ITIH6

protein-coding

inter-alpha-trypsin inhibitor heavy chain family member 6, the group of Inter-alpha-trypsin inhibitor heavy chains

Gene summary

The protein encoded by this gene belongs to the interalpha trypsin inhibitor heavy chain (ITIH) family. Interalpha trypsin inhibitor (ITI) is composed of two heavy chains (containing VWA domain) and one light chain. The light chain confers the protease-inhibitor function, while the heavy chains are involved in mediating protein-protein interactions with the components of the extracellular matrix. [provided by RefSeq, Sep 2009]

Previous symbols:

ITIH5L

MANE transcript

NM_198510.3

Inheritance

—

ClinVar variants

P:1U:236B:22

Top phenotype

ITIH6-related disorder

gnomAD constraint

pLI —, LoF o/e 1.14

Max pathogenic AF

—

Genomic locus

chrX:54,748,918-54,798,255

External References & Databases

Ensembl (ENSG00000102313)

Transcript & Mutation Effects

hg38 • Region Span ~49.3 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 ITIH6 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 215

ITIH6-related disorderTotal: 17

not providedTotal: 9

Short statureTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198510.3. 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			2 clinvar	4 clinvar		6
missense			226 clinvar	14 clinvar	2 clinvar	242
nonsense	1 clinvar		4 clinvar	1 clinvar		6
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar	1 clinvar		4
Total	1	0	236	20	2	259

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198510.3	RefSeq	NP_940912.1	13	MANE Select
ENST00000218436.7	Ensembl	ENSP00000218436.6	13	MANE Select

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

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000218436
Coding exons: 13
Length: 49342
Individuals with no LoFs: 125643
Homozygous LoFs: 35
Heterozygous LoFs: 69
Defined: 125747
p: 0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.30	648	503	1.29	0.0000387	8398
Missense (PolyPhen)		100	93.942	1.0645		1886
Synonymous	-1.71	238	207	1.15	0.0000156	2898
Loss of Function	-0.711	34	29.8	1.14	0.00000232	513

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0048	0.0039	notable
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00016	rare
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.00036	0.00025	rare
South Asian	0.00022	0.00013	rare
Other	0.00045	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: 2.57
RVIS percentile EVS: 98.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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