MUTYH

Chr 1AR

mutY DNA glycosylase

Also known as: MYH

NCBI Gene: 4595ENSG00000132781UniProt: Q9UIF7

This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

Primary Disease Associations & Inheritance

Adenomas, multiple colorectalMIM #608456
AR
Gastric cancer, somaticMIM #613659
UniProtFamilial adenomatous polyposis 2
4206
ClinVar variants
17
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— MUTYH
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 414 VUS of 4206 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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.19LOEUF
pLI 0.000
Z-score 0.66
OE 0.88 (0.66–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.21Z-score
OE missense 1.03 (0.94–1.13)
322 obs / 311.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.66–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.94–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 30 / 34.2Missense obs/exp: 322 / 311.7Syn Z: -0.13

ClinVar Variant Classifications

4206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic4
VUS414
Likely Benign56
Benign3
13
Pathogenic
4
Likely Pathogenic
414
VUS
56
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
2
0
13
Likely Pathogenic
3
0
1
0
4
VUS
0
404
10
0
414
Likely Benign
1
8
36
11
56
Benign
0
1
2
0
3
Total154135111490

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

View in ClinVar →

Protein Context — Lollipop Plot

MUTYH · protein map & ClinVar variants

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

Gene2Phenotype Curations

MUTYH-related adenomas, multiple colorectal

definitive
ARLoss Of FunctionAbsent Gene Product
Cancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Adenomas, multiple colorectal

MIM #608456

Molecular basis of disorder known

Autosomal recessive

Gastric cancer, somatic

MIM #613659

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.
Guindalini RSC et al.·Sci Rep
2022Cohort
Whole-genome landscape of pancreatic neuroendocrine tumours.
Scarpa A et al.·Nature
2017
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.
Yurgelun MB et al.·Gastroenterology
2015Cohort
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S et al.·Am J Gastroenterol
2015Review
The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients.
de Oliveira JM et al.·Eur J Hum Genet
2022Cohort
Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.
Yurgelun MB et al.·J Clin Oncol
2017
The germline mutational landscape of genitourinary cancers and its indication for prognosis and risk.
Yang Y et al.·BMC Urol
2022
Familial adenomatous polyposis.
Half E et al.·Orphanet J Rare Dis
2009Review
Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.
Zaffaroni G et al.·Br J Surg
2024Guideline
Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls.
Akcay IM et al.·Int J Cancer
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Lynch SyndromeLi Fraumeni SyndromePTEN Hamartoma Syndrome

Video Capsule Examination in Patients With Lynch Syndrome

RECRUITING
NCT06712095Phase NARoyal Marsden NHS Foundation TrustStarted 2024-03-04
Video capsule investigation
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

External Resources

Links to major genomics databases and tools