Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHF0EOJ)

• DOT Name: BPI fold-containing family B member 4 (BPIFB4)
• Synonyms: Ligand-binding protein RY2G5; Long palate, lung and nasal epithelium carcinoma-associated protein 4
• Gene Name: BPIFB4
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Carotid stenosis
  High blood pressure
  Cardiovascular disease
• UniProt ID: BPIB4_HUMAN
• Pfam ID: PF01273 ; PF02886
• Sequence:
  MWMAWCVAALSVVAVCGTSHETNTVLRVTKDVLSNAISGMLQQSDALHSALREVPLGVGD
  IPYNDFHVRGPPPVYTNGKKLDGIYQYGHIETNDNTAQLGGKYRYGEILESEGSIRDLRN
  SGYRSAENAYGGHRGLGRYRAAPVGRLHRRELQPGEIPPGVATGAVGPGGLLGTGGMLAA
  DGILAGQGGLLGGGGLLGDGGLLGGGGVLGVLGEGGILSTVQGITGLRIVELTLPRVSVR
  LLPGVGVYLSLYTRVAINGKSLIGFLDIAVEVNITAKVRLTMDRTGYPRLVIERCDTLLG
  GIKVKLLRGLLPNLVDNLVNRVLADVLPDLLCPIVDVVLGLVNDQLGLVDSLIPLGILGS
  VQYTFSSLPLVTGEFLELDLNTLVGEAGGGLIDYPLGWPAVSPKPMPELPPMGDNTKSQL
  AMSANFLGSVLTLLQKQHALDLDITNGMFEELPPLTTATLGALIPKVFQQYPESCPLIIR
  IQVLNPPSVMLQKDKALVKVLATAEVMVSQPKDLETTICLIDVDTEFLASFSTEGDKLMI
  DAKLEKTSLNLRTSNVGNFDIGLMEVLVEKIFDLAFMPAMNAVLGSGVPLPKILNIDFSN
  ADIDVLEDLLVLSA
• Function: May have the capacity to recognize and bind specific classes of odorants. May act as a carrier molecule, transporting odorants across the mucus layer to access receptor sites. May serve as a primary defense mechanism by recognizing and removing potentially harmful odorants or pathogenic microorganisms from the mucosa or clearing excess odorant from mucus to enable new odorant stimuli to be received.
• Tissue Specificity: Expressed in nasal tissue.
• Reactome Pathway: Antimicrobial peptides (R-HSA-6803157)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[1]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[1]
Carotid stenosis	DISZA8D0	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[2]
Cardiovascular disease	DIS2IQDX	moderate	Altered Expression	[1]

2 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 BPI fold-containing family B member 4 (BPIFB4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of BPI fold-containing family B member 4 (BPIFB4).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of BPI fold-containing family B member 4 (BPIFB4).	[4]

References

• [1] Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism.Eur Heart J. 2020 Jul 7;41(26):2487-2497. doi: 10.1093/eurheartj/ehz459.
• [2] Author Correction: A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling.Sci Rep. 2019 Jun 28;9(1):9574. doi: 10.1038/s41598-019-45691-1.
• [3] 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.
• [4] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [5] 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.