Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT94MKL)

• DOT Name: Gap junction alpha-1 protein (GJA1)
• Synonyms: Connexin-43; Cx43; Gap junction 43 kDa heart protein
• Gene Name: GJA1
• Related Disease:
  Hypoplastic left heart syndrome 1
  Oculodentodigital dysplasia
  Oculodentodigital dysplasia, autosomal recessive
  Autosomal dominant palmoplantar keratoderma and congenital alopecia
  Erythrokeratodermia variabilis et progressiva 3
  Craniometaphyseal dysplasia
  Erythrokeratodermia variabilis
  Syndactyly type 3
  Nonsyndromic genetic hearing loss
  Craniometaphyseal dysplasia, autosomal recessive
  Hallermann-Streiff syndrome
• UniProt ID: CXA1_HUMAN
• PDB ID: 2LL2; 7F92; 7F93; 7F94; 7XQ9; 7XQB; 7XQD; 7XQF; 7XQG; 7XQH; 7XQI; 7XQJ; 7Z1T; 7Z22; 7Z23
• Pfam ID: PF00029 ; PF03508
• Sequence:
  MGDWSALGKLLDKVQAYSTAGGKVWLSVLFIFRILLLGTAVESAWGDEQSAFRCNTQQPG
  CENVCYDKSFPISHVRFWVLQIIFVSVPTLLYLAHVFYVMRKEEKLNKKEEELKVAQTDG
  VNVDMHLKQIEIKKFKYGIEEHGKVKMRGGLLRTYIISILFKSIFEVAFLLIQWYIYGFS
  LSAVYTCKRDPCPHQVDCFLSRPTEKTIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRV
  KGKSDPYHATSGALSPAKDCGSQKYAYFNGCSSPTAPLSPMSPPGYKLVTGDRNNSSCRN
  YNKQASEQNWANYSAEQNRMGQAGSTISNSHAQPFDFPDDNQNSKKLAAGHELQPLAIVD
  QRPSSRASSRASSRPRPDDLEI
• Function: Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract. May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles.
• Tissue Specificity: Expressed in the heart and fetal cochlea.
• KEGG Pathway:
  Gap junction (hsa04540)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
• Reactome Pathway:
  Transport of connexins along the secretory pathway (R-HSA-190827)
  Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane (R-HSA-190840)
  Gap junction assembly (R-HSA-190861)
  Gap junction degradation (R-HSA-190873)
  Regulation of gap junction activity (R-HSA-191650)
  Formation of annular gap junctions (R-HSA-196025)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOJ GTPase cycle (R-HSA-9013409)
  SARS-CoV-2 targets PDZ proteins in cell-cell junction (R-HSA-9705677)
  Oligomerization of connexins into connexons (R-HSA-190704)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypoplastic left heart syndrome 1	DISW3OY8	Definitive	Autosomal dominant	[1]
Oculodentodigital dysplasia	DISSWR9C	Definitive	Semidominant	[2]
Oculodentodigital dysplasia, autosomal recessive	DISAAEON	Definitive	Autosomal recessive	[3]
Autosomal dominant palmoplantar keratoderma and congenital alopecia	DISQI2AI	Strong	Autosomal dominant	[4]
Erythrokeratodermia variabilis et progressiva 3	DIS8JGKH	Strong	Autosomal dominant	[4]
Craniometaphyseal dysplasia	DISK6EZQ	Supportive	Autosomal dominant	[5]
Erythrokeratodermia variabilis	DIS4BMUQ	Supportive	Autosomal dominant	[6]
Syndactyly type 3	DISDD010	Supportive	Autosomal dominant	[3]
Nonsyndromic genetic hearing loss	DISZX61P	Disputed	Autosomal dominant	[7]
Craniometaphyseal dysplasia, autosomal recessive	DISXHFIL	Limited	Autosomal recessive	[2]
Hallermann-Streiff syndrome	DISNT5DL	Limited	Autosomal recessive	[8]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Gap junction alpha-1 protein (GJA1) affects the response to substance of Fluorouracil.	[44]
Topotecan	DMP6G8T	Approved	Gap junction alpha-1 protein (GJA1) affects the response to substance of Topotecan.	[44]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Adenosine triphosphate	DM79F6G	Approved	Gap junction alpha-1 protein (GJA1) increases the export of Adenosine triphosphate.	[45]

37 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 Gap junction alpha-1 protein (GJA1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Gap junction alpha-1 protein (GJA1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Gap junction alpha-1 protein (GJA1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Gap junction alpha-1 protein (GJA1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Gap junction alpha-1 protein (GJA1).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Gap junction alpha-1 protein (GJA1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Gap junction alpha-1 protein (GJA1).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Gap junction alpha-1 protein (GJA1).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Gap junction alpha-1 protein (GJA1).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Gap junction alpha-1 protein (GJA1).	[19]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Gap junction alpha-1 protein (GJA1).	[20]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Gap junction alpha-1 protein (GJA1).	[21]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Gap junction alpha-1 protein (GJA1).	[22]
Irinotecan	DMP6SC2	Approved	Irinotecan affects the expression of Gap junction alpha-1 protein (GJA1).	[23]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Gap junction alpha-1 protein (GJA1).	[24]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Gap junction alpha-1 protein (GJA1).	[25]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Gap junction alpha-1 protein (GJA1).	[26]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Gap junction alpha-1 protein (GJA1).	[27]
Flutamide	DMK0O7U	Approved	Flutamide decreases the expression of Gap junction alpha-1 protein (GJA1).	[28]
Carvedilol	DMHTEAO	Approved	Carvedilol increases the expression of Gap junction alpha-1 protein (GJA1).	[29]
Letrozole	DMH07Y3	Approved	Letrozole decreases the expression of Gap junction alpha-1 protein (GJA1).	[21]
Griseofulvin	DMK54YG	Approved	Griseofulvin increases the expression of Gap junction alpha-1 protein (GJA1).	[30]
Anastrozole	DMNP60F	Approved	Anastrozole decreases the expression of Gap junction alpha-1 protein (GJA1).	[21]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Gap junction alpha-1 protein (GJA1).	[21]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Gap junction alpha-1 protein (GJA1).	[25]
Fucoxanthin	DMPQFTA	Phase 2	Fucoxanthin increases the expression of Gap junction alpha-1 protein (GJA1).	[31]
G1	DMTV42K	Phase 1/2	G1 decreases the expression of Gap junction alpha-1 protein (GJA1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Gap junction alpha-1 protein (GJA1).	[33]
Calphostin C	DM9X2D0	Terminated	Calphostin C affects the expression of Gap junction alpha-1 protein (GJA1).	[34]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Gap junction alpha-1 protein (GJA1).	[36]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Gap junction alpha-1 protein (GJA1).	[38]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of Gap junction alpha-1 protein (GJA1).	[39]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Gap junction alpha-1 protein (GJA1).	[40]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Gap junction alpha-1 protein (GJA1).	[41]
Bafilomycin A1	DMUNK59	Investigative	Bafilomycin A1 increases the expression of Gap junction alpha-1 protein (GJA1).	[40]
toxaphene	DM4R657	Investigative	toxaphene decreases the expression of Gap junction alpha-1 protein (GJA1).	[42]
norfluoxetine	DMKNUP3	Investigative	norfluoxetine increases the expression of Gap junction alpha-1 protein (GJA1).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Gap junction alpha-1 protein (GJA1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gap junction alpha-1 protein (GJA1).	[35]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the phosphorylation of Gap junction alpha-1 protein (GJA1).	[37]

References

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