EXO5

Chr 1

exonuclease 5

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

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.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.43
Clinical SummaryEXO5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 63 VUS of 92 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.000
Z-score 0.59
OE 0.80 (0.471.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.95Z-score
OE missense 0.81 (0.710.92)
154 obs / 191.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.471.43)
00.351.4
Missense OE0.81 (0.710.92)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 8 / 10.0Missense obs/exp: 154 / 191.0Syn Z: 1.42

ClinVar Variant Classifications

92 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS63
Likely Benign5
Benign13
7
Pathogenic
2
Likely Pathogenic
63
VUS
5
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
56
7
0
63
Likely Benign
1
2
0
2
5
Benign
2
5
3
3
13
Total36319590

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

View in ClinVar →

Protein Context — Lollipop Plot

EXO5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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