EXO5

protein-coding

exonuclease 5, the group of Exonucleases

Gene summary

The protein encoded by this gene is a single-stranded DNA (ssDNA)-specific exonuclease that can slide along the DNA before cutting it. However, human replication protein A binds ssDNA and restricts sliding of the encoded protein, providing a 5'-directionality to the enzyme. This protein localizes to nuclear repair loci after DNA damage. [provided by RefSeq, Nov 2016]

Previous symbols:

C1orf176
DEM1

MANE transcript

NM_001346953.2

Inheritance

—

ClinVar variants

U:58B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr1:40,508,741-40,516,038

External References & Databases

Ensembl (ENSG00000164002)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 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 EXO5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 15

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001346953.2. 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	2 clinvar	2 clinvar	5
missense			56 clinvar	2 clinvar	2 clinvar	60
nonsense						0
start loss						0
frameshift				1 clinvar	2 clinvar	3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	58	5	6	69

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 86 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001346953.2	RefSeq	NP_001333882.1	1	MANE Select
ENST00000415550.6	Ensembl	ENSP00000413565.2	1	MANE Select
NM_001346946.2	RefSeq	NP_001333875.1	1	Standard
NM_001346947.2	RefSeq	NP_001333876.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

interstrand cross-link repair
nucleic acid phosphodiester bond hydrolysis

Molecular Function

DNA binding
single-stranded DNA 3'-5' exodeoxyribonuclease activity
protein homodimerization activity
single-stranded DNA 5'-3' exodeoxyribonuclease activity
metal ion binding

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372703
Coding exons: 1
Length: 7816
Individuals with no LoFs: 122990
Homozygous LoFs: 206
Heterozygous LoFs: 2551
Defined: 125747
p: 0.0110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.951	154	191	0.806	0.00000923	2409
Missense (PolyPhen)		43	65.531	0.65618		877
Synonymous	1.42	59	74.6	0.790	0.00000345	762
Loss of Function	0.592	8	10.0	0.798	5.11e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0078	0.0078	notable
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.15	0.15	notable
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00035	0.00035	rare
South Asian	0.0016	0.0016	notable
Other	0.0047	0.0047	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Single-stranded DNA (ssDNA) bidirectional exonuclease involved in DNA repair. Probably involved in DNA repair following ultraviolet (UV) irradiation and interstrand cross-links (ICLs) damage. Has both 5'-3' and 3'-5' exonuclease activities with a strong preference for 5'-ends. Acts as a sliding exonuclease that loads at ssDNA ends and then slides along the ssDNA prior to cutting; however the sliding and the 3'-5' exonuclease activities are abolished upon binding to the replication protein A (RPA) complex that enforces 5'-directionality activity. {ECO:0000269|PubMed:23095756}.;

Intolerance Scores

RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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