ITIH4

inter-alpha-trypsin inhibitor heavy chain 4, the group of Inter-alpha-trypsin inhibitor heavy chains

Basic information

Region (hg38): 3:52812961-52830688

Previous symbols: [ "ITIHL1" ]

Links

ENSG00000055955 ∙ NCBI:3700 ∙ OMIM:600564 ∙ HGNC:6169 ∙ Uniprot:Q14624 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITIH4 gene.

• Inborn genetic diseases (35 variants)
• not provided (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITIH4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	5	6
missense			30	6	2	38
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	30	7	7

Variants in ITIH4

This is a list of pathogenic ClinVar variants found in the ITIH4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-52813453-C-T		not specified	Uncertain significance (Jan 03, 2022)
3-52813464-C-G		not specified	Uncertain significance (Nov 21, 2023)
3-52813968-A-G		ITIH4-related disorder	Benign (Nov 06, 2019)
3-52814021-C-T			Benign (Jun 06, 2018)
3-52814224-C-T		not specified	Uncertain significance (Sep 01, 2021)
3-52814250-C-T		not specified	Uncertain significance (Sep 14, 2021)
3-52814251-G-C		not specified	Uncertain significance (Jan 10, 2022)
3-52814262-C-T		not specified	Uncertain significance (Mar 13, 2023)
3-52814277-C-A		not specified	Uncertain significance (Feb 26, 2024)
3-52814277-C-T		not specified	Uncertain significance (Sep 20, 2023)
3-52814278-G-A		not specified	Uncertain significance (Oct 03, 2022)
3-52814287-A-G		not specified	Uncertain significance (Jun 12, 2023)
3-52814338-C-T		not specified	Uncertain significance (Nov 22, 2023)
3-52816939-T-G		not specified	Uncertain significance (Feb 14, 2023)
3-52816957-G-T		not specified	Uncertain significance (Sep 14, 2022)
3-52816983-A-G		ITIH4-related disorder	Benign (Nov 06, 2019)
3-52818044-T-C		ITIH4-related disorder	Benign (Oct 17, 2019)
3-52818085-C-A		not specified	Uncertain significance (Jul 26, 2022)
3-52818091-G-A		not specified	Uncertain significance (Nov 13, 2023)
3-52818114-C-T		not specified	Likely benign (Dec 15, 2023)
3-52818122-A-G		ITIH4-related disorder	Benign (Nov 06, 2019)
3-52818126-T-A		not specified	Uncertain significance (Nov 10, 2022)
3-52818164-G-A		ITIH4-related disorder	Benign/Likely benign (Nov 26, 2019)
3-52818171-G-A			Benign (May 30, 2018)
3-52818465-C-T		not specified	Likely benign (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITIH4	protein_coding	protein_coding	ENST00000266041	24	18505

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.44e-13	0.998	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	478	563	0.849	0.0000337	6042
Missense in Polyphen		157	208.31	0.75369		2455
Synonymous	0.263	223	228	0.978	0.0000140	1871
Loss of Function	2.88	28	50.0	0.560	0.00000247	542

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00104	0.00104
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000602	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.000311	0.000308
Middle Eastern	0.000602	0.000435
South Asian	0.000639	0.000457
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration. {ECO:0000269|PubMed:19263524}.
• Pathway: Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.306

Intolerance Scores

• loftool: 0.772
• rvis_EVS: -0.43
• rvis_percentile_EVS: 24.72

Haploinsufficiency Scores

• pHI: 0.330
• hipred: N
• hipred_score: 0.370
• ghis: 0.402

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itih4
• Phenotype: cellular phenotype; neoplasm; normal phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: platelet degranulation;acute-phase response;negative regulation of endopeptidase activity;hyaluronan metabolic process;response to cytokine
• Cellular component: extracellular region;plasma membrane;platelet dense granule lumen;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;protein binding