-LI) of H2 and bikunin, and pre-alpha-inhibitor (P-alpha-I) of H3 and bikunin.
    SequenceCaution:
    • Sequence=CAA32821.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA47439.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for ITIH3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ITIH3 Gene

Post-translational modifications for ITIH3 Gene

  • Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.
  • Glycosylation at Asn91 and Asn580
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ITIH3_HUMAN (1421)

Other Protein References for ITIH3 Gene

No data available for DME Specific Peptides for ITIH3 Gene

Domains & Families for ITIH3 Gene

Gene Families for ITIH3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for ITIH3 Gene

InterPro:
Blocks:
  • Von Willebrand factor type A domain signature
  • Inter-alpha-trypsin inhibitor heavy chain, C-terminal
  • Vault protein inter-alpha-trypsin
ProtoNet:

Suggested Antigen Peptide Sequences for ITIH3 Gene

GenScript: Design optimal peptide antigens:
  • Serum-derived hyaluronan-associated protein (ITIH3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q06033

UniProtKB/Swiss-Prot:

ITIH3_HUMAN :
  • Belongs to the ITIH family.
Family:
  • Belongs to the ITIH family.
genes like me logo Genes that share domains with ITIH3: view

Function for ITIH3 Gene

Molecular function for ITIH3 Gene

UniProtKB/Swiss-Prot Function:
May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.
GENATLAS Biochemistry:
trypsin inhibitor,inter-alpha- (protein HC),heavy chain 3

Phenotypes From GWAS Catalog for ITIH3 Gene

Gene Ontology (GO) - Molecular Function for ITIH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity TAS 2465147
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with ITIH3: view
genes like me logo Genes that share phenotypes with ITIH3: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ITIH3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for ITIH3 Gene

Localization for ITIH3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ITIH3 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ITIH3 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for ITIH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0031089 platelet dense granule lumen TAS --
GO:0070062 extracellular exosome HDA 23533145
genes like me logo Genes that share ontologies with ITIH3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ITIH3 Gene

Pathways & Interactions for ITIH3 Gene

genes like me logo Genes that share pathways with ITIH3: view

Pathways by source for ITIH3 Gene

1 GeneGo (Thomson Reuters) pathway for ITIH3 Gene
  • Cell adhesion_Cell-matrix glycoconjugates

Gene Ontology (GO) - Biological Process for ITIH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002576 platelet degranulation TAS --
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0030212 hyaluronan metabolic process IEA --
genes like me logo Genes that share ontologies with ITIH3: view

No data available for SIGNOR curated interactions for ITIH3 Gene

Drugs & Compounds for ITIH3 Gene

(5) Drugs for ITIH3 Gene - From: DrugBank and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Zinc Approved, Investigational Pharma Target 1594
zinc acetate Approved, Investigational Pharma Target 0
Zinc chloride Approved, Investigational Pharma Target, binder 0
Zinc sulfate, unspecified form Approved, Experimental Pharma Target, binder 0
Clozapine Approved Pharma Antagonist, Allosteric regulator, Positive, Agonist, Full agonist, Inverse agonist Antipsychotic medication 136
genes like me logo Genes that share compounds with ITIH3: view

Transcripts for ITIH3 Gene

mRNA/cDNA for ITIH3 Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ITIH3

Alternative Splicing Database (ASD) splice patterns (SP) for ITIH3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b · 10c ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b · 14c ^ 15 ^ 16 ^
SP1: - -
SP2:
SP3: -
SP4: -
SP5: -
SP6:
SP7:
SP8: - -
SP9:
SP10:

ExUns: 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:

Relevant External Links for ITIH3 Gene

GeneLoc Exon Structure for
ITIH3

Expression for ITIH3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ITIH3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ITIH3 Gene

This gene is overexpressed in Liver (x45.3).

