GeneBe

MUTYH

mutY DNA glycosylase, the group of DNA glycosylases

Basic information

Region (hg38): 1:45329163-45340893

Links

ENSG00000132781 ∙ NCBI:4595 ∙ OMIM:604933 ∙ HGNC:7527 ∙ Uniprot:Q9UIF7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • familial adenomatous polyposis 2 (Strong), mode of inheritance: AR
  • familial adenomatous polyposis 2 (Supportive), mode of inheritance: AD
  • familial adenomatous polyposis 2 (Strong), mode of inheritance: AR
  • familial ovarian cancer (Disputed Evidence), mode of inheritance: AR
  • familial ovarian cancer (Disputed Evidence), mode of inheritance: AD
  • familial adenomatous polyposis 2 (Definitive), mode of inheritance: AR
  • hereditary breast carcinoma (Disputed Evidence), mode of inheritance: AR
  • colorectal cancer (Disputed Evidence), mode of inheritance: AD
  • hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Familial adenomatous polyposis, 2; Colorectal adenomatous polyposis, autosomal recessive, with pilomatricomasAROncologicIndividuals may present with colonic neoplasia, and regular surveillance for neoplasms may allow early treatment of tumors, which may improve outcomes; In some individuals, additional surgical measures such as total colectomy with ileorectal anastomosis, may be indicated in addition to surveillance for neoplasms; In addition to colorectal neoplasms, individuals are at high risk for a number of other cancer types (including breast cancer), and awareness may allow early diagnosis and treatmentDermatologic; Oncologic11818965; 12393807; 12853198; 12606733; 15690400; 21061173; 21063410; 21171015; 21696383; 22371070; 22658618; 22744763; 22851115; 22865608
Variants may also be inolved in susceptibility to other types of malignancies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MUTYH gene.

  • Familial adenomatous polyposis 2 (94 variants)
  • Hereditary cancer-predisposing syndrome (69 variants)
  • not provided (18 variants)
  • Carcinoma of colon (5 variants)
  • Gastric cancer (5 variants)
  • Gastric cancer;Familial adenomatous polyposis 2 (3 variants)
  • Familial adenomatous polyposis 2;Gastric cancer (2 variants)
  • MUTYH-related disorder (2 variants)
  • Familial colorectal cancer (2 variants)
  • Familial adenomatous polyposis 2;Pilomatrixoma;Neoplasm of stomach (1 variants)
  • not specified (1 variants)
  • Breast carcinoma (1 variants)
  • B lymphoblastic leukemia lymphoma, no ICD-O subtype (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MUTYH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
10
clinvar
477
clinvar
1
clinvar
 488
missense
3
clinvar
22
clinvar
1093
clinvar
9
clinvar
2
clinvar
 1129
nonsense
41
clinvar
32
clinvar
5
clinvar
 78
start loss
1
clinvar
1
clinvar
10
clinvar
 12
frameshift
73
clinvar
55
clinvar
7
clinvar
 135
inframe indel
1
clinvar
2
clinvar
31
clinvar
 34
splice donor/acceptor (+/-2bp)
5
clinvar
59
clinvar
5
clinvar
 69
splice region
7
101
92
3
 203
non coding
1
clinvar
54
clinvar
305
clinvar
21
clinvar
 381
Total 124 172 1215 791 24

Highest pathogenic variant AF is 0.0000656

Variants in MUTYH

This is a list of pathogenic ClinVar variants found in the MUTYH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-45329266-TAAC-T Familial adenomatous polyposis 2 • not specified Conflicting classifications of pathogenicity (Aug 15, 2023)297466
1-45329287-A-G Hereditary cancer-predisposing syndrome Uncertain significance (Jan 30, 2019)923209
1-45329287-ATGGGGGCTTTC-A not specified Likely benign (Aug 15, 2023)2575391
1-45329288-TG-T Hereditary cancer-predisposing syndrome Likely benign (Mar 23, 2017)631444
1-45329291-G-A Hereditary cancer-predisposing syndrome Likely benign (Sep 16, 2016)627723
1-45329299-A-T Hereditary cancer-predisposing syndrome Uncertain significance (Oct 08, 2019)925382
1-45329302-G-C Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 Uncertain significance (Aug 15, 2023)479982
1-45329303-G-T Hereditary cancer-predisposing syndrome Uncertain significance (Mar 16, 2017)229745
1-45329303-GTGTCACTGGGCTGCACTGTTGAGGCTGTGTGCATCAGTGGAGATGTGAGACCGAAAGAAATTATCCAGGACTTGCTGGCCCATGCGGGGCTTTTTCCGACTGCACGGAGAGGACACCTGGGACCTTTTGGAACCCTGTGAAAAAATGGAAGGAGGGAGGCCTTGTAGTTGGGGGAGGGGGAGCAGAGAATCCTCTCCTTGTCCTCTCTCCCTTTCCCCGACTCTACTGATCTAGCTAGGCTTAGCCTGGAATGCTGTAGAGCTTTCATCCTGCCTCAAGTATCTGCCCCATCAATCAACCCTCCAAAAGGCTGCCTGAGGGAATCGAATTGTCCTAAAAATGCAAATCTGACTCCTCTCTCCTCCACCTAAAATGAGTCAGCAGCCTAGGGCTCACACCCTGACTGACCCAGCAGGCCCTGCTGACCTTTCCAGCTAAACCAACTGCTCACAGCTCCTTGAGCACTGCAGCCTGCACTGGGCTCCACCTTTGCTCACACTACTCTTGGGACTGGAAAGAACATCGCTACGGTTGATTCCCCTCCCAAACCTGAAGAAAAGGATTCATTTCTAGGACGAAGATTACCAGCTGCTTCCTCCAAACAGCCTTTCCTGATCCGTCTCCCAATTAGAACTGATAGCTCCCATGGATGGGTGTGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCAAGATGGGCAGATCACTTGAGGTCAGGAGTTCGAGACCAGCCTAGTCAACATGGTGAAACCCTGTCTCTACTAAAAATACAAAAATTAGTTGGGTGTGGTAGCAGGCACCTGTAATCCCAGCTACTTGGGAGACTGAGGCAGGAGAATCGCTTTAATCCAGTTGTGGGAGATTGCAGTGAGCCGAGATCGGGCCACTGCACTCTAGCTTGGGTGACAGTGAGACTGTCTCAAAAAAAAAAAAAAAAAAAAAAAAGAACTGATGGCTCCACAATTCATATCCCACAAAACTCAGTACAGGCATTTCACACACCTGTGACACTGGAGAGTCCTCATCATTTTTTTCCTTTCCCTCTACCCTGCACCCCACAATGGAAGGTCTCCAGGTCAAGAACTATTCCTCCCTCCAGTGAAGCCTGGAGTGGAGAATGTTCACCCAGACATTCGTTAGTTAACTGACTAAAAACCTATGGACTCAGGCCTGGGGAGACACGGTTGGGAGAGGCCTAGGAGACTTACCATACAGGTCCCTGGCTGTTGGCCCTGATACACACGGAAAACCTAGACAAGAAGACAGGGAGGTGAGGGCTGGCACTTTTTGCAAAAGAGATA-G Familial adenomatous polyposis 2 Pathogenic (-)1050536
1-45329307-C-G Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 Uncertain significance (May 08, 2024)819745
1-45329309-C-T Familial adenomatous polyposis 2 Likely benign (Feb 23, 2022)2102618
1-45329309-CT-C Colorectal cancer Pathogenic (-)998147
1-45329310-T-G Familial adenomatous polyposis 2 Uncertain significance (Jan 30, 2024)2710233
1-45329310-TG-T Hereditary cancer-predisposing syndrome Likely pathogenic (Nov 19, 2020)1777140
1-45329311-G-A Familial adenomatous polyposis 2 • Hereditary cancer-predisposing syndrome Uncertain significance (Aug 30, 2022)406862
1-45329311-G-T Hereditary cancer-predisposing syndrome Uncertain significance (Feb 08, 2019)819718
1-45329312-G-A Hereditary cancer-predisposing syndrome Likely benign (Oct 12, 2022)1777110
1-45329312-G-T Familial adenomatous polyposis 2 Likely benign (Mar 08, 2022)1644833
1-45329315-T-A Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 Likely benign (Nov 25, 2022)819730
1-45329315-TG-T Familial adenomatous polyposis 2 • Hereditary cancer-predisposing syndrome Conflicting classifications of pathogenicity (Oct 15, 2023)127843
1-45329316-G-A Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 Uncertain significance (May 14, 2024)481812
1-45329316-G-T Familial adenomatous polyposis 2 • Hereditary cancer-predisposing syndrome Uncertain significance (Dec 18, 2023)1036120
1-45329317-C-T Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 Uncertain significance (Nov 04, 2022)926454
1-45329318-A-C Familial adenomatous polyposis 2 • Hereditary cancer-predisposing syndrome Uncertain significance (Dec 09, 2023)533307
1-45329318-A-G Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 Likely benign (Nov 23, 2020)926388

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MUTYHprotein_codingprotein_codingENST00000372098 1611308
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.26e-180.019412527284681257480.00189
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.2073223121.030.00002053474
Missense in Polyphen9692.4221.03871023
Synonymous-0.1271261241.010.000007241149
Loss of Function0.6623034.20.8780.00000180352

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001810.00181
Ashkenazi Jewish0.00009930.0000992
East Asian0.01630.0161
Finnish0.000.00
European (Non-Finnish)0.0004870.000484
Middle Eastern0.01630.0161
South Asian0.002320.00216
Other0.0006640.000652

dbNSFP

Source: dbNSFP

Function
FUNCTION: Involved in oxidative DNA damage repair. Initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. Possesses both adenine and 2- OH-A DNA glycosylase activities. {ECO:0000269|PubMed:10684930, ECO:0000269|PubMed:20418187, ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570, ECO:0000269|PubMed:26694661}.;
Disease
DISEASE: Familial adenomatous polyposis 2 (FAP2) [MIM:608456]: A condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma. {ECO:0000269|PubMed:11818965, ECO:0000269|PubMed:12606733, ECO:0000269|PubMed:12853198, ECO:0000269|PubMed:15366000, ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072, ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:18091433, ECO:0000269|PubMed:18515411, ECO:0000269|PubMed:19953527, ECO:0000269|PubMed:20418187, ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570, ECO:0000269|PubMed:26694661}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. {ECO:0000269|PubMed:15273732, ECO:0000269|PubMed:25820570}. Note=The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations contribute to the development of a sub-set of sporadic gastric cancers in carriers of Helicobacter pylori (PubMed:15273732). {ECO:0000269|PubMed:15273732}.;
Pathway
Base excision repair - Homo sapiens (human);DNA Repair;Recognition and association of DNA glycosylase with site containing an affected purine;Cleavage of the damaged purine;Depurination;Base-Excision Repair, AP Site Formation;Resolution of Abasic Sites (AP sites);Base Excision Repair;Displacement of DNA glycosylase by APEX1 (Consensus)

Recessive Scores

pRec
0.291

Intolerance Scores

loftool
0.0243
rvis_EVS
0.11
rvis_percentile_EVS
62.1

Haploinsufficiency Scores

pHI
0.135
hipred
Y
hipred_score
0.562
ghis
0.517

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.684

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Mutyh
Phenotype
cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm;

Gene ontology

Biological process
DNA repair;base-excision repair;mismatch repair;depurination
Cellular component
nucleus;nucleoplasm;mitochondrion
Molecular function
purine-specific mismatch base pair DNA N-glycosylase activity;protein binding;DNA N-glycosylase activity;oxidized purine DNA binding;MutLalpha complex binding;MutLbeta complex binding;MutSalpha complex binding;MutSbeta complex binding;8-oxo-7,8-dihydroguanine DNA N-glycosylase activity;adenine/guanine mispair binding;metal ion binding;4 iron, 4 sulfur cluster binding