ONECUT1
protein-codingone cut homeobox 1, the group of CUT class homeoboxes and pseudogenes
Gene summary
This gene encodes a member of the Cut homeobox family of transcription factors. Expression of the encoded protein is enriched in the liver, where it stimulates transcription of liver-expressed genes, and antagonizes glucocorticoid-stimulated gene transcription. This gene may influence a variety of cellular processes including glucose metabolism, cell cycle regulation, and it may also be associated with cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
- HNF6
- HNF6A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0016391
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016391
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ONECUT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004498.4. 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 | 1 | 1 | 2 | |||
| missense | 58 | 58 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 59 | 1 | 0 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004489.1 | 2 | MANE Select | |
| Ensembl | ENSP00000302630.4 | 2 | MANE Select | |
| Ensembl | ENSP00000476168.1 | 3 | Standard | |
| Ensembl | ENSP00000805587.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| onecut1 | Danio rerio | Structure: intrahepatic bile duct Quality: dilated abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Maturity onset diabetes of the young - Homo sapiens (human)
- Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
- Endoderm Differentiation
- FOXM1 transcription factor network
Biological Process
- liver development
- regulation of cell-matrix adhesion
- epithelial cell development
- glucose metabolic process
- regulation of transcription, DNA-templated
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305901
- Coding exons
- 2
- Length
- 33637
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125719
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.524 | 237 | 261 | 0.909 | 0.0000123 | 3032 |
| Missense (PolyPhen) | 57 | 90.757 | 0.62805 | 1040 | ||
| Synonymous | -0.363 | 115 | 110 | 1.04 | 0.00000527 | 928 |
| Loss of Function | 2.45 | 2 | 10.6 | 0.188 | 5.24e-7 | 115 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator. Binds the consensus sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR. Important for liver genes transcription.;
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- LoFtool
- 0.0302
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.583
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |