Molecule Information

General Information of the Molecule (ID: Mol00433)

• Name: Zinc finger protein Aiolos (IKZF3) ,Homo sapiens
• Synonyms: Ikaros family zinc finger protein 3; ZNFN1A3
• Molecule Type: Protein
• Gene Name: IKZF3
• Gene ID: 22806
• Location: chr17:39757718-39864312[-]
• Sequence:
  MEDIQTNAELKSTQEQSVPAESAAVLNDYSLTKSHEMENVDSGEGPANEDEDIGDDSMKV
  KDEYSERDENVLKSEPMGNAEEPEIPYSYSREYNEYENIKLERHVVSFDSSRPTSGKMNC
  DVCGLSCISFNVLMVHKRSHTGERPFQCNQCGASFTQKGNLLRHIKLHTGEKPFKCHLCN
  YACQRRDALTGHLRTHSVEKPYKCEFCGRSYKQRSSLEEHKERCRTFLQSTDPGDTASAE
  ARHIKAEMGSERALVLDRLASNVAKRKSSMPQKFIGEKRHCFDVNYNSSYMYEKESELIQ
  TRMMDQAINNAISYLGAEALRPLVQTPPAPTSEMVPVISSMYPIALTRAEMSNGAPQELE
  KKSIHLPEKSVPSERGLSPNNSGHDSTDTDSNHEERQNHIYQQNHMVLSRARNGMPLLKE
  VPRSYELLKPPPICPRDSVKVINKEGEVMDVYRCDHCRVLFLDYVMFTIHMGCHGFRDPF
  ECNMCGYRSHDRYEFSSHIARGEHRALLK
• Function: Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner.
• Uniprot ID: IKZF3_HUMAN
• Ensembl ID: ENSG00000161405
• HGNC ID: HGNC:13178

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Lenalidomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Multiple myeloma [1], [2]

• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Resistant Drug: Lenalidomide
• Molecule Alteration: Missense mutation; p.Q147H
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/RAS signaling pathway; Regulation; hsa04151
• In Vitro Model: Bone marrow; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
• Experiment for Drug Resistance: Longitudinal copy number aberration (CNA) analysis
• Mechanism Description: Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.

Thalidomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Multiple myeloma [1], [2]

• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Resistant Drug: Thalidomide
• Molecule Alteration: Missense mutation; p.Q147H
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/RAS signaling pathway; Regulation; hsa04151
• In Vitro Model: Bone marrow; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
• Experiment for Drug Resistance: Longitudinal copy number aberration (CNA) analysis
• Mechanism Description: Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Multiple myeloma [ICD-11: 2A83]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Multiple myeloma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.41E-01; Fold-change: 6.79E-02; Z-score: 1.28E-01
• The Studied Tissue: Peripheral blood
• The Specified Disease: Multiple myeloma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.81E-01; Fold-change: -1.69E-01; Z-score: -5.34E-01

References

• Ref 1: Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014 Jan 17;343(6168):301-5. doi: 10.1126/science.1244851. Epub 2013 Nov 29.
• Ref 2: Clonal rat parathyroid cell line expresses a parathyroid hormone-related peptide but not parathyroid hormone itself. Biochem Biophys Res Commun. 1989 Jul 14;162(1):108-15. doi: 10.1016/0006-291x(89)91969-4.