EXO1

Chr 1

exonuclease 1

Also known as: HEX1, hExoI

NCBI Gene: 9156 ENSG00000174371 UniProt: Q9UQ84

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]

Active trials

Pathogenic / LP

222

ClinVar variants

Pubs (1 yr)

-1.0

Missense Z

0.93

LOEUF

Clinical Summary— EXO1

🧬

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.

📋

ClinVar Variants

69 Pathogenic / Likely Pathogenic· 108 VUS of 222 total submissions

💊

Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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 OE0.66 (0.48–0.93)

0≤0.351.4

Missense OE1.14 (1.06–1.23)

0≤0.61.4

Synonymous OE1.08

0≤1.21.6

LoF obs/exp: 25 / 37.7Missense obs/exp: 500 / 439.1Syn Z: -0.86

Badonyi & Marsh 2024 ↗

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

222 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64

Likely Pathogenic5

VUS108

Likely Benign26

Benign17

Conflicting2

Pathogenic

Likely Pathogenic

108

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	64	0	64
Likely Pathogenic	0	0	5	0	5
VUS	1	87	20	0	108
Likely Benign	0	10	5	11	26
Benign	0	15	1	1	17
Conflicting	—				2
Total	1	112	95	12	222

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

View in ClinVar →

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

PalbociclibSunitinibTemsirolimus

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

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3