Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL0TRR5)

DOT Name	Calcium-binding protein 4 (CABP4)
Synonyms	CaBP4
Gene Name	CABP4
Related Disease	Cone-rod synaptic disorder, congenital nonprogressive ( ) Congenital stationary night blindness 2A ( ) Myopia ( ) Night blindness ( ) Leber congenital amaurosis ( ) Leber congenital amaurosis 1 ( ) Retinopathy ( ) Autosomal dominant nocturnal frontal lobe epilepsy ( ) Congenital stationary night blindness ( ) Achromatopsia ( ) Cone-rod dystrophy ( )
UniProt ID	CABP4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00036 ; PF13499
Sequence	MTTEQARGQQGPNLAIGRQKPPAGVVTPKSDAEEPPLTRKRSKKERGLRGSRKRTGSSGE QTGPEAPGSSNNPPSTGEGPAGAPPASPGPASSRQSHRHRPDSLHDAAQRTYGPLLNRVF GKDRELGPEELDELQAAFEEFDTDRDGYISHRELGDCMRTLGYMPTEMELLEVSQHIKMR MGGRVDFEEFVELIGPKLREETAHMLGVRELRIAFREFDRDRDGRITVAELREAVPALLG EPLAGPELDEMLREVDLNGDGTVDFDEFVMMLSRH
Function	Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission. Modulator of CACNA1D and CACNA1F, suppressing the calcium-dependent inactivation and shifting the activation range to more hyperpolarized voltages.
Tissue Specificity	Expressed in retina and in the inner hair cells (IHC) of the cochlea.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cone-rod synaptic disorder, congenital nonprogressive	DIS9ZCRA	Definitive	Autosomal recessive	[1]
Congenital stationary night blindness 2A	DISA57KI	Strong	Biomarker	[2]
Myopia	DISK5S60	Strong	Biomarker	[3]
Night blindness	DIS335K9	Strong	Genetic Variation	[4]
Leber congenital amaurosis	DISMGH8F	moderate	Genetic Variation	[5]
Leber congenital amaurosis 1	DISY2B33	moderate	Genetic Variation	[5]
Retinopathy	DISB4B0F	moderate	Biomarker	[6]
Autosomal dominant nocturnal frontal lobe epilepsy	DISE3C4O	Supportive	Autosomal dominant	[7]
Congenital stationary night blindness	DISX0CWK	Supportive	Autosomal dominant	[8]
Achromatopsia	DISKL51I	Limited	CausalMutation	[9]
Cone-rod dystrophy	DISY9RWN	Limited	Genetic Variation	[9]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calcium-binding protein 4 (CABP4).	[10]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Calcium-binding protein 4 (CABP4).	[11]
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References

1	A novel homozygous nonsense mutation in CABP4 causes congenital cone-rod synaptic disorder. Invest Ophthalmol Vis Sci. 2009 May;50(5):2344-50. doi: 10.1167/iovs.08-2553. Epub 2008 Dec 13.
2	Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nat Neurosci. 2004 Oct;7(10):1079-87. doi: 10.1038/nn1320. Epub 2004 Sep 26.
3	Development of Refractive Errors-What Can We Learn From Inherited Retinal Dystrophies?.Am J Ophthalmol. 2017 Oct;182:81-89. doi: 10.1016/j.ajo.2017.07.008. Epub 2017 Jul 25.
4	Complex regulation of voltage-dependent activation and inactivation properties of retinal voltage-gated Cav1.4 L-type Ca2+ channels by Ca2+-binding protein 4 (CaBP4).J Biol Chem. 2012 Oct 19;287(43):36312-21. doi: 10.1074/jbc.M112.392811. Epub 2012 Aug 30.
5	A null mutation in CABP4 causes Leber's congenital amaurosis-like phenotype.Mol Vis. 2010 Feb 10;16:207-12.
6	Multimodal imaging in CABP4-related retinopathy.Ophthalmic Genet. 2017 Sep-Oct;38(5):459-464. doi: 10.1080/13816810.2017.1289543. Epub 2017 Mar 1.
7	Exome sequencing identified a novel missense mutation c.464G>A (p.G155D) in Ca(2+)-binding protein 4 (CABP4) in a Chinese pedigree with autosomal dominant nocturnal frontal lobe epilepsy. Oncotarget. 2017 Sep 5;8(45):78940-78947. doi: 10.18632/oncotarget.20694. eCollection 2017 Oct 3.
8	Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness. Am J Hum Genet. 2006 Oct;79(4):657-67. doi: 10.1086/508067. Epub 2006 Aug 23.
9	Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
10	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
11	The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.