IKZF3

IKAROS family zinc finger 3, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 17:39757717-39864312

Previous symbols: [ "ZNFN1A3" ]

Links

ENSG00000161405 ∙ NCBI:22806 ∙ OMIM:606221 ∙ HGNC:13178 ∙ Uniprot:Q9UKT9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 84 (Limited), mode of inheritance: AD
• immunodeficiency 84 (Strong), mode of inheritance: AD
• immunodeficiency 84 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 84	AD	Allergy/Immunology/Infectious; Oncologic	Individuals may be susceptible to infections, and early and aggressive treatment of infections may be beneficial; Lymphoma has been described, and awareness may allow early detection and management; BMT has been described	Allergy/Immunology/Infectious; Oncologic	34155405

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IKZF3 gene.

• Inborn genetic diseases (15 variants)
• not provided (5 variants)
• not specified (3 variants)
• Immunodeficiency 84 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IKZF3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			17	2		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1		2	3
Total	0	0	18	4	3

Variants in IKZF3

This is a list of pathogenic ClinVar variants found in the IKZF3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-39765833-G-C			Uncertain significance (Aug 09, 2021)
17-39766006-G-A		not specified	Benign (Jan 24, 2024)
17-39766023-T-C		not specified	Likely benign (Dec 15, 2021)
17-39766038-G-A		not specified	Uncertain significance (Jul 25, 2023)
17-39766042-T-A			Uncertain significance (Nov 22, 2022)
17-39766133-C-T		not specified	Uncertain significance (Nov 30, 2021)
17-39766172-C-G		not specified	Uncertain significance (Nov 16, 2021)
17-39766242-C-T		not specified	Uncertain significance (Aug 02, 2021)
17-39766245-G-C		not specified	Uncertain significance (Jan 23, 2023)
17-39766277-C-T		not specified	Uncertain significance (Nov 06, 2023)
17-39766338-G-A		Immunodeficiency 84	Uncertain significance (Dec 02, 2022)
17-39766369-G-A			Benign/Likely benign (Feb 01, 2024)
17-39766411-C-A		not specified	Uncertain significance (Jun 30, 2022)
17-39766484-C-T		not specified	Uncertain significance (Apr 25, 2022)
17-39788294-G-A		not specified	Uncertain significance (Oct 12, 2022)
17-39788305-T-C		not specified	Uncertain significance (Feb 22, 2023)
17-39791533-C-G		Immunodeficiency 84	Pathogenic (Jul 27, 2021)
17-39791538-T-C		Immunodeficiency 84	Uncertain significance (Mar 11, 2022)
17-39792684-C-T		not specified	Uncertain significance (Sep 27, 2021)
17-39792781-C-T		not specified	Uncertain significance (Sep 27, 2022)
17-39792801-A-T		not specified	Uncertain significance (Jan 23, 2023)
17-39792821-T-G		not specified	Uncertain significance (Nov 30, 2022)
17-39792853-C-T		not specified	Uncertain significance (Nov 14, 2023)
17-39792868-T-A		Immunodeficiency 84 • not specified	Uncertain significance (Oct 02, 2023)
17-39792868-T-C		not specified	Uncertain significance (May 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IKZF3	protein_coding	protein_coding	ENST00000346872	8	99244

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.984	0.0158	125723	0	5	125728	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.14	203	309	0.657	0.0000185	3420
Missense in Polyphen		47	137.84	0.34097		1481
Synonymous	0.374	105	110	0.955	0.00000695	892
Loss of Function	3.89	2	21.4	0.0934	0.00000106	286

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:10369681}.
• Pathway: il-2 receptor beta chain in t cell activation;IL2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.211

Intolerance Scores

• loftool: 0.116
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.56

Haploinsufficiency Scores

• pHI: 0.786
• hipred: Y
• hipred_score: 0.809
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.853

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ikzf3
• Phenotype: renal/urinary system phenotype; immune system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;mesoderm development;response to bacterium;regulation of B cell proliferation;B cell activation;regulation of apoptotic process;regulation of B cell differentiation;regulation of lymphocyte differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;identical protein binding;protein homodimerization activity;sequence-specific DNA binding;transcription regulatory region DNA binding;metal ion binding;protein heterodimerization activity