OVOL2
protein-codingovo like zinc finger 2, the group of Zinc fingers C2H2-type
Gene summary
This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy. [provided by RefSeq, Apr 2016]
- ZNF339
- CHED1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~102.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007378
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007378
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0007378
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007378
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0020364
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: Ophthalmologic
Rationale: Individuals are at risk of glaucoma prior to or following corneal transplantation, and surveillance and early treatment may be beneficial
Comments: A variant in the OVOL2 promoter have been described in Corneal dystrophy, posterior polymorphous, 1
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OVOL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021220.4. 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 | 6 | 6 | ||||
| missense | 39 | 2 | 2 | 43 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 41 | 8 | 2 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067043.2 | 4 | MANE Select | |
| Ensembl | ENSP00000278780.5 | 4 | MANE Select | |
| RefSeq | NP_001290390.1 | 2 | Standard | |
| RefSeq | NP_001290391.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- angiogenesis
- neural crest cell migration
- neural fold formation
- heart looping
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- chromatin binding
- sequence-specific DNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000278780
- Coding exons
- 4
- Length
- 102210
- Individuals with no LoFs
- 125185
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125194
- p
- 0.0000359
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.09 | 114 | 152 | 0.751 | 0.00000936 | 1779 |
| Missense (PolyPhen) | 55 | 79.347 | 0.69315 | 764 | ||
| Synonymous | 0.769 | 59 | 67.0 | 0.880 | 0.00000449 | 522 |
| Loss of Function | 2.36 | 1 | 8.37 | 0.119 | 3.55e-7 | 113 |
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 | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000071 | 0.000071 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Zinc-finger transcription repressor factor (PubMed:19700410). Plays a critical role in maintaining the identity of epithelial lineages by suppressing epithelial-to mesenchymal transition (EMT) mainly through the repression of ZEB1, an EMT inducer (By similarity). Positively regulates neuronal differentiation (By similarity). Suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing MYC and NOTCH1 (PubMed:19700410). Important for the correct development of primordial germ cells in embryos (By similarity). {ECO:0000250|UniProtKB:Q8CIV7, ECO:0000269|PubMed:19700410}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.251
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.288
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |