RFC2

protein-coding

replication factor C subunit 2, the group of AAA ATPases

Gene summary

This gene encodes a member of the activator 1 small subunits family. 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 replication factor C (RFC). Replication factor C, also called activator 1, is a protein complex consisting of five distinct subunits. This gene encodes the 40 kD subunit, which has been shown to be responsible for binding ATP and may help promote cell survival. Disruption of this gene is associated with Williams syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene of this gene has been defined on chromosome 2. [provided by RefSeq, Jul 2013]

MANE transcript

NM_181471.3

Inheritance

—

ClinVar variants

U:45B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr7:74,231,499-74,254,458

External References & Databases

Ensembl (ENSG00000049541)

Transcript & Mutation Effects

hg38 • Region Span ~23.0 kb

Loading mutation effect viewer...

GenCC 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 RFC2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 39

not providedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181471.3. 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 clinvar	13 clinvar	4 clinvar	18
missense			39 clinvar	3 clinvar	1 clinvar	43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	45	16	5	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181471.3	RefSeq	NP_852136.1	11	MANE Select
ENST00000055077.8	Ensembl	ENSP00000055077.3	11	MANE Select
NM_001278791.2	RefSeq	NP_001265720.1	8	Standard
NM_001278792.2	RefSeq	NP_001265721.1	8	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)
DNA Replication
HDR through Single Strand Annealing (SSA)

Biological Process

DNA replication
DNA-dependent DNA replication
transcription-coupled nucleotide-excision repair
nucleotide-excision repair, DNA incision, 5'-to lesion
nucleotide-excision repair, DNA gap filling

Molecular Function

DNA clamp loader activity
protein binding
ATP binding
enzyme binding
single-stranded DNA-dependent ATPase activity

Cellular Component

nucleus
nucleoplasm
DNA replication factor C complex
Ctf18 RFC-like complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000055077
Coding exons: 11
Length: 22946
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125748
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.15	160	207	0.774	0.0000112	2330
Missense (PolyPhen)		31	60.551	0.51196		657
Synonymous	-0.461	88	82.7	1.06	0.00000515	679
Loss of Function	1.64	12	19.9	0.603	9.96e-7	229

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00051	0.00049	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

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. This subunit binds ATP (By similarity). {ECO:0000250}.;
Disease: DISEASE: Note=RFC2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region (PubMed:11003705). {ECO:0000269|PubMed:11003705}.;

Recessive Scores

pRec: 0.339

Intolerance Scores

LoFtool: 0.510
RVIS EVS: -0.56
RVIS percentile EVS: 19.54

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.936

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium