RAD1

RAD1 checkpoint DNA exonuclease, the group of Checkpoint clamp complex

Basic information

Region (hg38): 5:34905260-34918989

Links

ENSG00000113456 ∙ NCBI:5810 ∙ OMIM:603153 ∙ HGNC:9806 ∙ Uniprot:O60671 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAD1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAD1 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		3
missense			18	1	3	22
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	1	2
Total	0	0	19	5	4

Variants in RAD1

This is a list of pathogenic ClinVar variants found in the RAD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-34908772-T-C		RAD1-related disorder	Benign (Nov 16, 2019)
5-34908815-C-G		RAD1-related disorder • not specified	Uncertain significance (Mar 18, 2024)
5-34908824-T-C		not specified	Uncertain significance (Dec 16, 2021)
5-34908831-A-G			Likely benign (Jul 23, 2018)
5-34908884-G-A		not specified	Uncertain significance (Nov 21, 2023)
5-34908937-G-A		not specified	Uncertain significance (May 20, 2024)
5-34908957-G-C		RAD1-related disorder	Benign (Oct 30, 2019)
5-34908957-GA-G		RAD1-related disorder	Likely benign (Dec 20, 2022)
5-34909315-T-C		RAD1-related disorder	Likely benign (Jun 02, 2022)
5-34909316-A-C		not specified	Uncertain significance (May 17, 2023)
5-34911569-T-A		not specified	Uncertain significance (Jul 09, 2021)
5-34911599-C-T		not specified	Uncertain significance (Oct 26, 2022)
5-34911601-C-T		RAD1-related disorder	Likely benign (Jun 10, 2022)
5-34911602-G-C		not specified	Uncertain significance (Feb 27, 2023)
5-34911629-C-T		not specified	Uncertain significance (Apr 04, 2023)
5-34911633-G-C		not specified	Uncertain significance (Dec 22, 2023)
5-34911653-A-G		RAD1-related disorder	Uncertain significance (Jul 11, 2023)
5-34911698-T-C		not specified	Uncertain significance (Jul 09, 2021)
5-34911717-T-G		not specified	Uncertain significance (Aug 02, 2023)
5-34911746-T-C		not specified	Uncertain significance (Aug 13, 2021)
5-34911767-G-C		RAD1-related disorder	Uncertain significance (Mar 09, 2024)
5-34911779-C-T		RAD1-related disorder	Benign (Nov 04, 2019)
5-34911794-C-T		RAD1-related disorder	Uncertain significance (May 26, 2023)
5-34911795-G-A		RAD1-related disorder	Uncertain significance (Jul 12, 2023)
5-34911809-G-C		RAD1-related disorder	Benign (Nov 08, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAD1	protein_coding	protein_coding	ENST00000382038	5	13726

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000123	0.850	125599	0	149	125748	0.000593

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.270	136	145	0.937	0.00000674	1854
Missense in Polyphen		38	48.922	0.77675		651
Synonymous	1.05	42	51.6	0.814	0.00000232	527
Loss of Function	1.32	8	13.2	0.607	6.89e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000706	0.000706
Ashkenazi Jewish	0.00	0.00
East Asian	0.000179	0.000163
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.00109	0.00109
Middle Eastern	0.000179	0.000163
South Asian	0.000200	0.000196
Other	0.000495	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10846170, PubMed:10884395). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:12578958). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:15871698). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:15314187, PubMed:15556996, PubMed:15871698). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). Isoform 1 possesses 3'->5' double stranded DNA exonuclease activity (PubMed:9660799). {ECO:0000269|PubMed:10846170, ECO:0000269|PubMed:10884395, ECO:0000269|PubMed:12578958, ECO:0000269|PubMed:15314187, ECO:0000269|PubMed:15556996, ECO:0000269|PubMed:15871698, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:9660799}.
• Pathway: Cellular senescence - Homo sapiens (human);miRNA Regulation of DNA Damage Response;ATR Signaling;DNA Damage Response;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;role of brca1 brca2 and atr in cancer susceptibility;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Regulation of Telomerase;Processing of DNA double-strand break ends;ATR signaling pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.844
• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.383
• hipred: Y
• hipred_score: 0.675
• ghis: 0.597

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rad1
• Phenotype: skeleton 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: DNA damage checkpoint;DNA repair;cellular response to DNA damage stimulus;substantia nigra development;meiotic recombination checkpoint;cellular response to ionizing radiation;nucleic acid phosphodiester bond hydrolysis
• Cellular component: nucleus;nucleoplasm;chromosome;checkpoint clamp complex;intracellular membrane-bounded organelle
• Molecular function: damaged DNA binding;protein binding;3'-5' exonuclease activity;exodeoxyribonuclease III activity