Details of Drug Off-Target (DOT)

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

• DOT Name: Crooked neck-like protein 1 (CRNKL1)
• Synonyms: Crooked neck homolog; hCrn
• Gene Name: CRNKL1
• Related Disease:
  Hepatitis A virus infection
  Advanced cancer
  Cleft palate
  Colitis
  Crohn disease
  Cutaneous melanoma
  Cutaneous squamous cell carcinoma
  Esophageal adenocarcinoma
  Familial multiple trichoepithelioma
  Inflammatory bowel disease
  Isolated cleft palate
  Non-alcoholic fatty liver disease
  Pulmonary fibrosis
  Ulcerative colitis
  Cleft lip
  Isolated cleft lip
  Neoplasm
• UniProt ID: CRNL1_HUMAN
• PDB ID: 5MQF; 5XJC; 5YZG; 5Z56; 5Z57; 5Z58; 6FF4; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6ZYM; 7A5P; 7ABI; 7DVQ; 7QTT; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF02184
• Sequence:
  MTATVENLTFQKDTLGNAVDKNTSRLELRSYSLAGRHGSTEPLVLAWSSQFRRLTWGCAL
  DALHRSPCVAASQHGVTHLIRSSRTPHSTRCRKEDAQPGHHGNGAASVTAQARGQRSVLQ
  VPLPVPRSCLFSESFVVSVSSQSRFLASVPGTGVQRSTAADMAASTAAGKQRIPKVAKVK
  NKAPAEVQITAEQLLREAKERELELLPPPPQQKITDEEELNDYKLRKRKTFEDNIRKNRT
  VISNWIKYAQWEESLKEIQRARSIYERALDVDYRNITLWLKYAEMEMKNRQVNHARNIWD
  RAITTLPRVNQFWYKYTYMEEMLGNVAGARQVFERWMEWQPEEQAWHSYINFELRYKEVD
  RARTIYERFVLVHPDVKNWIKYARFEEKHAYFAHARKVYERAVEFFGDEHMDEHLYVAFA
  KFEENQKEFERVRVIYKYALDRISKQDAQELFKNYTIFEKKFGDRRGIEDIIVSKRRFQY
  EEEVKANPHNYDAWFDYLRLVESDAEAEAVREVYERAIANVPPIQEKRHWKRYIYLWINY
  ALYEELEAKDPERTRQVYQASLELIPHKKFTFAKMWILYAQFEIRQKNLSLARRALGTSI
  GKCPKNKLFKVYIELELQLREFDRCRKLYEKFLEFGPENCTSWIKFAELETILGDIDRAR
  AIYELAISQPRLDMPEVLWKSYIDFEIEQEETERTRNLYRRLLQRTQHVKVWISFAQFEL
  SSGKEGSLTKCRQIYEEANKTMRNCEEKEERLMLLESWRSFEEEFGTASDKERVDKLMPE
  KVKKRRKVQTDDGSDAGWEEYFDYIFPEDAANQPNLKLLAMAKLWKKQQQEKEDAEHHPD
  EDVDESES
• Function: Involved in pre-mRNA splicing process. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• Tissue Specificity: Widely expressed . Highly expressed in testis . Not detected in brain and lung .
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis A virus infection	DISUMFQV	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cleft palate	DIS6G5TF	Strong	Biomarker	[3]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[2]
Cutaneous melanoma	DIS3MMH9	Strong	Genetic Variation	[5]
Cutaneous squamous cell carcinoma	DIS3LXUG	Strong	Genetic Variation	[5]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[6]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[6]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[2]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[3]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[7]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[8]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[2]
Cleft lip	DISV3XW6	moderate	Biomarker	[3]
Isolated cleft lip	DIS2O2JV	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]

1 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 Crooked neck-like protein 1 (CRNKL1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Crooked neck-like protein 1 (CRNKL1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Crooked neck-like protein 1 (CRNKL1).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Crooked neck-like protein 1 (CRNKL1).	[13]

References

• [1] Direct sequencing of hepatitis A virus strains isolated during an epidemic in France.Appl Environ Microbiol. 1995 Nov;61(11):3977-80. doi: 10.1128/aem.61.11.3977-3980.1995.
• [2] Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease.Aliment Pharmacol Ther. 2013 Mar;37(5):546-54. doi: 10.1111/apt.12218. Epub 2013 Jan 24.
• [3] Wnt9b is the mutated gene involved in multifactorial nonsyndromic cleft lip with or without cleft palate in A/WySn mice, as confirmed by a genetic complementation test.Birth Defects Res A Clin Mol Teratol. 2006 Aug;76(8):574-9. doi: 10.1002/bdra.20302.
• [4] Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis.PLoS One. 2017 Apr 24;12(4):e0175935. doi: 10.1371/journal.pone.0175935. eCollection 2017.
• [5] Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.Nat Biotechnol. 2016 Feb;34(2):155-63. doi: 10.1038/nbt.3391. Epub 2015 Nov 30.
• [6] Protein coding gene CRNKL1 as a potential prognostic biomarker in esophageal adenocarcinoma.Artif Intell Med. 2017 Feb;76:1-6. doi: 10.1016/j.artmed.2017.01.002. Epub 2017 Jan 22.
• [7] Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study.APMIS. 2017 Nov;125(11):962-973. doi: 10.1111/apm.12742.
• [8] Cytokine-like factor 1 gene expression is enriched in idiopathic pulmonary fibrosis and drives the accumulation of CD4+ T cells in murine lungs: evidence for an antifibrotic role in bleomycin injury.Am J Pathol. 2012 May;180(5):1963-78. doi: 10.1016/j.ajpath.2012.01.010. Epub 2012 Mar 16.
• [9] Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia.BMC Cancer. 2016 Apr 14;16:271. doi: 10.1186/s12885-016-2303-4.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.