Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUMUSY0)

• DOT Name: Carcinoembryonic antigen-related cell adhesion molecule 16 (CEACAM16)
• Synonyms: Carcinoembryonic antigen-like 2
• Gene Name: CEACAM16
• Related Disease:
  B-cell neoplasm
  Autosomal dominant nonsyndromic hearing loss 4B
  Deafness
  Hearing loss, autosomal recessive 113
  Nonsyndromic genetic hearing loss
  Autosomal dominant nonsyndromic hearing loss 4A
  Autosomal dominant nonsyndromic hearing loss
  Hearing loss, autosomal recessive
• UniProt ID: CEA16_HUMAN
• Pfam ID: PF13895 ; PF13927 ; PF07686
• Sequence:
  MALTGYSWLLLSATFLNVGAEISITLEPAQPSEGDNVTLVVHGLSGELLAYSWYAGPTLS
  VSYLVASYIVSTGDETPGPAHTGREAVRPDGSLDIQGILPRHSGTYILQTFNRQLQTEVG
  YGHVQVHEILAQPTVLANSTALVERRDTLRLMCSSPSPTAEVRWFFNGGALPVALRLGLS
  PDGRVLARHGIRREEAGAYQCEVWNPVSVSRSEPINLTVYFGPERVAILQDSTTRTGCTI
  KVDFNTSLTLWCVSRSCPEPEYVWTFNGQALKNGQDHLNISSMTAAQEGTYTCIAKNTKT
  LLSGSASVVVKLSAAAVATMIVPVPTKPTEGQDVTLTVQGYPKDLLVYAWYRGPASEPNR
  LLSQLPSGTWIAGPAHTGREVGFPNCSLLVQKLNLTDTGRYTLKTVTVQGKTETLEVELQ
  VAPLG
• Function: Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Autosomal dominant nonsyndromic hearing loss 4B	DIS9V2II	Strong	Autosomal dominant	[2]
Deafness	DISKCLH4	Strong	Biomarker	[3]
Hearing loss, autosomal recessive 113	DIS2WSW1	Strong	Autosomal recessive	[3]
Nonsyndromic genetic hearing loss	DISZX61P	Strong	Autosomal recessive	[4]
Autosomal dominant nonsyndromic hearing loss 4A	DISBK1WH	moderate	Biomarker	[5]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[2]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[3]

3 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 Carcinoembryonic antigen-related cell adhesion molecule 16 (CEACAM16).	[6]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Carcinoembryonic antigen-related cell adhesion molecule 16 (CEACAM16).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Carcinoembryonic antigen-related cell adhesion molecule 16 (CEACAM16).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 16 (CEACAM16).	[7]

References

• [1] Gene signature in Alzheimer's disease and environmental factors: the virus chronicle.J Alzheimers Dis. 2011;27(4):809-17. doi: 10.3233/JAD-2011-110755.
• [2] Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with alpha-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4218-23. doi: 10.1073/pnas.1005842108. Epub 2011 Feb 22.
• [3] Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment. J Med Genet. 2018 Aug;55(8):555-560. doi: 10.1136/jmedgenet-2018-105349. Epub 2018 Apr 27.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Loss of mammal-specific tectorial membrane component carcinoembryonic antigen cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies.J Biol Chem. 2012 Jun 22;287(26):21584-98. doi: 10.1074/jbc.M111.320481. Epub 2012 Apr 27.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.