Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTARXZN8)

• DOT Name: Factor in the germline alpha (FIGLA)
• Synonyms: FIGalpha; Class C basic helix-loop-helix protein 8; bHLHc8; Folliculogenesis-specific basic helix-loop-helix protein; Transcription factor FIGa
• Gene Name: FIGLA
• Related Disease:
  Female hypogonadism
  Premature ovarian failure 6
• UniProt ID: FIGLA_HUMAN
• Pfam ID: PF00010
• Sequence:
  MDPAPGVLDPRAAPPALLGTPQAEVLEDVLREQFGPLPQLAAVCRLKRLPSGGYSSTENL
  QLVLERRRVANAKERERIKNLNRGFARLKALVPFLPQSRKPSKVDILKGATEYIQVLSDL
  LEGAKDSKKQDPDEQSYSNNSSESHTSSARQLSRNITQHISCAFGLKNEEEGPWADGGSG
  EPAHACRHSVMSTTEIISPTRSLDRFPEVELLSHRLPQV
• Function: Germline specific transcription factor implicated in postnatal oocyte-specific gene expression. Plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida (ZP1, ZP2 and ZP3) required for fertilization and early embryonic survival. Essential for oocytes to survive and form primordial follicles. The persistence of FIGLA in adult females suggests that it may regulate additional pathways that are essential for normal ovarian development. Binds to the E-box (5'-CANNTG-3') of the ZPs (ZP1, ZP2, ZP3) promoters.
• Tissue Specificity: Germ cells. Expressed in the fetal ovary, but not by a range of other tissues. Expression increases across mid-gestation, rising some 40-fold by the time of primordial follicle formation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Female hypogonadism	DISWASB4	moderate	Biomarker	[1]
Premature ovarian failure 6	DIS7DDVN	Moderate	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Factor in the germline alpha (FIGLA).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Factor in the germline alpha (FIGLA).	[4]

References

• [1] Bi-allelic recessive loss-of-function mutations in FIGLA cause premature ovarian insufficiency with short stature.Clin Genet. 2019 Mar;95(3):409-414. doi: 10.1111/cge.13486. Epub 2018 Dec 18.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [4] Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.