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
Transcripts
Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 106.
| Transcript ID | Protein ID | Coding exons | MANE Select | MANE Plus Clinical |
|---|---|---|---|---|
NM_006060.6 | NP_006051.1 | 7 | yes | - |
ENST00000331340.8 | ENSP00000331614.3 | 7 | yes | - |
NM_001220765.3 | NP_001207694.1 | 6 | - | - |
NM_001220767.2 | NP_001207696.1 | 6 | - | - |
Phenotypes
GenCC
Source:
- 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
- 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 (Supportive), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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 |
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ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (377 variants)
- Pancytopenia_due_to_IKZF1_mutations (35 variants)
- not_specified (26 variants)
- IKZF1-related_disorder (25 variants)
- Acute_lymphoid_leukemia (21 variants)
- Inherited_Immunodeficiency_Diseases (6 variants)
- Teratoma (1 variants)
- Immunodeficiency (1 variants)
- Diamond-Blackfan_anemia-like (1 variants)
- See_cases (1 variants)
- Chronic_myeloid_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. These statistics are base on transcript: NM_006060.6. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 26 | 90 | 1 | 117 | ||
| missense | 3 | 18 | 184 | 4 | 209 | |
| nonsense | 2 | 5 | 7 | 14 | ||
| start loss | 1 | 1 | ||||
| frameshift | 6 | 8 | 14 | |||
| splice donor/acceptor (+/-2bp) | 3 | 3 | 6 | |||
| Total | 5 | 32 | 229 | 94 | 1 |
Highest pathogenic variant AF is 0.00001505921
Loading clinvar variants...
GnomAD
Source:
| 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 |
|---|---|---|---|---|---|---|
| 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:
- 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
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 |
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