IKZF1

IKAROS family zinc finger 1, the group of Zinc fingers C2H2-type|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 7:50304068-50405101

Previous symbols: [ "ZNFN1A1" ]

Links

ENSG00000185811 ∙ NCBI:10320 ∙ OMIM:603023 ∙ HGNC:13176 ∙ Uniprot:Q13422 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pancytopenia due to IKZF1 mutations (Supportive), mode of inheritance: AD
• pancytopenia due to IKZF1 mutations (Definitive), mode of inheritance: AD
• pancytopenia due to IKZF1 mutations (Strong), mode of inheritance: AD
• pancytopenia due to IKZF1 mutations (Strong), mode of inheritance: AD
• autoimmune disease (Moderate), mode of inheritance: AD
• pancytopenia due to IKZF1 mutations (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency, common variable, 13	AD	Allergy/Immunology/Infectious; Oncologic	Individuals may be susceptible to severe and recurrent bacterial infections, and prophylaxis and early and aggressive treatment of infections may be beneficial; Acute lymphoblastic leukemia has been described, and awareness may allow early detection and management	Allergy/Immunology/Infectious; Oncologic	21548011; 26981933

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IKZF1 gene.

• Pancytopenia due to IKZF1 mutations (5 variants)
• not provided (3 variants)
• Inherited Immunodeficiency Diseases (2 variants)
• Acute lymphoid leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IKZF1 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			43	33	7	83
missense	4	6	111	1	2	124
nonsense	2	2	3			7
start loss			1			1
frameshift		4	3			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)		1	2			3
splice region			7	1		8
non coding			14	4	17	35
Total	6	13	180	38	26

Variants in IKZF1

This is a list of pathogenic ClinVar variants found in the IKZF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-50304536-G-C			Benign (Feb 18, 2020)
7-50304819-G-A			Uncertain significance (Jul 18, 2021)
7-50319063-T-C			Uncertain significance (May 05, 2022)
7-50319068-G-A			Uncertain significance (Sep 19, 2018)
7-50319076-G-A			Benign (Sep 10, 2023)
7-50319087-T-C		Acute lymphoid leukemia	Uncertain significance (Sep 23, 2023)
7-50319094-A-G			Likely benign (Dec 13, 2023)
7-50319106-G-A		not specified	Uncertain significance (Jan 18, 2019)
7-50327619-ACTT-A			Likely benign (Feb 05, 2023)
7-50327622-T-A			Uncertain significance (Mar 27, 2023)
7-50327624-T-C			Uncertain significance (May 16, 2023)
7-50327647-G-A			Uncertain significance (Apr 02, 2023)
7-50327649-C-A			Uncertain significance (Nov 11, 2023)
7-50327652-C-A			Uncertain significance (Mar 14, 2022)
7-50327652-C-G			Uncertain significance (Oct 07, 2023)
7-50327653-C-A			Uncertain significance (Jul 29, 2022)
7-50327653-C-T			Uncertain significance (Dec 02, 2023)
7-50327659-G-A			Uncertain significance (Mar 14, 2022)
7-50327660-C-T			Uncertain significance (Oct 10, 2023)
7-50327661-G-A		Pancytopenia due to IKZF1 mutations	Conflicting classifications of pathogenicity (Sep 20, 2023)
7-50327671-A-T			Uncertain significance (Jun 20, 2023)
7-50327675-G-A			Uncertain significance (Mar 29, 2022)
7-50327676-G-A			Uncertain significance (Sep 10, 2023)
7-50327678-C-T			Uncertain significance (Aug 12, 2023)
7-50327679-G-A			Uncertain significance (Dec 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IKZF1	protein_coding	protein_coding	ENST00000439701	6	129080

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00140	123730	0	1	123731	0.00000404

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.38	148	317	0.467	0.0000203	3154
Missense in Polyphen		22	122.16	0.18009		1153
Synonymous	0.885	127	140	0.905	0.0000107	885
Loss of Function	4.05	0	19.1	0.00	9.80e-7	212

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000179	0.00000892
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta- globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067). {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, ECO:0000269|PubMed:19141594}.
• Disease: DISEASE: Note=Defects in IKZF1 are frequent occurrences (28.6%) in acute lymphoblasic leukemia (ALL). Such alterations or deletions lead to poor prognosis for ALL.; DISEASE: Note=Chromosomal aberrations involving IKZF1 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;7)(q27;p12), with BCL6.; DISEASE: Immunodeficiency, common variable, 13 (CVID13) [MIM:616873]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. CVID13 is an autosomal dominant disease associated with a striking decrease in B-cell numbers. {ECO:0000269|PubMed:21548011, ECO:0000269|PubMed:26981933}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hematopoietic Stem Cell Differentiation;Development of pulmonary dendritic cells and macrophage subsets;Calcineurin-regulated NFAT-dependent transcription in lymphocytes (Consensus)

Recessive Scores

• pRec: 0.466

Haploinsufficiency Scores

• pHI: 0.623
• hipred: Y
• hipred_score: 0.825
• ghis: 0.662

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ikzf1
• Phenotype: digestive/alimentary phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; 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); neoplasm; endocrine/exocrine gland phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ikzf1
• Affected structure: thymus
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: chromatin organization;cell cycle;mesoderm development;lymphocyte differentiation;erythrocyte differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;protein heterooligomerization
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear pericentric heterochromatin;protein-containing complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;protein domain specific binding;transcription regulatory region DNA binding;metal ion binding