ZC3H3
protein-codingzinc finger CCCH-type containing 3, the group of Zinc fingers CCCH-type
Gene summary
Predicted to enable DNA binding activity; R-SMAD binding activity; and zinc ion binding activity. Predicted to be involved in RNA catabolic process. Predicted to act upstream of or within mRNA 3'-end processing and positive regulation of activin receptor signaling pathway. Located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
- ZC3HDC3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~103.8 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 ZC3H3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015117.3. 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 | 4 | 5 | |||
| missense | 204 | 23 | 1 | 228 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 208 | 27 | 1 | 236 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055932.2 | 12 | MANE Select | |
| Ensembl | ENSP00000262577.5 | 12 | MANE Select | |
| Ensembl | ENSP00000436834.1 | 2 | Standard | |
| Ensembl | ENSP00000545825.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- mRNA polyadenylation
- regulation of mRNA export from nucleus
- poly(A)+ mRNA export from nucleus
- positive regulation of activin receptor signaling pathway
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- molecular_function
- DNA binding
- metal ion binding
- R-SMAD binding
Cellular Component
- nucleus
- mRNA cleavage and polyadenylation specificity factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262577
- Coding exons
- 12
- Length
- 103799
- Individuals with no LoFs
- 125685
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125712
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00625 | 592 | 592 | 1.00 | 0.0000400 | 5928 |
| Missense (PolyPhen) | 162 | 186.27 | 0.8697 | 1755 | ||
| Synonymous | -2.88 | 314 | 255 | 1.23 | 0.0000171 | 2113 |
| Loss of Function | 4.10 | 7 | 32.1 | 0.218 | 0.00000152 | 402 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00034 | 0.00031 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.000091 | 0.000088 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for the export of polyadenylated mRNAs from the nucleus (PubMed:19364924). Enhances ACVR1B-induced SMAD-dependent transcription. Binds to single-stranded DNA but not to double- stranded DNA in vitro. Involved in RNA cleavage (By similarity). {ECO:0000250|UniProtKB:Q8CHP0, ECO:0000269|PubMed:19364924}.;
Recessive Scores
- pRec
- 0.0960
Intolerance Scores
- LoFtool
- 0.485
- RVIS EVS
- 2.68
- RVIS percentile EVS
- 98.86
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- N
- Indispensability score
- 0.197
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |