RFC3
protein-codingreplication factor C subunit 3, the group of AAA ATPases
Gene summary
The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kDa. This gene encodes the 38 kDa subunit. This subunit is essential for the interaction between the 140 kDa subunit and the core complex that consists of the 36, 37, and 40 kDa subunits. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~148.5 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 RFC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002915.4. 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 | 1 | 1 | ||||
| missense | 44 | 44 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 45 | 0 | 0 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002906.1 | 9 | MANE Select | |
| Ensembl | ENSP00000369411.3 | 9 | MANE Select | |
| RefSeq | NP_853536.2 | 9 | Standard | |
| Ensembl | ENSP00000401001.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nucleotide excision repair - Homo sapiens (human)
- Mismatch repair - Homo sapiens (human)
- DNA replication - Homo sapiens (human)
- Gastric Cancer Network 2
- Retinoblastoma (RB) in Cancer
Biological Process
- DNA synthesis involved in DNA repair
- DNA replication
- DNA-dependent DNA replication
- DNA strand elongation involved in DNA replication
- transcription-coupled nucleotide-excision repair
Molecular Function
- DNA binding
- DNA clamp loader activity
- protein binding
- ATPase activity
- single-stranded DNA-dependent ATPase activity
Cellular Component
- nucleus
- nucleoplasm
- DNA replication factor C complex
- Ctf18 RFC-like complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380071
- Coding exons
- 9
- Length
- 148510
- Individuals with no LoFs
- 125700
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 48
- Defined
- 125748
- p
- 0.000191
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.128 | 196 | 191 | 1.03 | 0.00000946 | 2324 |
| Missense (PolyPhen) | 71 | 73.433 | 0.96687 | 870 | ||
| Synonymous | -0.135 | 66 | 64.6 | 1.02 | 0.00000316 | 663 |
| Loss of Function | 1.75 | 11 | 19.3 | 0.569 | 9.80e-7 | 243 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00013 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00028 | 0.00027 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1.;
Recessive Scores
- pRec
- 0.277
Intolerance Scores
- LoFtool
- 0.862
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.31
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |