IKZF4
protein-codingIKAROS family zinc finger 4, the group of Zinc fingers C2H2-type
Gene summary
Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Eos, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]
- ZNFN1A4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IKZF4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022465.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 68 | 68 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 69 | 0 | 0 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071910.3 | 8 | MANE Select | |
| Ensembl | ENSP00000448419.1 | 8 | MANE Select | |
| RefSeq | NP_001338018.1 | 8 | Standard | |
| RefSeq | NP_001338019.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription, DNA-templated
- positive regulation of transcription by RNA polymerase II
- protein homooligomerization
- protein heterooligomerization
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- zinc ion binding
- protein domain specific binding
- bHLH transcription factor binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear body
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262032
- Coding exons
- 8
- Length
- 30777
- Individuals with no LoFs
- 124629
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 124637
- p
- 0.0000321
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.41 | 228 | 356 | 0.641 | 0.0000214 | 3800 |
| Missense (PolyPhen) | 39 | 123.37 | 0.31613 | 1255 | ||
| Synonymous | 0.575 | 128 | 137 | 0.937 | 0.00000764 | 1197 |
| Loss of Function | 3.59 | 3 | 20.6 | 0.146 | 0.00000110 | 253 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.000062 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000035 | 0.000033 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-binding sequence. Transcriptional repressor. Interacts with SPI1 and MITF to repress transcription of the CTSK and ACP5 promoters via recruitment of corepressors SIN3A and CTBP2. May be involved in the development of central and peripheral nervous systems. Essential for the inhibitory function of regulatory T- cells (Treg). Mediates FOXP3-mediated gene silencing in regulatory T-cells (Treg) via recruitment of corepressor CTBP1 (By similarity). {ECO:0000250|UniProtKB:Q8C208, ECO:0000269|PubMed:10978333, ECO:0000269|PubMed:12015313, ECO:0000269|PubMed:12444977}.;
Recessive Scores
- pRec
- 0.267
Intolerance Scores
- LoFtool
- 0.218
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |