Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5DHGI8)

DOT Name	Cryptic protein (CFC1)
Synonyms	Cryptic family protein 1
Gene Name	CFC1
Related Disease	Malaria ( ) Metabolic disorder ( ) Advanced cancer ( ) Alzheimer disease ( ) Aromatase excess syndrome ( ) Blast phase chronic myelogenous leukemia, BCR-ABL1 positive ( ) Cardiac disease ( ) Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency ( ) Gastric adenocarcinoma ( ) Heterotaxy, visceral, 2, autosomal ( ) Lymphoma, non-Hodgkin, familial ( ) Myelodysplastic syndrome ( ) Neoplasm ( ) Non-hodgkin lymphoma ( ) Right atrial isomerism ( ) Schizophrenia ( ) Transposition of the great arteries ( ) Tuberculosis ( ) Visceral heterotaxy ( ) Atrial septal defect ( ) Cardiofaciocutaneous syndrome ( ) Congenital heart disease ( ) Neuroblastoma ( )
UniProt ID	CFC1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF09443
Sequence	MTWRHHVRLLFTVSLALQIINLGNSYQREKHNGGREEVTKVATQKHRQSPLNWTSSHFGE VTGSAEGWGPEEPLPYSRAFGEGASARPRCCRNGGTCVLGSFCVCPAHFTGRYCEHDQRR SECGALEHGAWTLRACHLCRCIFGALHCLPLQTPDRCDPKDFLASHAHGPSAGGAPSLLL LLPCALLHRLLRPDAPAHPRSLVPSVLQRERRPCGRPGLGHRL
Function	NODAL coreceptor involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation.
Reactome Pathway	Regulation of signaling by NODAL (R-HSA-1433617 ) Signaling by NODAL (R-HSA-1181150 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Metabolic disorder	DIS71G5H	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Aromatase excess syndrome	DIS1N9UV	Strong	Biomarker	[5]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Genetic Variation	[6]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[7]
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	DISMTRY0	Strong	Biomarker	[8]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[9]
Heterotaxy, visceral, 2, autosomal	DISPJ9QY	Strong	Autosomal dominant	[10]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[11]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[13]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[11]
Right atrial isomerism	DIS2SZ2Q	Strong	Biomarker	[14]
Schizophrenia	DISSRV2N	Strong	Biomarker	[15]
Transposition of the great arteries	DISPXJ8X	Strong	Biomarker	[7]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[16]
Visceral heterotaxy	DIS1DV90	Strong	Genetic Variation	[17]
Atrial septal defect	DISJT76B	Limited	Genetic Variation	[18]
Cardiofaciocutaneous syndrome	DISZJKSC	Limited	Biomarker	[19]
Congenital heart disease	DISQBA23	Limited	Genetic Variation	[20]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[21]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Cryptic protein (CFC1).	[22]
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References

1	Cryptic genetic diversity within the Anopheles nili group of malaria vectors in the equatorial forest area of Cameroon (Central Africa).PLoS One. 2013;8(3):e58862. doi: 10.1371/journal.pone.0058862. Epub 2013 Mar 14.
2	Drug off-target effects predicted using structural analysis in the context of a metabolic network model.PLoS Comput Biol. 2010 Sep 23;6(9):e1000938. doi: 10.1371/journal.pcbi.1000938.
3	A genome wide dosage suppressor network reveals genomic robustness.Nucleic Acids Res. 2017 Jan 9;45(1):255-270. doi: 10.1093/nar/gkw1148. Epub 2016 Nov 29.
4	Identifying unexpected therapeutic targets via chemical-protein interactome.PLoS One. 2010 Mar 8;5(3):e9568. doi: 10.1371/journal.pone.0009568.
5	Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression.J Clin Endocrinol Metab. 2013 Dec;98(12):E2013-21. doi: 10.1210/jc.2013-2520. Epub 2013 Sep 24.
6	Acquisition of genomic events leading to lymphoblastic transformation in a rare case of myeloproliferative neoplasm with BCR-JAK2 fusion transcript.Eur J Haematol. 2016 Oct;97(4):399-402. doi: 10.1111/ejh.12752. Epub 2016 Mar 26.
7	CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle.Am J Hum Genet. 2002 Mar;70(3):776-80. doi: 10.1086/339079. Epub 2002 Jan 17.
8	Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.J Clin Endocrinol Metab. 1981 Dec;53(6):1193-8. doi: 10.1210/jcem-53-6-1193.
9	Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements.Nat Commun. 2014 Jul 10;5:4361. doi: 10.1038/ncomms5361.
10	Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
11	Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus.Nature. 1984 Jan 26-Feb 1;307(5949):334-40. doi: 10.1038/307334a0.
12	Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500K SNP arrays identifies significant regions of deletion and uniparental disomy.Exp Hematol. 2009 Feb;37(2):215-224. doi: 10.1016/j.exphem.2008.10.012.
13	Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples.Nat Med. 2017 Mar;23(3):376-385. doi: 10.1038/nm.4279. Epub 2017 Feb 6.
14	A role of the cryptic gene in the correct establishment of the left-right axis.Curr Biol. 1999 Nov 18;9(22):1339-42. doi: 10.1016/s0960-9822(00)80059-7.
15	Possible genetic and epigenetic links between human inner speech, schizophrenia and altruism.Brain Res. 2012 Oct 2;1476:38-57. doi: 10.1016/j.brainres.2012.02.074. Epub 2012 Mar 6.
16	Validating a 14-Drug Microtiter Plate Containing Bedaquiline and Delamanid for Large-Scale Research Susceptibility Testing of Mycobacterium tuberculosis.Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00344-18. doi: 10.1128/AAC.00344-18. Print 2018 Sep.
17	Duplication and deletion of CFC1 associated with heterotaxy syndrome.DNA Cell Biol. 2015 Feb;34(2):101-6. doi: 10.1089/dna.2014.2616. Epub 2014 Nov 25.
18	Mutations in the EGF-CFC gene cryptic are an infrequent cause of congenital heart disease.Pediatr Cardiol. 2006 Nov-Dec;27(6):695-8. doi: 10.1007/s00246-006-1082-0. Epub 2006 Oct 27.
19	A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects.Hum Genet. 2002 May;110(5):422-8. doi: 10.1007/s00439-002-0709-3. Epub 2002 Apr 10.
20	CFC1 mutations in Chinese children with congenital heart disease.Int J Cardiol. 2011 Jan 7;146(1):86-8. doi: 10.1016/j.ijcard.2009.07.034. Epub 2009 Oct 23.
21	CFC1 is a cancer stemness-regulating factor in neuroblastoma.Oncotarget. 2017 Jul 11;8(28):45046-45059. doi: 10.18632/oncotarget.18464.
22	Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.