ITIH5

protein-coding

inter-alpha-trypsin inhibitor heavy chain 5, the group of Inter-alpha-trypsin inhibitor heavy chains

Gene summary

This gene encodes a heavy chain component of one of the inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins are involved in extracellular matrix stabilization and in the prevention of tumor metastasis. They are also structurally related plasma serine protease inhibitors and are composed of a light chain and varying numbers of heavy chains. This family member is thought to function as a tumor suppressor in breast and thyroid cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

MANE transcript

NM_030569.7

Inheritance

—

ClinVar variants

U:155B:17

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr10:7,559,270-7,666,998

External References & Databases

Ensembl (ENSG00000123243)

Transcript & Mutation Effects

hg38 • Region Span ~107.7 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 ITIH5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 158

not providedTotal: 4

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030569.7. 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	2 clinvar	3
missense			150 clinvar	14 clinvar		164
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	155	15	2	172

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030569.7	RefSeq	NP_085046.5	14	MANE Select
ENST00000397146.7	Ensembl	ENSP00000380333.3	14	MANE Select
NM_001001851.3	RefSeq	NP_001001851.1	12	Standard
NM_032817.6	RefSeq	NP_116206.4	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of endopeptidase activity
hyaluronan metabolic process

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256861
Coding exons: 14
Length: 107730
Individuals with no LoFs: 125573
Homozygous LoFs: 0
Heterozygous LoFs: 175
Defined: 125748
p: 0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.136	559	568	0.984	0.0000337	6234
Missense (PolyPhen)		193	197.98	0.97483		2268
Synonymous	-1.99	285	245	1.16	0.0000168	1938
Loss of Function	0.528	33	36.4	0.906	0.00000198	406

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0011	notable
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00060	0.00060	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00095	0.00093	rare
South Asian	0.00070	0.00069	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a tumor suppressor.;

Recessive Scores

pRec: 0.111

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

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