Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKBS8CC)

• DOT Name: Proton-activated chloride channel (PACC1)
• Synonyms: PAC; hPAC; Acid-sensitive outwardly-rectifying anion channel; ASOR; Proton-activated outwardly rectifying anion channel; PAORAC; Transmembrane protein 206; hTMEM206
• Gene Name: PACC1
• Related Disease:
  Neuroblastoma
  Pancreatic adenocarcinoma
  Pancreatic cancer
  Acute otitis media
  Adenocarcinoma
  Advanced cancer
  Angle-closure glaucoma
  Autosomal dominant optic atrophy, classic form
  Bipolar disorder
  Bone osteosarcoma
  Breast carcinoma
  Cataract
  Clear cell renal carcinoma
  Colorectal carcinoma
  Constipation
  Familial Mediterranean fever
  Fatty liver disease
  Germ cell tumor
  Irritable bowel syndrome
  Leukemia
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Medulloblastoma
  Myopathy
  Neoplasm
  Neurofibromatosis type 1
  Osteosarcoma
  Otitis media
  Primary angle-closure glaucoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Rhabdomyosarcoma
  Severe combined immunodeficiency
  Small lymphocytic lymphoma
  Smith-Magenis syndrome
  Thyroid tumor
  Urinary tract infection
  Uterine fibroids
  Chronic obstructive pulmonary disease
  Female hypogonadism
  Influenza
  Arrhythmia
  Atopic dermatitis
  Venous thromboembolism
• UniProt ID: PACC1_HUMAN
• PDB ID: 7JNA; 7JNC; 7SQF; 7SQG; 7SQH; 8EQ4; 8FBL
• Pfam ID: PF15122
• Sequence:
  MIRQERSTSYQELSEELVQVVENSELADEQDKETVRVQGPGILPGLDSESASSSIRFSKA
  CLKNVFSVLLIFIYLLLMAVAVFLVYRTITDFREKLKHPVMSVSYKEVDRYDAPGIALYP
  GQAQLLSCKHHYEVIPPLTSPGQPGDMNCTTQRINYTDPFSNQTVKSALIVQGPREVKKR
  ELVFLQFRLNKSSEDFSAIDYLLFSSFQEFLQSPNRVGFMQACESAYSSWKFSGGFRTWV
  KMSLVKTKEEDGREAVEFRQETSVVNYIDQRPAAKKSAQLFFVVFEWKDPFIQKVQDIVT
  ANPWNTIALLCGAFLALFKAAEFAKLSIKWMIKIRKRYLKRRGQATSHIS
• Function: Chloride channel gated by pH that facilitates the entry of chloride ions into cells upon exposure to extracellular acidic pH. Involved in acidosis-induced cell death by mediating chloride influx and subsequent cell swelling.
• Tissue Specificity: Widely expressed, with highest expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Pancreatic adenocarcinoma	DISKHX7S	Definitive	Biomarker	[2]
Pancreatic cancer	DISJC981	Definitive	Genetic Variation	[3]
Acute otitis media	DISL8D8G	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[6]
Angle-closure glaucoma	DISZ95KY	Strong	Genetic Variation	[7]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Genetic Variation	[8]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[9]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[11]
Cataract	DISUD7SL	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Constipation	DISRQXWI	Strong	Biomarker	[13]
Familial Mediterranean fever	DISVP5WP	Strong	Biomarker	[14]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[15]
Germ cell tumor	DIS62070	Strong	Genetic Variation	[16]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[13]
Leukemia	DISNAKFL	Strong	Biomarker	[17]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[18]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[2]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[19]
Myopathy	DISOWG27	Strong	Genetic Variation	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Neurofibromatosis type 1	DIS53JH9	Strong	Genetic Variation	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[10]
Otitis media	DISGZDUO	Strong	Biomarker	[4]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Genetic Variation	[7]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[24]
Rhabdomyosarcoma	DISNR7MS	Strong	Biomarker	[25]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[26]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[27]
Smith-Magenis syndrome	DISG4G6X	Strong	Biomarker	[28]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[29]
Urinary tract infection	DISMT6UV	Strong	Biomarker	[30]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[31]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[32]
Female hypogonadism	DISWASB4	moderate	Biomarker	[33]
Influenza	DIS3PNU3	moderate	Biomarker	[34]
Arrhythmia	DISFF2NI	Limited	Genetic Variation	[35]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[36]
Venous thromboembolism	DISUR7CR	Limited	Biomarker	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Proton-activated chloride channel (PACC1).	[38]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Proton-activated chloride channel (PACC1).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Proton-activated chloride channel (PACC1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Proton-activated chloride channel (PACC1).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proton-activated chloride channel (PACC1).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proton-activated chloride channel (PACC1).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Proton-activated chloride channel (PACC1).	[42]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Proton-activated chloride channel (PACC1).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Proton-activated chloride channel (PACC1).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Proton-activated chloride channel (PACC1).	[46]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Proton-activated chloride channel (PACC1).	[48]

References

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