GCFC2
protein-codingGC-rich sequence DNA-binding factor 2
Gene summary
The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in the cloning process (see Genbank accession M29204). A positively charged amino terminus present only in the chimera was determined to bind GC-rich DNA, thus mistakenly thought to identify a transcription factor gene. [provided by RefSeq, Jul 2008]
- TCF9
- C2orf3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.0 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 GCFC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003203.5. 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 | 97 | 11 | 1 | 109 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 101 | 12 | 1 | 114 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003194.3 | 17 | MANE Select | |
| Ensembl | ENSP00000318690.3 | 17 | MANE Select | |
| RefSeq | NP_001188263.1 | 15 | Standard | |
| RefSeq | NP_001188264.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- spliceosomal complex assembly
- mRNA splicing, via spliceosome
- regulation of transcription, DNA-templated
- negative regulation of transcription, DNA-templated
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytosol
- U2-type post-mRNA release spliceosomal complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000321027
- Coding exons
- 17
- Length
- 58990
- Individuals with no LoFs
- 125470
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 276
- Defined
- 125748
- p
- 0.00111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.00392 | 377 | 377 | 0.999 | 0.0000178 | 5115 |
| Missense (PolyPhen) | 94 | 100.66 | 0.93386 | 1388 | ||
| Synonymous | -1.49 | 154 | 132 | 1.16 | 0.00000624 | 1398 |
| Loss of Function | 0.655 | 39 | 43.7 | 0.893 | 0.00000228 | 543 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00078 | 0.00074 | rare |
| Latino/Admixed American | 0.0014 | 0.0012 | notable |
| Ashkenazi Jewish | 0.00084 | 0.00069 | rare |
| East Asian | 0.0015 | 0.0014 | notable |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.0023 | 0.0021 | notable |
| Other | 0.00071 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Factor that represses transcription. It binds to the GC- rich sequences (5'-GCGGGGC-3') present in the epidermal growth factor receptor, beta-actin, and calcium-dependent protease promoters. Involved in pre-mRNA splicing through regulating spliceosome C complex formation. May play a role during late-stage splicing events and turnover of excised inrons. {ECO:0000269|PubMed:24304693}.;
Recessive Scores
- pRec
- 0.189
Intolerance Scores
- RVIS EVS
- 1.51
- RVIS percentile EVS
- 95.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |