EXO1

Chr 1

exonuclease 1

Also known as: HEX1, hExoI

NCBI Gene: 9156ENSG00000174371UniProt: Q9UQ84OMIM: 606063

This gene encodes a protein with 5' to 3' exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.93
Clinical Summary— EXO1
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Gene-Disease Validity (ClinGen)
Lynch syndrome · ADRefuted

Refuted — evidence has disproved this relationship

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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
1 unique Pathogenic / Likely Pathogenic· 88 VUS of 152 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.93LOEUF
pLI 0.000
Z-score 1.92
OE 0.66 (0.48–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-1.03Z-score
OE missense 1.14 (1.06–1.23)
500 obs / 439.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.66 (0.48–0.93)
0≤0.351.4
Missense OE?1.14 (1.06–1.23)
0≤0.61.4
Synonymous OE?1.08
0≤1.21.6
LoF obs/exp: 25 / 37.7Missense obs/exp: 500 / 439.1Syn Z: -0.86

This gene — mechanism propensity

DN
0.6937th %ile
GOF
0.3788th %ile
LOF
0.4332th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

152 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1
VUS88
Likely Benign24
Benign16
Conflicting2
1
Likely Pathogenic
88
VUS
24
Likely Benign
16
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
1
0
0
0
1
VUS
1
87
0
0
88
Likely Benign
0
10
3
11
24
Benign
0
14
1
1
16
Conflicting
—2
Total2111412131

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

View in ClinVar →

68 pathogenic / likely-pathogenic (of 92) ClinVar copy-number / structural variants overlap EXO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

EXO1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients