Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKOIR0G)

• DOT Name: Protein MFI (C11ORF65)
• Synonyms: Mitochondrial fission factor interactor
• Gene Name: C11ORF65
• Related Disease:
  Cutaneous melanoma
  Hereditary neoplastic syndrome
  Ataxia-telangiectasia
  Uterine fibroids
  Hereditary breast ovarian cancer syndrome
• UniProt ID: MFI_HUMAN
• Sequence:
  MPWKEESEFTKQDKAARVIQQAWKSFLNVAIFQHFKSLIDLRRQGEPRQIVKYINPKEAE
  LLDAAAGIHVRFRLGGVKFPPDIYYKIFTHRPIEDLCANSPRNYAKLPAKHTSHNKNDHL
  QEEDHSGWYHRIENNGWRPVSDTFWLSTDGMVVEDKKESEFHFSKLKRRQDLEKKRKLRK
  IEWMRQMYYSGSLEAKSTHHETLGLIHTATKGLIRAFEDGGIDSVMEWEVDEVLNWTNTL
  NFDEYIASWKEIATSNSSANFKGFRFNQAQKNIYNYGGDISKMQMGIPDDTYYENVYQEP
  NVTRLTPDSTYGL
• Function: Acts as an inhibitor of mitochondrial fission. Interacts with MFF and prevents DNM1L recruitment to mitochondria, promoting a more fused mitochondrial network.
• Tissue Specificity: Enriched in the pancreatic beta cell and the testis and is expressed at low levels in other tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[1]
Hereditary neoplastic syndrome	DISGXLG5	Definitive	CausalMutation	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	CausalMutation	[3]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[4]
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein MFI (C11ORF65).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein MFI (C11ORF65).	[7]

References

• [1] Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.Nat Commun. 2018 Nov 14;9(1):4774. doi: 10.1038/s41467-018-06649-5.
• [2] Pathogenic Germline Variants in 10,389 Adult Cancers.Cell. 2018 Apr 5;173(2):355-370.e14. doi: 10.1016/j.cell.2018.03.039.
• [3] Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.JAMA. 2018 Jun 19;319(23):2401-2409. doi: 10.1001/jama.2018.6228.
• [4] Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.Nat Commun. 2019 Oct 24;10(1):4857. doi: 10.1038/s41467-019-12536-4.
• [5] Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.Hum Mutat. 2016 Jul;37(7):640-52. doi: 10.1002/humu.22972. Epub 2016 Mar 18.
• [6] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.