EXO5

Chr 1

exonuclease 5

Also known as: C1orf176, DEM1, Exo V, hExo5

NCBI Gene: 64789 ENSG00000164002 UniProt: Q9H790

The protein is a single-stranded DNA exonuclease that slides along DNA before cutting it and localizes to nuclear repair sites after DNA damage, functioning in DNA repair following ultraviolet irradiation and interstrand cross-link damage. Mutations cause autosomal recessive EXO5-related disorder, characterized by developmental delay, intellectual disability, and microcephaly with onset in infancy or early childhood. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed clinically.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 1.43

Clinical Summary— EXO5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

56 VUS of 76 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.59

OE 0.80 (0.47–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.95Z-score

OE missense 0.81 (0.71–0.92)

154 obs / 191.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.47–1.43)

0≤0.351.4

Missense OE?0.81 (0.71–0.92)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 8 / 10.0Missense obs/exp: 154 / 191.0Syn Z: 1.42

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

VUS56

Likely Benign5

Benign13

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	56	0	0	56
Likely Benign	1	2	0	2	5
Benign	2	5	3	3	13
Total	3	63	3	5	74

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap EXO5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →