EXO1

Chr 1

exonuclease 1

Also known as: HEX1, hExoI

NCBI Gene: 9156 ENSG00000174371 UniProt: Q9UQ84 OMIM: 606063

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

Lynch syndrome · ADRefutedevidence has disproved this relationship

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.93

LOEUF

Mechanism· predicted

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING

NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14

SunitinibTemsirolimusTrastuzumab and Pertuzumab

Solid TumorAdvanced Solid TumorMetastatic Cancer

KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II

RECRUITING

NCT05525858Seoul National University Bundang HospitalStarted 2022-09-28

AlectinibAtezolizumabErlotinib

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions