ZKSCAN3
protein-codingzinc finger with KRAB and SCAN domains 3, the group of SCAN domain containing|Zinc fingers C2H2-type
Gene summary
Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Involved in several processes, including lysosome organization; negative regulation of cellular senescence; and regulation of DNA-templated transcription. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
- ZNF306
- ZNF309
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.2 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 ZKSCAN3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024493.4. 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 | 51 | 3 | 54 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 53 | 3 | 0 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_077819.2 | 5 | MANE Select | |
| Ensembl | ENSP00000252211.2 | 5 | MANE Select | |
| RefSeq | NP_001229823.1 | 5 | Standard | |
| RefSeq | NP_001229824.1 | 4 | Standard |
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
- negative regulation of transcription by RNA polymerase II
- autophagy
- lysosome organization
- negative regulation of autophagy
- negative regulation of transcription, DNA-templated
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA binding
- chromatin binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377255
- Coding exons
- 5
- Length
- 19257
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 48
- Defined
- 125747
- p
- 0.000191
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.64 | 212 | 291 | 0.730 | 0.0000151 | 3539 |
| Missense (PolyPhen) | 70 | 94.945 | 0.73727 | 1174 | ||
| Synonymous | 1.11 | 100 | 115 | 0.869 | 0.00000621 | 1012 |
| Loss of Function | 0.844 | 19 | 23.4 | 0.812 | 0.00000136 | 267 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00039 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional factor that binds to the consensus sequence 5'-[GT][AG][AGT]GGGG-3' and acts as a repressor of autophagy. Specifically represses expression of genes involved in autophagy and lysosome biogenesis/function such as MAP1LC3B, ULK1 or WIPI2. Associates with chromatin at the ITGB4 and VEGF promoters. Also acts as a transcription activator and promotes cancer cell progression and/or migration in various tumors and myelomas. {ECO:0000269|PubMed:18940803, ECO:0000269|PubMed:21057542, ECO:0000269|PubMed:22531714, ECO:0000269|PubMed:23434374}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.667
- RVIS EVS
- 0.51
- RVIS percentile EVS
- 80.1
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.629
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |