RAD17

protein-coding

RAD17 checkpoint clamp loader component

Gene summary

The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified. [provided by RefSeq, Jul 2013]

MANE transcript

NM_133338.3

Inheritance

—

ClinVar variants

U:101B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr5:69,369,293-69,414,801

External References & Databases

Ensembl (ENSG00000152942)

Transcript & Mutation Effects

hg38 • Region Span ~45.5 kb

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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 RAD17 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 90

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133338.3. 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	1 clinvar		2
missense			91 clinvar	2 clinvar		93
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	101	3	0	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 121 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133338.3	RefSeq	NP_579916.1	16	MANE Select
ENST00000354868.10	Ensembl	ENSP00000346938.5	16	MANE Select
NM_001278622.1	RefSeq	NP_001265551.1	16	Standard
NM_002873.1	RefSeq	NP_002864.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miRNA Regulation of DNA Damage Response
Gastric Cancer Network 2
DNA Damage Response
HDR through Single Strand Annealing (SSA)
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)

Biological Process

DNA replication checkpoint
DNA damage checkpoint
DNA replication
DNA repair
cellular response to DNA damage stimulus

Molecular Function

chromatin binding
DNA clamp loader activity
protein binding
ATP binding

Cellular Component

chromosome, telomeric region
nuclear chromatin
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000509734
Coding exons: 16
Length: 45509
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.618	310	342	0.906	0.0000167	4443
Missense (PolyPhen)		60	86.614	0.69273		1193
Synonymous	-0.00516	120	120	1.00	0.00000595	1268
Loss of Function	4.22	10	38.1	0.262	0.00000207	490

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000066	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the RAD1-RAD9- HUS1 complex and RHNO1 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination. {ECO:0000269|PubMed:10208430, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:12578958, ECO:0000269|PubMed:12672690, ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:14624239, ECO:0000269|PubMed:15235112, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:21659603}.;

Recessive Scores

pRec: 0.207

Intolerance Scores

LoFtool: 0.936
RVIS EVS: -0.07
RVIS percentile EVS: 48.78

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.581

Gene Damage Prediction

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