ONECUT3
protein-codingone cut homeobox 3, the group of CUT class homeoboxes and pseudogenes
Gene summary
Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.5 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 ONECUT3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080488.2. 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 | 22 | 22 | ||||
| missense | 105 | 3 | 108 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 105 | 25 | 0 | 130 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073957.1 | 2 | MANE Select | |
| Ensembl | ENSP00000371786.4 | 2 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| onecut3a | Danio rerio | Structure: hepatic duct Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell differentiation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
Cellular Component
- nucleus
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382349
- Coding exons
- 2
- Length
- 28616
- Individuals with no LoFs
- 115981
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 115983
- p
- 0.00000862
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.30 | 50 | 83.6 | 0.598 | 0.00000392 | 3056 |
| Missense (PolyPhen) | 8 | 38.824 | 0.20606 | 517 | ||
| Synonymous | 0.531 | 32 | 36.1 | 0.887 | 0.00000170 | 1139 |
| Loss of Function | 0.399 | 4 | 4.96 | 0.807 | 2.13e-7 | 104 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000030 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000096 | 0.0000096 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator. Binds the consensus DNA sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR (By similarity). {ECO:0000250}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.341
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |