EXO1

Chr 1

exonuclease 1

Also known as: HEX1, hExoI

This gene encodes a 5' to 3' exonuclease that functions in DNA mismatch repair, somatic hypermutation of immunoglobulin genes, and is essential for meiosis. Mutations cause autosomal recessive endometrial cancer predisposition and are associated with hereditary nonpolyposis colorectal cancer susceptibility. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.93
Clinical SummaryEXO1
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Gene-Disease Validity (ClinGen)
Lynch syndrome · ADRefuted

Refuted — evidence has disproved this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.92
OE 0.66 (0.480.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.03Z-score
OE missense 1.14 (1.061.23)
500 obs / 439.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.480.93)
00.351.4
Missense OE1.14 (1.061.23)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 25 / 37.7Missense obs/exp: 500 / 439.1Syn Z: -0.86
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EXO1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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