RFC1

replication factor C subunit 1, the group of AAA ATPases

Basic information

Region (hg38): 4:39287455-39366375

Links

ENSG00000035928 ∙ NCBI:5981 ∙ OMIM:102579 ∙ HGNC:9969 ∙ Uniprot:P35251 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (Moderate), mode of inheritance: AR
• cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (Supportive), mode of inheritance: AR
• cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	30926972; 32851396

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RFC1 gene.

• Inborn genetic diseases (49 variants)
• not provided (10 variants)
• Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (6 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense			50	3	3	56
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					3	3
Total	0	1	50	6	7

Variants in RFC1

This is a list of pathogenic ClinVar variants found in the RFC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-39288763-A-T			Uncertain significance (May 01, 2023)
4-39288823-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
4-39288842-T-C		RFC1-related disorder	Benign (Nov 07, 2019)
4-39289874-C-G		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
4-39289933-G-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
4-39291682-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
4-39291745-A-G		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
4-39291770-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
4-39291791-C-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
4-39291794-G-A		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
4-39291812-A-C		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
4-39291824-T-C		Inborn genetic diseases	Uncertain significance (May 23, 2023)
4-39295632-G-A		Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome	Uncertain significance (Apr 04, 2024)
4-39295650-C-T		Inborn genetic diseases	Uncertain significance (Mar 24, 2023)
4-39295708-G-T		RFC1-related disorder	Benign (Dec 31, 2019)
4-39295714-T-G		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
4-39299985-G-C		Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome	Benign (Nov 07, 2021)
4-39300056-G-A		Inborn genetic diseases	Uncertain significance (Oct 18, 2021)
4-39300259-C-T		Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome	Pathogenic (Aug 28, 2023)
4-39300326-T-C		Inborn genetic diseases	Uncertain significance (May 03, 2023)
4-39300335-A-G		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
4-39300409-T-C		Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome • RFC1-related disorder	Benign (Nov 07, 2021)
4-39302276-A-G		Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome	Pathogenic (Aug 28, 2023)
4-39302305-A-G		RFC1-related disorder	Benign (Oct 30, 2019)
4-39302312-G-C		Inborn genetic diseases	Uncertain significance (May 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RFC1	protein_coding	protein_coding	ENST00000381897	25	78920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0270	125628	2	117	125747	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	502	597	0.841	0.0000305	7589
Missense in Polyphen		101	172.06	0.58699		2103
Synonymous	-0.115	211	209	1.01	0.0000111	2063
Loss of Function	5.84	11	59.6	0.184	0.00000301	809

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000170	0.000167
Middle Eastern	0.0000544	0.0000544
South Asian	0.00317	0.00311
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins PCNA and activator 1. This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Could play a role in DNA transcription regulation as well as DNA replication and/or repair. Can bind single- or double-stranded DNA. {ECO:0000269|PubMed:8999859}.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Nucleotide Excision Repair ;miRNA Regulation of DNA Damage Response;DNA Replication;Mismatch repair;DNA Damage Response;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;alk in cardiac myocytes;Homology Directed Repair;Polymerase switching on the C-strand of the telomere;DNA Replication;Polymerase switching;Leading Strand Synthesis;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Recognition of DNA damage by PCNA-containing replication complex;Translesion synthesis by REV1;Translesion Synthesis by POLH;Translesion synthesis by POLK;Translesion synthesis by POLI;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;FAS (CD95) signaling pathway;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.319

Intolerance Scores

• loftool: 0.581
• rvis_EVS: -0.95
• rvis_percentile_EVS: 9.38

Haploinsufficiency Scores

• pHI: 0.921
• hipred: Y
• hipred_score: 0.635
• ghis: 0.644

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.886

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rfc1
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;DNA-dependent DNA replication;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, DNA gap filling;telomere maintenance via telomerase;translesion synthesis;telomere maintenance via semi-conservative replication;nucleotide-excision repair, DNA incision;error-prone translesion synthesis;DNA damage response, detection of DNA damage;positive regulation of catalytic activity;positive regulation of transcription, DNA-templated;error-free translesion synthesis;DNA clamp unloading
• Cellular component: nucleus;nucleoplasm;DNA replication factor C complex;nucleolus;cytoplasm;Elg1 RFC-like complex;extracellular exosome
• Molecular function: DNA binding;DNA clamp loader activity;double-stranded DNA binding;protein binding;ATP binding;enzyme activator activity;protein domain specific binding;sequence-specific DNA binding;DNA clamp unloader activity