ZC3H8
protein-codingzinc finger CCCH-type containing 8, the group of Zinc fingers CCCH-type
Gene summary
Enables RNA binding activity. Involved in several processes, including positive regulation of thymocyte apoptotic process; regulation of DNA-templated transcription; and snRNA transcription. Located in Cajal body; euchromatin; and histone locus body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Jul 2025]
- ZC3HDC8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.6 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 ZC3H8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032494.3. 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 | 0 | |||||
| missense | 24 | 2 | 2 | 28 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 27 | 2 | 2 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115883.2 | 8 | MANE Select | |
| Ensembl | ENSP00000386488.1 | 8 | MANE Select | |
| Ensembl | ENSP00000536758.1 | 7 | Standard | |
| Ensembl | ENSP00000536758.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- RNA polymerase II transcribes snRNA genes
- RNA Polymerase II Transcription
Biological Process
- negative regulation of transcription by RNA polymerase II
- apoptotic process
- negative regulation of T cell differentiation in thymus
- snRNA transcription by RNA polymerase II
- snRNA transcription by RNA polymerase III
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- RNA binding
Cellular Component
- nucleus
- nucleoplasm
- transcription elongation factor complex
- Cajal body
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409573
- Coding exons
- 8
- Length
- 43612
- Individuals with no LoFs
- 124625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 124638
- p
- 0.0000522
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 88 | 133 | 0.662 | 0.00000615 | 1935 |
| Missense (PolyPhen) | 16 | 41.616 | 0.38446 | 647 | ||
| Synonymous | 0.846 | 39 | 46.3 | 0.842 | 0.00000232 | 462 |
| Loss of Function | 2.83 | 4 | 16.4 | 0.245 | 7.70e-7 | 243 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000066 | 0.000065 | rare |
| Latino/Admixed American | 0.00014 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a transcriptional repressor of the GATA3 promoter. Sequence-specific DNA-binding factor that binds to the 5'-AGGTCTC-3' sequence within the negative cis-acting element intronic regulatory region (IRR) of the GATA3 gene (By similarity). Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:23932780). Induces thymocyte apoptosis when overexpressed, which may indicate a role in regulation of thymocyte homeostasis. {ECO:0000250, ECO:0000269|PubMed:12077251, ECO:0000269|PubMed:12153508, ECO:0000269|PubMed:23932780}.;
Intolerance Scores
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 67.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.355
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |