ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4)

Gene

• Entrez ID: 3700
• Gene name: Inter-alpha-trypsin inhibitor heavy chain 4
• Gene symbol: ITIH4
• Synonyms (NCBI Gene): GP120, H4P, IHRP, ITI-HC4, ITIHL1, PK-120, PK120
• Chromosome: 3
• Chromosome location: 3p21.1
• 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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019901	hsa-miR-375	Microarray	20215506
MIRT1074360	hsa-miR-1269	CLIP-seq
MIRT1074361	hsa-miR-1269b	CLIP-seq
MIRT1074362	hsa-miR-1288	CLIP-seq
MIRT1074363	hsa-miR-3179	CLIP-seq
MIRT1074364	hsa-miR-3646	CLIP-seq
MIRT1074365	hsa-miR-3652	CLIP-seq
MIRT1074366	hsa-miR-3662	CLIP-seq
MIRT1074367	hsa-miR-378	CLIP-seq
MIRT1074368	hsa-miR-378b	CLIP-seq
MIRT1074369	hsa-miR-378c	CLIP-seq
MIRT1074370	hsa-miR-378d	CLIP-seq
MIRT1074371	hsa-miR-378e	CLIP-seq
MIRT1074372	hsa-miR-378f	CLIP-seq
MIRT1074373	hsa-miR-378h	CLIP-seq
MIRT1074374	hsa-miR-378i	CLIP-seq
MIRT1074375	hsa-miR-422a	CLIP-seq
MIRT1074376	hsa-miR-4430	CLIP-seq
MIRT1074377	hsa-miR-4492	CLIP-seq
MIRT1074378	hsa-miR-4498	CLIP-seq
MIRT1074379	hsa-miR-4515	CLIP-seq
MIRT1074380	hsa-miR-4740-5p	CLIP-seq
MIRT1074381	hsa-miR-4766-5p	CLIP-seq
MIRT1074382	hsa-miR-762	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004866	Function	Endopeptidase inhibitor activity	TAS	9756925
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0005515	Function	Protein binding	IPI	16271702
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0006953	Process	Acute-phase response	IEA
GO:0006953	Process	Acute-phase response	IEP	19263524
GO:0030212	Process	Hyaluronan metabolic process	IEA
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0031012	Component	Extracellular matrix	HDA	25037231, 28675934
GO:0031089	Component	Platelet dense granule lumen	TAS
GO:0034097	Process	Response to cytokine	IEP	10486281
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0072562	Component	Blood microparticle	HDA	22516433

Other IDs

• MIM: 600564
• HGNC: 6169
• e!Ensembl: ENSG00000055955

Protein

• UniProt ID: Q14624
• Protein name: Inter-alpha-trypsin inhibitor heavy chain H4 (ITI heavy chain H4) (ITI-HC4) (Inter-alpha-inhibitor heavy chain 4) (Inter-alpha-trypsin inhibitor family heavy chain-related protein) (IHRP) (Plasma kallikrein sensitive glycoprotein 120) (Gp120) (PK-120) [Cl
• Protein function: Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.
• PDB: 9C4F, 9C4N
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08487	VIT	35 → 146	Vault protein inter-alpha-trypsin domain	Family
  PF00092	VWA	274 → 456	von Willebrand factor type A domain	Domain
  PF06668	ITI_HC_C	766 → 930	Inter-alpha-trypsin inhibitor heavy chain C-terminus	Family

• Tissue specificity: TISSUE SPECIFICITY: Liver specific. {ECO:0000269|PubMed:7775381, ECO:0000269|PubMed:7805892}.
• Sequence:

  MKPPRPVRTCSKVLVLLSLLAIHQTTTAEKNGIDIYSLTVDSRVSSRFAHTVVTSRVVNR
  ANTVQEATFQMELPKKAFITNFSMIIDGMTYPGIIKEKAEAQAQYSAAVAKGKSAGLVKA
  TGRNMEQFQVSVSVAPNAKITFELVYEELLKRRLGVYELLLKVRPQQLVKHLQMDIHIFE
  PQGISFLETESTFMTNQLVDALTTWQNKTKAHIRFKPTLSQQQKSPEQQETVLDGNLIIR
  YDVDRAISGGSIQIENGYFVHYFAPEGLTTMPKNVVFVIDKSGSMSGRKIQQTREALIKI
  LDDLSPRDQFNLIVFSTEATQWRPSLVPASAENVNKARSFAAGIQALGGTNINDAMLMAV
  QLLDSSNQEERLPEGSVSLIILLTDGDPTVGETNPRSIQNNVREAVSGRYSLFCLGFGFD
  VSYAFLEKLALDNGGLARRIHEDSDSALQLQDFYQEVANPLLTAVTFEYPSNAVEEVTQN
  NFRLLFKGSEMVVAGKLQDRGPDVLTATVSGKLPTQNITFQTESSVAEQEAEFQSPKYIF
  HNFMERLWAYLTIQQLLEQTVSASDADQQALRNQALNLSLAYSFVTPLTSMVVTKPDDQE
  QSQVAEKPMEGESRNRNVHSGSTFFKYYLQGAKIPKPEASFSPRRGWNRQAGAAGSRMNF
  RPGVLSSRQLGLPGPPDVPDHAAYHPFRRLAILPASAPPATSNPDPAVSRVMNMKIEETT
  MTTQTPAPIQAPSAILPLPGQSVERLCVDPRHRQGPVNLLSDPEQGVEVTGQYEREKAGF
  SWIEVTFKNPLVWVHASPEHVVVTRNRRSSAYKWKETLFSVMPGLKMTMDKTGLLLLSDP
  DKVTIGLLFWDGRGEGLRLLLRDTDRFSSHVGGTLGQFYQEVLWGSPAASDDGRRTLRVQ
  GNDHSATRERRLDYQEGPPGVEISCWSVEL

• Sequence length: 930

Pathways

Reactome:

Platelet degranulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANGINA, UNSTABLE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR I DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLONIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholesterolemia, susceptibility to	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ITIH4-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenomatous Polyposis Coli	Multiple polyposis syndrome	CTD_human_DG	25200834		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	31450610		★☆☆☆☆ Found in Text Mining only
Angina, Unstable	Intermediate coronary syndrome	BEFREE	10486281		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Arteriosclerosis	Arteriosclerosis	BEFREE	23180031		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	BEFREE	16022659, 17627037, 28978127, 8609236		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	23180031		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	21926972, 21926974, 25136889		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	21926972, 24461634, 29947131	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brain Diseases	Brain disease	Pubtator	10482626, 14691297	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	20557135		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	21048319, 21871081, 25390939, 9729531	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	31481982	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	28724284	Associate	★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	CTD_human_DG	25200834		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	31481982	Associate	★☆☆☆☆ Found in Text Mining only
Cushing's symphalangism	Proximal symphalangism	Pubtator	21612582	Associate	★☆☆☆☆ Found in Text Mining only
Cystitis	Cystitis	LHGDN	18455532		★☆☆☆☆ Found in Text Mining only
Delirium, Dementia, Amnestic, Cognitive Disorders	Delirium, Dementia, Amnestic, Cognitive Disorders	BEFREE	22575597, 25623966, 28295345, 29379089, 31238994		★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	BEFREE	16103186, 17512466, 17599380, 22575597, 28005232, 31450610		★☆☆☆☆ Found in Text Mining only
Depressed bipolar I disorder	Depressed bipolar disorder	GWASCAT_DG	31043756		★☆☆☆☆ Found in Text Mining only
Encephalitis	Encephalitis	BEFREE	24884548, 28886715, 8609236		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	11517385, 19525894, 1989385		★☆☆☆☆ Found in Text Mining only
Endometrial Hyperplasia	Endometrial hyperplasia	Pubtator	21489304	Associate	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	32106990	Associate	★☆☆☆☆ Found in Text Mining only
Familial Intestinal Polyposis	Multiple polyposis syndrome	CTD_human_DG	25200834		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	29324755		★☆☆☆☆ Found in Text Mining only
Glaucoma Open Angle	Open angle glaucoma	Pubtator	29847670	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma, Primary Open Angle	Glaucoma	BEFREE	29847670		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	16022659, 30200472		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	16022659		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	30200472		★☆☆☆☆ Found in Text Mining only
Graft-vs-Host Disease	Graft-Vs-Host Disease	BEFREE	29167672		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	31574524		★☆☆☆☆ Found in Text Mining only
Hyperalgesia	Hyperalgesia	Pubtator	35040478	Stimulate	★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	BEFREE	14661079		★☆☆☆☆ Found in Text Mining only
Hypocholesterolemia	Hypocholesterolemia	BEFREE	31757809		★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis	Pubtator	38225283	Associate	★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	15331709, 20722464	Associate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	10447929, 10630788, 10698152, 11884536, 12396109, 1384050, 16022659, 19525894, 21146610, 22696649, 2328156, 29132227, 29306566, 29936340, 8207642, 8794394, 9445013, 9621043		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	17627037, 25652249, 28128418, 31437586, 31543761, 31748578		★☆☆☆☆ Found in Text Mining only
Leprosy	Leprosy	Pubtator	29565968	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	8995603	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	10486281, 18263735, 28724284, 28828637, 31238892		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver cirrhosis	Pubtator	21590334	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	20557135		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28724284		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	CTD_human_DG	25200834		★☆☆☆☆ Found in Text Mining only
Memory dysfunction	Memory Disorders	BEFREE	28128418		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	29992445		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	30158296	Stimulate	★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood disorder	Pubtator	25136889	Associate	★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	36314970	Associate	★☆☆☆☆ Found in Text Mining only
Mycosis Fungoides	Mycosis fungoides	Pubtator	33299887	Associate	★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	20739954		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	10486281		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Necrosis	Necrosis	Pubtator	9639560	Stimulate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19997510, 22484292		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	15307952, 31748578		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	10820198, 16001969, 18973553, 28392757, 9520163		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	10820198, 16877302	Associate	★☆☆☆☆ Found in Text Mining only
Neurocognitive Disorders	Neurocognitive Disorders	BEFREE	22575597, 25623966, 28295345, 29379089, 31238994		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	29147885	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30280668		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	31320730, 31379513		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	31238892		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	26449484	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	28683725	Associate	★☆☆☆☆ Found in Text Mining only
Pediatric Obesity	Childhood obesity	BEFREE	29769702		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	30933958, 31748578		★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	30933958, 31748578		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	30946770	Associate	★☆☆☆☆ Found in Text Mining only
Polyposis, Adenomatous Intestinal	Multiple polyposis syndrome	CTD_human_DG	25200834		★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	16103186, 17512466, 17599380, 28005232, 31450610		★☆☆☆☆ Found in Text Mining only
Primary biliary cirrhosis	Biliary Cirrhosis	BEFREE	31737133		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	24505114	Associate	★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychotic disorders	Pubtator	24461634	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	25977605	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	29636082		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	21926972, 29136250, 29947131, 30195780		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	21926972, 21926974, 22614287, 24461634, 25136889, 29947131	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASDB_DG	21926974		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASCAT_DG	21926974		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs Inversus	Situs Inversus	BEFREE	10684319, 18832708, 28366604, 29523166, 30153309		★☆☆☆☆ Found in Text Mining only
Skin lesion	Skin Lesion	BEFREE	12388730		★☆☆☆☆ Found in Text Mining only
Sleep Deprivation	Sleep deprivation	Pubtator	30158296	Stimulate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	25952687	Stimulate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34687700	Associate	★☆☆☆☆ Found in Text Mining only
Tetany	Tetany	Pubtator	8495981	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	38216619	Associate	★☆☆☆☆ Found in Text Mining only
Urticaria	Urticaria	BEFREE	10482626, 26936603		★☆☆☆☆ Found in Text Mining only
Vesicular Stomatitis	Vesicular Stomatitis	BEFREE	12551992		★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin d deficiency	Pubtator	23877860	Associate	★☆☆☆☆ Found in Text Mining only
X-linked agammaglobulinemia	Agammaglobulinemia, X-Linked	BEFREE	11857356		★☆☆☆☆ Found in Text Mining only