Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT460OO1)

• DOT Name: Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4)
• Synonyms: 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
• Gene Name: ITIH4
• Related Disease:
  Myocardial infarction
  OPTN-related open angle glaucoma
  Primary biliary cholangitis
  Rheumatoid arthritis
  Acquired immune deficiency syndrome
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Anthrax
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  Bacterial infection
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Cardiac disease
  Encephalitis
  Glioblastoma multiforme
  Glioma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  HIV-associated dementia
  Immunodeficiency
  Mental disorder
  Myelodysplastic syndrome
  Neuroblastoma
  Pulmonary tuberculosis
  Schizophrenia
  Urticaria
  Colon cancer
  Colonic neoplasm
  Familial adenomatous polyposis
  Familial adenomatous polyposis 1
  Graft-versus-host disease
  HIV infectious disease
  Neuralgia
  Non-alcoholic fatty liver disease
  Cystitis
  Dementia
  Diphtheria
  Neoplasm
  Nervous system disease
  Peripheral neuropathy
  Pneumococcal infection
• UniProt ID: ITIH4_HUMAN
• Pfam ID: PF06668 ; PF08487 ; PF00092
• Sequence:
  MKPPRPVRTCSKVLVLLSLLAIHQTTTAEKNGIDIYSLTVDSRVSSRFAHTVVTSRVVNR
  ANTVQEATFQMELPKKAFITNFSMIIDGMTYPGIIKEKAEAQAQYSAAVAKGKSAGLVKA
  TGRNMEQFQVSVSVAPNAKITFELVYEELLKRRLGVYELLLKVRPQQLVKHLQMDIHIFE
  PQGISFLETESTFMTNQLVDALTTWQNKTKAHIRFKPTLSQQQKSPEQQETVLDGNLIIR
  YDVDRAISGGSIQIENGYFVHYFAPEGLTTMPKNVVFVIDKSGSMSGRKIQQTREALIKI
  LDDLSPRDQFNLIVFSTEATQWRPSLVPASAENVNKARSFAAGIQALGGTNINDAMLMAV
  QLLDSSNQEERLPEGSVSLIILLTDGDPTVGETNPRSIQNNVREAVSGRYSLFCLGFGFD
  VSYAFLEKLALDNGGLARRIHEDSDSALQLQDFYQEVANPLLTAVTFEYPSNAVEEVTQN
  NFRLLFKGSEMVVAGKLQDRGPDVLTATVSGKLPTQNITFQTESSVAEQEAEFQSPKYIF
  HNFMERLWAYLTIQQLLEQTVSASDADQQALRNQALNLSLAYSFVTPLTSMVVTKPDDQE
  QSQVAEKPMEGESRNRNVHSGSTFFKYYLQGAKIPKPEASFSPRRGWNRQAGAAGSRMNF
  RPGVLSSRQLGLPGPPDVPDHAAYHPFRRLAILPASAPPATSNPDPAVSRVMNMKIEETT
  MTTQTPAPIQAPSAILPLPGQSVERLCVDPRHRQGPVNLLSDPEQGVEVTGQYEREKAGF
  SWIEVTFKNPLVWVHASPEHVVVTRNRRSSAYKWKETLFSVMPGLKMTMDKTGLLLLSDP
  DKVTIGLLFWDGRGEGLRLLLRDTDRFSSHVGGTLGQFYQEVLWGSPAASDDGRRTLRVQ
  GNDHSATRERRLDYQEGPPGVEISCWSVEL
• Function: Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.
• Tissue Specificity: Liver specific.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Definitive	Biomarker	[1]
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[2]
Primary biliary cholangitis	DIS43E0O	Definitive	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[4]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[5]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Amyloidosis	DISHTAI2	Strong	Biomarker	[8]
Anthrax	DISFPT78	Strong	Altered Expression	[9]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[10]
Astrocytoma	DISL3V18	Strong	Biomarker	[11]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[10]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[12]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[13]
Breast cancer	DIS7DPX1	Strong	Biomarker	[14]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[14]
Cardiac disease	DISVO1I5	Strong	Biomarker	[15]
Encephalitis	DISLD1RL	Strong	Biomarker	[16]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[17]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[20]
HIV-associated dementia	DIS8OCOC	Strong	Biomarker	[21]
Immunodeficiency	DIS093I0	Strong	Biomarker	[22]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[23]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[24]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[25]
Pulmonary tuberculosis	DIS6FLUM	Strong	Genetic Variation	[26]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[27]
Urticaria	DIS9WQAI	Strong	Biomarker	[28]
Colon cancer	DISVC52G	moderate	Biomarker	[29]
Colonic neoplasm	DISSZ04P	moderate	Biomarker	[29]
Familial adenomatous polyposis	DISW53RE	moderate	Biomarker	[29]
Familial adenomatous polyposis 1	DISM44VR	moderate	Biomarker	[29]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[30]
HIV infectious disease	DISO97HC	moderate	Genetic Variation	[31]
Neuralgia	DISWO58J	moderate	Biomarker	[32]
Non-alcoholic fatty liver disease	DISDG1NL	Disputed	Biomarker	[19]
Cystitis	DIS2D4B9	Limited	Biomarker	[33]
Dementia	DISXL1WY	Limited	Biomarker	[8]
Diphtheria	DISZWM55	Limited	Altered Expression	[34]
Neoplasm	DISZKGEW	Limited	Biomarker	[35]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[36]
Peripheral neuropathy	DIS7KN5G	Limited	Biomarker	[37]
Pneumococcal infection	DIS6SXQD	Limited	Biomarker	[38]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[42]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[43]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the phosphorylation of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4).	[45]

References

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