ZNF703
protein-codingzinc finger protein 703, the group of Zinc fingers C2H2-type
Gene summary
Predicted to enable DNA-binding transcription factor binding activity and zinc ion binding activity. Involved in several processes, including cellular response to estradiol stimulus; positive regulation of mammary gland epithelial cell proliferation; and regulation of transforming growth factor beta receptor signaling pathway. Located in cytoplasm and nuclear matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.2 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 ZNF703 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_025069.3. 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 | ||||
| missense | 93 | 93 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 95 | 0 | 0 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079345.1 | 2 | MANE Select | |
| Ensembl | ENSP00000332325.4 | 2 | MANE Select | |
| Ensembl | ENSP00000807362.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| znf703 | Danio rerio | Structure: ocular blood vessel Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Generic Transcription Pathway
- RNA Polymerase II Transcription
Biological Process
- regulation of transcription, DNA-templated
- positive regulation of cell population proliferation
- positive regulation of epithelial to mesenchymal transition
- regulation of transforming growth factor beta receptor signaling pathway
- positive regulation of cell migration
Molecular Function
- nucleic acid binding
- protein binding
- metal ion binding
- repressing transcription factor binding
Cellular Component
- nucleus
- cytoplasm
- nuclear matrix
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000331569
- Coding exons
- 2
- Length
- 4269
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.08 | 172 | 268 | 0.642 | 0.0000144 | 3587 |
| Missense (PolyPhen) | 45 | 85.411 | 0.52687 | 1067 | ||
| Synonymous | 1.66 | 113 | 138 | 0.820 | 0.00000862 | 1364 |
| Loss of Function | 2.13 | 2 | 8.84 | 0.226 | 3.77e-7 | 144 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional corepressor which does not bind directly to DNA and may regulate transcription through recruitment of histone deacetylases to gene promoters. Regulates cell adhesion, migration and proliferation. May be required for segmental gene expression during hindbrain development. {ECO:0000269|PubMed:21328542, ECO:0000269|PubMed:21337521}.;
- Disease
- DISEASE: Note=Luminal B breast cancers are the clinically more aggressive estrogen receptor-positive tumors. Amplification of a distal 8p12 locus occurs in around one third of the cases and ZNF703 is the single gene within the minimal amplicon. Amplification of the gene correlates with its protein expression in tumor cells. ZNF703 is a classical breast cancer oncogene since it is able to transform non-malignant cells and increase cellular proliferation.;
Recessive Scores
- pRec
- 0.122
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |