MUTYH

Chr 1AR

mutY DNA glycosylase

Also known as: MYH

This DNA glycosylase removes inappropriately paired adenine bases from oxidative DNA damage sites, particularly adenine paired with 8-oxoguanine lesions. Biallelic mutations cause MUTYH-associated polyposis (MAP), characterized by multiple colorectal adenomas and increased risk of colorectal and gastric cancer, following autosomal recessive inheritance. The gene shows high tolerance to loss-of-function variants (LOEUF 1.19), suggesting the recessive phenotype requires complete loss of function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.192 OMIM phenotypes
Clinical SummaryMUTYH
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Gene-Disease Validity (ClinGen)
familial ovarian cancer · ARDisputed

Disputed — evidence questions this relationship

6 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 402 VUS of 500 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MUTYH
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.000
Z-score 0.66
OE 0.88 (0.661.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.21Z-score
OE missense 1.03 (0.941.13)
322 obs / 311.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.88 (0.661.19)
00.351.4
Missense OE1.03 (0.941.13)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 30 / 34.2Missense obs/exp: 322 / 311.7Syn Z: -0.13

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic6
VUS402
Likely Benign64
Benign4
14
Pathogenic
6
Likely Pathogenic
402
VUS
64
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
1
0
14
Likely Pathogenic
5
1
0
0
6
VUS
1
391
10
0
402
Likely Benign
1
10
37
16
64
Benign
0
2
2
0
4
Total204045016490

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →