ZNF683
protein-codingzinc finger protein 683, the group of Zinc fingers C2H2-type
Gene summary
Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in T cell receptor signaling pathway; cellular response to ionomycin; and regulation of gene expression. Predicted to be located in nucleus. [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 ~12.9 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 ZNF683 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001114759.3. 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 | 2 | 3 | |||
| missense | 81 | 6 | 87 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 85 | 8 | 0 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001108231.1 | 5 | MANE Select | |
| Ensembl | ENSP00000344095.3 | 5 | MANE Select | |
| RefSeq | NP_001294854.1 | 6 | Standard | |
| RefSeq | NP_775845.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- adaptive immune response
- regulation of transcription by RNA polymerase II
- regulation of gene expression
- regulation of natural killer cell differentiation
- regulation of natural killer cell differentiation involved in immune response
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- metal ion binding
- promoter-specific chromatin binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374204
- Coding exons
- 5
- Length
- 12889
- Individuals with no LoFs
- 125351
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125366
- p
- 0.0000598
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.101 | 284 | 279 | 1.02 | 0.0000154 | 3233 |
| Missense (PolyPhen) | 58 | 67.625 | 0.85767 | 895 | ||
| Synonymous | 0.698 | 109 | 119 | 0.918 | 0.00000638 | 1062 |
| Loss of Function | 0.609 | 12 | 14.5 | 0.827 | 7.78e-7 | 163 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00044 | 0.00043 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000028 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T-cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs. Plays a role in the development, retention and long-term establishment of adaptive and innate tissue-resident lymphocyte T cell types in non-lymphoid organs, such as the skin and gut, but also in other nonbarrier tissues like liver and kidney, and therefore may provide immediate immunological protection against reactivating infections or viral reinfection. Plays also a role in the differentiation of both thymic and peripheral NKT cells. Negatively regulates the accumulation of interferon-gamma (IFN- gamma) in NKT cells at steady state or after antigenic stimulation. Positively regulates granzyme B production in NKT cells after innate stimulation. Associates with the transcriptional repressor PRDM1/BLIMP1 to chromatin at gene promoter regions. {ECO:0000250|UniProtKB:I7HJS4}.; FUNCTION: Isoform 2: Transcriptional repressor that binds to DNA within promoter regions of the transcriptional repressor PRDM1/BLIMP1 target sites. Regulates interferon-gamma (IFN-gamma) production in cytomegalovirus (CMV)-infected effector CD8(+) T cells. {ECO:0000269|PubMed:26179882}.;
Intolerance Scores
- LoFtool
- 0.992
- RVIS EVS
- 1.09
- RVIS percentile EVS
- 91.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.555
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |