ITIH2

protein-coding

inter-alpha-trypsin inhibitor heavy chain 2, the group of Inter-alpha-trypsin inhibitor heavy chains|Gla domain containing

Gene summary

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]

MANE transcript

NM_002216.3

Inheritance

—

ClinVar variants

U:145B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr10:7,703,316-7,749,520

External References & Databases

Ensembl (ENSG00000151655)

Transcript & Mutation Effects

hg38 • Region Span ~46.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITIH2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 142

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002216.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			144 clinvar	2 clinvar		146
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	145	3	0	148

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002216.3	RefSeq	NP_002207.2	21	MANE Select
ENST00000358415.9	Ensembl	ENSP00000351190.4	21	MANE Select
ENST00000379587.4	Ensembl	ENSP00000368906.3	20	Standard
ENST00000379587.5	Ensembl	ENSP00000368906.3	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein phosphorylation
Post-translational protein modification
Metabolism of proteins
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Biological Process

negative regulation of endopeptidase activity
hyaluronan metabolic process
post-translational protein modification
cellular protein metabolic process

Molecular Function

endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity

Cellular Component

extracellular region
endoplasmic reticulum lumen
collagen-containing extracellular matrix
extracellular exosome
blood microparticle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358415
Coding exons: 21
Length: 46252
Individuals with no LoFs: 125363
Homozygous LoFs: 2
Heterozygous LoFs: 382
Defined: 125747
p: 0.00153

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.613	495	535	0.925	0.0000296	6237
Missense (PolyPhen)		159	168.65	0.94281		2038
Synonymous	0.337	209	215	0.971	0.0000138	1797
Loss of Function	1.04	39	46.6	0.836	0.00000223	570

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00077	0.00075	rare
Ashkenazi Jewish	0.0022	0.0022	notable
East Asian	0.0016	0.0016	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0051	0.0050	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.557
RVIS EVS: 0.15
RVIS percentile EVS: 63.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.835

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium