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

Summary

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

Location:: 3p21.1

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (52812962..52830672, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (52845872..52863582, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (52846978..52864688, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.
Title: ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.
ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.
Title: ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.
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.
sgp120 or ITIH4 is cleaved when the contact system is activated and this cleavage could be used as a biomarker in patients with hereditary angioedema with normal C1 inhibitor
Title: sgp120 and the contact system in hereditary angioedema: A diagnostic tool in HAE with normal C1 inhibitor.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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 EBI GWAS CatalogPubMed
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies five new schizophrenia loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

PMC117798P1 (e-PCR)
- UniSTS:270349

PMC117798P10 (e-PCR)
- UniSTS:270350

PMC117798P11 (e-PCR)
- UniSTS:270351

PMC117798P12 (e-PCR)
- UniSTS:270352

PMC117798P13 (e-PCR)
- UniSTS:270353

PMC117798P14 (e-PCR)
- UniSTS:270354

PMC117798P15 (e-PCR)
- UniSTS:270355

PMC117798P16 (e-PCR)
- UniSTS:270356

PMC117798P17 (e-PCR)
- UniSTS:270357

PMC117798P18 (e-PCR)
- UniSTS:270358

PMC117798P19 (e-PCR)
- UniSTS:270359

PMC117798P2 (e-PCR)
- UniSTS:270360

PMC117798P20 (e-PCR)
- UniSTS:270361

PMC117798P21 (e-PCR)
- UniSTS:270362

PMC117798P22 (e-PCR)
- UniSTS:270363

PMC117798P23 (e-PCR)
- UniSTS:270364

PMC117798P24 (e-PCR)
- UniSTS:270365

PMC117798P25 (e-PCR)
- UniSTS:270366

PMC117798P3 (e-PCR)
- UniSTS:270367

PMC117798P4 (e-PCR)
- UniSTS:270368

PMC117798P5 (e-PCR)
- UniSTS:270369

PMC117798P6 (e-PCR)
- UniSTS:270370

PMC117798P7 (e-PCR)
- UniSTS:270371

PMC117798P8 (e-PCR)
- UniSTS:270372

PMC117798P9 (e-PCR)
- UniSTS:270373

SHGC-53936 (e-PCR)
- UniSTS:65384

A005P36 (e-PCR)
- UniSTS:21705

A008L08 (e-PCR)
- UniSTS:52175

SHGC-84788 (e-PCR)
- UniSTS:104162

RH93187 (e-PCR)
- UniSTS:87268

RH36516 (e-PCR)
- UniSTS:62449

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 response to cytokine	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	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

NG_016006.2 RefSeqGene

Range

5030..22740

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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