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Aliases for ITIH2 Gene

Aliases for ITIH2 Gene

  • Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 2 3 5
  • Inter-Alpha-Trypsin Inhibitor Complex Component II 3 4
  • Inter-Alpha (Globulin) Inhibitor, H2 Polypeptide 2 3
  • Serum-Derived Hyaluronan-Associated Protein 3 4
  • Inter-Alpha-Inhibitor Heavy Chain 2 3 4
  • ITI Heavy Chain H2 3 4
  • ITI-HC2 3 4
  • SHAP 3 4
  • Inter-Alpha-Trypsin Inhibitor Heavy Chain H2 3
  • Inter-Alpha (Globulin) Inhibitor H2 3
  • IGHEP2 4
  • H2P 3

External Ids for ITIH2 Gene

Previous GeneCards Identifiers for ITIH2 Gene

  • GC10P007689
  • GC10P007895
  • GC10P007749
  • GC10P007785

Summaries for ITIH2 Gene

Entrez Gene Summary for ITIH2 Gene

  • The inter-alpha-trypsin inhibitors (ITI) are a family of structurally related plasma serine protease inhibitors involved in extracellular matrix stabilization and in prevention of tumor metastasis. The ITI family contains multiple proteins made up of a light chain (see MIM 176870) and a variable number of heavy chains (Salier et al., 1987 [PubMed 2446322]; Himmelfarb et al., 2004 [PubMed 14744536]).[supplied by OMIM, Nov 2009]

GeneCards Summary for ITIH2 Gene

ITIH2 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 2) is a Protein Coding gene. Diseases associated with ITIH2 include Background Diabetic Retinopathy. Among its related pathways are 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 ITIH3.

UniProtKB/Swiss-Prot for ITIH2 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 ITIH2 Gene

Additional gene information for ITIH2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ITIH2 Gene

Genomics for ITIH2 Gene

GeneHancer (GH) Regulatory Elements for ITIH2 Gene

Promoters and enhancers for ITIH2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J007703 Promoter 1.1 EPDnew 650.7 +0.1 69 0.1 FOXA2 ARID4B RARA YY1 EGR1 CREM MIXL1 SP5 REST PPARG ITIH2 GC10P007710
GH10J007701 Enhancer 0.4 FANTOM5 650.7 -1.7 -1726 0.1 SP1 HNF4G HNF4A ITIH2 ITIH5
GH10J007786 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 7 +85.5 85527 4.2 HDGF PKNOX1 SMAD1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 POLR2B KIN ATP5F1C ITIH2 GC10M007790
GH10J007796 Enhancer 0.8 Ensembl ENCODE 16.9 +94.7 94654 2.3 SMARCE1 JUN DPF2 ZNF148 FOSL1 JUND EGR1 SMARCA4 VEZF1 ZBTB33 GC10M007790 ITIH2 ATP5F1C PIR42243 GC10P007806
GH10J007794 Enhancer 0.8 ENCODE 13.6 +92.4 92351 1.8 FOXA2 ARID4B DMAP1 ZNF614 ZSCAN5C THAP11 SP5 MXD4 KAT8 MIER3 GC10M007790 ITIH2 ATP5F1C
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ITIH2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ITIH2 gene promoter:
  • PPAR-gamma2
  • PPAR-gamma1
  • RSRFC4
  • MZF-1
  • MyoD
  • FOXJ2
  • FOXJ2 (long isoform)
  • Olf-1
  • STAT5A
  • HFH-3

Genomic Locations for ITIH2 Gene

Genomic Locations for ITIH2 Gene
46,252 bases
Plus strand
46,252 bases
Plus strand

Genomic View for ITIH2 Gene

Genes around ITIH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ITIH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ITIH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ITIH2 Gene

Proteins for ITIH2 Gene

  • Protein details for ITIH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Inter-alpha-trypsin inhibitor heavy chain H2
    Protein Accession:
    Secondary Accessions:
    • Q14659
    • Q15484
    • Q5T986

    Protein attributes for ITIH2 Gene

    946 amino acids
    Molecular mass:
    106463 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.
    • Sequence=CAA30160.1; Type=Frameshift; Positions=363, 373; Evidence={ECO:0000305};

neXtProt entry for ITIH2 Gene

Post-translational modifications for ITIH2 Gene

  • Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.
  • N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.
  • Phosphorylated by FAM20C in the extracellular medium.
  • Glycosylation at Thr691, Thr675, isoforms=673, isoforms=666, Thr601, Asn445, Asn118, and isoforms=96
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ITIH2_HUMAN (285)

Other Protein References for ITIH2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ITIH2 Gene

Domains & Families for ITIH2 Gene

Gene Families for ITIH2 Gene

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

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the ITIH family.
  • Belongs to the ITIH family.
genes like me logo Genes that share domains with ITIH2: view

Function for ITIH2 Gene

Molecular function for ITIH2 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 2

Phenotypes From GWAS Catalog for ITIH2 Gene

Gene Ontology (GO) - Molecular Function for ITIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity TAS 2476436
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with ITIH2: view
genes like me logo Genes that share phenotypes with ITIH2: view

Animal Model Products

  • Taconic Biosciences Mouse Models for ITIH2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for ITIH2 Gene

Localization for ITIH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ITIH2 Gene


Subcellular locations from

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 ITIH2 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
golgi apparatus 2
mitochondrion 1
peroxisome 1
nucleus 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ITIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region NAS 14718574
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0070062 extracellular exosome HDA 20458337
GO:0072562 blood microparticle HDA 22516433
genes like me logo Genes that share ontologies with ITIH2: view