Protein differential expression in normal tissues from HIPED for ITIH3 Gene

This gene is overexpressed in Serum (35.0), Plasma (12.9), and Synovial fluid (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ITIH3 Gene



Protein tissue co-expression partners for ITIH3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ITIH3

SOURCE GeneReport for Unigene cluster for ITIH3 Gene:

Hs.76716

Evidence on tissue expression from TISSUES for ITIH3 Gene

  • Liver(4.9)
  • Blood(4.4)
  • Bone marrow(4.2)
  • Heart(2)
genes like me logo Genes that share expression patterns with ITIH3: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ITIH3 Gene

Orthologs for ITIH3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ITIH3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ITIH3 30 31
  • 99.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ITIH3 30 31
  • 88.35 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ITIH3 30 31
  • 87.53 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Itih3 30 17 31
  • 84.68 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Itih3 30
  • 84.12 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 74 (a)
OneToMany
-- 31
  • 70 (a)
OneToMany
-- 31
  • 57 (a)
OneToMany
-- 31
  • 52 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia ITIH3 31
  • 49 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ITIH3 30
  • 66.31 (n)
-- 31
  • 64 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 64 (a)
ManyToMany
-- 31
  • 60 (a)
ManyToMany
African clawed frog
(Xenopus laevis)
Amphibia Xl.5040 30
Zebrafish
(Danio rerio)
Actinopterygii LOC564761 30
  • 58.81 (n)
zgc:110377 31
  • 49 (a)
ManyToMany
CR558302.3 31
  • 48 (a)
ManyToMany
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9191 30
Species where no ortholog for ITIH3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ITIH3 Gene

ENSEMBL:
Gene Tree for ITIH3 (if available)
TreeFam:
Gene Tree for ITIH3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ITIH3: view image

Paralogs for ITIH3 Gene

Paralogs for ITIH3 Gene

(6) SIMAP similar genes for ITIH3 Gene using alignment to 2 proteins:

  • ITIH3_HUMAN
  • E7ET33_HUMAN
genes like me logo Genes that share paralogs with ITIH3: view

Variants for ITIH3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ITIH3 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
739678 Likely Benign: not provided 52,806,989(+) C/T SYNONYMOUS_VARIANT
740600 Benign: not provided 52,797,174(+) C/T SYNONYMOUS_VARIANT
767914 Benign: not provided 52,807,095(+) A/G MISSENSE_VARIANT
775199 Benign: not provided 52,802,517(+) G/A MISSENSE_VARIANT
778084 Benign: not provided 52,796,531(+) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for ITIH3 Gene

Structural Variations from Database of Genomic Variants (DGV) for ITIH3 Gene

Variant ID Type Subtype PubMed ID
esv2762328 CNV loss 21179565
esv3452194 CNV duplication 20981092
nsv1010761 CNV gain 25217958
nsv3822 CNV insertion 18451855
nsv508928 CNV insertion 20534489
nsv834698 CNV gain 17160897

Variation tolerance for ITIH3 Gene

Residual Variation Intolerance Score: 96.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.25; 76.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ITIH3 Gene

Human Gene Mutation Database (HGMD)
ITIH3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ITIH3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ITIH3 Gene

Disorders for ITIH3 Gene

MalaCards: The human disease database

(3) MalaCards diseases for ITIH3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
schizophrenia
  • sczd
major depressive disorder
  • mdd
bipolar disorder
  • major affective disorder 1
- elite association - COSMIC cancer census association via MalaCards
Search ITIH3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ITIH3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ITIH3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ITIH3 Gene

Publications for ITIH3 Gene

  1. A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction. (PMID: 17211523) Ebana Y … Tanaka T (Journal of human genetics 2007) 3 23 41
  2. Human inter-alpha-trypsin inhibitor heavy chain H3 gene. Genomic organization, promoter analysis, and gene linkage. (PMID: 9756925) Diarra-Mehrpour M … Martin JP (The Journal of biological chemistry 1998) 3 4 23
  3. Tandem orientation of the inter-alpha-trypsin inhibitor heavy chain H1 and H3 genes. (PMID: 7522574) Diarra-Mehrpour M … Martin JP (Biochimica et biophysica acta 1994) 3 4 23
  4. Human plasma inter-alpha-trypsin inhibitor is encoded by four genes on three chromosomes. (PMID: 2465147) Diarra-Mehrpour M … Martin JP (European journal of biochemistry 1989) 2 3 4
  5. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. (PMID: 21926972) Psychiatric GWAS Consortium Bipolar Disorder Working Group (Nature genetics 2011) 3 41

Products for ITIH3 Gene

Sources for ITIH3 Gene