Details of Drug Off-Target (DOT)

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

• DOT Name: Immunoglobulin lambda-like polypeptide 1 (IGLL1)
• Synonyms: CD179 antigen-like family member B; Ig lambda-5; Immunoglobulin omega polypeptide; Immunoglobulin-related protein 14.1; CD antigen CD179b
• Gene Name: IGLL1
• Related Disease:
  Agammaglobulinemia
  Bruton-type agammaglobulinemia
  Fatty liver disease
  Agammaglobulinemia 2, autosomal recessive
  Autosomal agammaglobulinemia
  Neoplasm
• UniProt ID: IGLL1_HUMAN
• PDB ID: 2H32; 2H3N; 2LKQ
• Pfam ID: PF07654
• Sequence:
  MRPGTGQGGLEAPGEPGPNLRQRWPLLLLGLAVVTHGLLRPTAASQSRALGPGAPGGSSR
  SSLRSRWGRFLLQRGSWTGPRCWPRGFQSKHNSVTHVFGSGTQLTVLSQPKATPSVTLFP
  PSSEELQANKATLVCLMNDFYPGILTVTWKADGTPITQGVEMTTPSKQSNNKYAASSYLS
  LTPEQWRSRRSYSCQVMHEGSTVEKTVAPAECS
• Function: Critical for B-cell development.
• Tissue Specificity: Expressed only in pre-B-cells and a special B-cell line (which is surface Ig negative).
• KEGG Pathway: Primary immunodeficiency (hsa05340)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Agammaglobulinemia	DISXMS80	Strong	Biomarker	[1]
Bruton-type agammaglobulinemia	DISQ5ZYP	Strong	Genetic Variation	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Agammaglobulinemia 2, autosomal recessive	DISVVVF2	Moderate	Autosomal recessive	[4]
Autosomal agammaglobulinemia	DISRW8BT	Supportive	Autosomal dominant	[5]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[6]

1 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 Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[7]

6 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 Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[10]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Immunoglobulin lambda-like polypeptide 1 (IGLL1).	[13]

References

• [1] Autosomal recessive agammaglobulinemia associated with an IGLL1 gene missense mutation.Ann Allergy Asthma Immunol. 2016 Oct;117(4):439-441. doi: 10.1016/j.anai.2016.07.038. Epub 2016 Aug 27.
• [2] Novel Igalpha (CD79a) gene mutation in a Turkish patient with B cell-deficient agammaglobulinemia. Am J Med Genet. 2002 Apr 1;108(4):333-6. doi: 10.1002/ajmg.10296.
• [3] Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK.Int J Mol Sci. 2018 Jan 24;19(2):348. doi: 10.3390/ijms19020348.
• [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] Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. J Exp Med. 1998 Jan 5;187(1):71-7. doi: 10.1084/jem.187.1.71.
• [6] Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas: implications for lymphomagenesis.Leuk Lymphoma. 2006 Aug;47(8):1523-34. doi: 10.1080/10428190600612909.
• [7] 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.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [12] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [13] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.