Pathways & Interactions for ITIH2 Gene

genes like me logo Genes that share pathways with ITIH2: view

Pathways by source for ITIH2 Gene

1 GeneGo (Thomson Reuters) pathway for ITIH2 Gene

Gene Ontology (GO) - Biological Process for ITIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0030212 hyaluronan metabolic process IEA --
GO:0043687 post-translational protein modification TAS --
GO:0044267 cellular protein metabolic process TAS --
genes like me logo Genes that share ontologies with ITIH2: view

No data available for SIGNOR curated interactions for ITIH2 Gene

Drugs & Compounds for ITIH2 Gene

(2) Drugs for ITIH2 Gene - From: DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma Target 202
Zinc Approved, Investigational Pharma Target 2430
genes like me logo Genes that share compounds with ITIH2: view

Transcripts for ITIH2 Gene

mRNA/cDNA for ITIH2 Gene

(1) REFSEQ mRNAs :
(8) Additional mRNA sequences :
(133) Selected AceView cDNA sequences:
(6) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for ITIH2 Gene

Inter-alpha-trypsin inhibitor heavy chain 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ITIH2 Gene

No ASD Table

Relevant External Links for ITIH2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for ITIH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ITIH2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ITIH2 Gene

This gene is overexpressed in Liver (x50.2).

Protein differential expression in normal tissues from HIPED for ITIH2 Gene

This gene is overexpressed in Serum (27.4), Plasma (13.2), and Synovial fluid (9.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ITIH2 Gene

Protein tissue co-expression partners for ITIH2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ITIH2 Gene:


SOURCE GeneReport for Unigene cluster for ITIH2 Gene:


mRNA Expression by UniProt/SwissProt for ITIH2 Gene:

Tissue specificity: Plasma.

Evidence on tissue expression from TISSUES for ITIH2 Gene

  • Liver(4.9)
  • Bone marrow(4)
genes like me logo Genes that share expression patterns with ITIH2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ITIH2 Gene

Orthologs for ITIH2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ITIH2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ITIH2 34
  • 96 (a)
(Canis familiaris)
Mammalia ITIH2 34 33
  • 85.2 (n)
(Bos Taurus)
Mammalia ITIH2 34 33
  • 85.13 (n)
(Mus musculus)
Mammalia Itih2 16 34 33
  • 82.52 (n)
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 82 (a)
-- 34
  • 78 (a)
-- 34
  • 73 (a)
(Monodelphis domestica)
Mammalia ITIH2 34
  • 75 (a)
(Gallus gallus)
Aves ITIH2 34 33
  • 68.97 (n)
(Anolis carolinensis)
Reptilia ITIH2 34
  • 61 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia itih2 33
  • 63.13 (n)
Str.15358 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.5099 33
(Danio rerio)
Actinopterygii itih2 34
  • 52 (a)
Dr.852 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2708 33
Species where no ortholog for ITIH2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ITIH2 Gene

Gene Tree for ITIH2 (if available)
Gene Tree for ITIH2 (if available)
Evolutionary constrained regions (ECRs) for ITIH2: view image

Paralogs for ITIH2 Gene

Paralogs for ITIH2 Gene

(5) SIMAP similar genes for ITIH2 Gene using alignment to 5 proteins:

  • Q5T985_HUMAN
  • Q5T987_HUMAN
genes like me logo Genes that share paralogs with ITIH2: view

Variants for ITIH2 Gene

Sequence variations from dbSNP and Humsavar for ITIH2 Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1000061762 -- 7,702,401(+) T/A upstream_transcript_variant
rs1000098543 -- 7,741,635(+) C/G intron_variant
rs1000176705 -- 7,719,455(+) T/C intron_variant
rs1000206468 -- 7,719,738(+) A/G intron_variant
rs1000230112 -- 7,723,449(+) A/C splice_acceptor_variant

Structural Variations from Database of Genomic Variants (DGV) for ITIH2 Gene

Variant ID Type Subtype PubMed ID
esv1496692 CNV insertion 17803354
esv1652715 CNV deletion 17803354
esv2606150 CNV deletion 19546169
esv2670009 CNV deletion 23128226
esv2732373 CNV deletion 23290073
esv2732384 CNV deletion 23290073
esv3622276 CNV loss 21293372
esv3891752 CNV gain 25118596
nsv1038131 CNV gain 25217958
nsv1069015 CNV deletion 25765185
nsv549933 CNV gain 21841781
nsv957606 CNV deletion 24416366

Variation tolerance for ITIH2 Gene

Residual Variation Intolerance Score: 63.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.01; 74.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ITIH2 Gene

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

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ITIH2 Gene

Disorders for ITIH2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for ITIH2 Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
background diabetic retinopathy
  • non proliferative diabetic retinopathy
- elite association - COSMIC cancer census association via MalaCards
Search ITIH2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ITIH2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ITIH2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ITIH2 Gene

Publications for ITIH2 Gene

  1. A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor. (PMID: 7504674) Huang L … Kimata K (The Journal of biological chemistry 1993) 3 4 22 58
  2. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. (PMID: 16385451) Grupe A … Goate A (American journal of human genetics 2006) 3 44 58
  3. SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. (PMID: 16702221) Zhuo L … Kimata K (The Journal of biological chemistry 2006) 3 22 58
  4. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. (PMID: 16335952) Liu T … Smith RD (Journal of proteome research 2005) 3 4 58
  5. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. (PMID: 12754519) Zhang H … Aebersold R (Nature biotechnology 2003) 3 4 58

Products for ITIH2 Gene

Sources for ITIH2 Gene

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