GeneBe

MLH3

mutL homolog 3, the group of MutL homologs

Basic information

Region (hg38): 14:75013769-75051532

Links

ENSG00000119684 ∙ NCBI:27030 ∙ OMIM:604395 ∙ HGNC:7128 ∙ Uniprot:Q9UHC1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • colorectal cancer, hereditary nonpolyposis, type 7 (Moderate), mode of inheritance: AD
  • colorectal cancer, hereditary nonpolyposis, type 7 (Limited), mode of inheritance: AR
  • colorectal cancer, hereditary nonpolyposis, type 7 (Moderate), mode of inheritance: AD
  • colorectal cancer, hereditary nonpolyposis, type 7 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Colorectal cancer, hereditary nonpolyposis type 7; Endometrial carcinomaADOncologicSurveillance to allow early detection and treatment of tumors (associated with colorectal cancer) may be beneficial to reduce morbidity and mortalityOncologic12702580; 16885347
The clinical significance of mutations in this gene is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MLH3 gene.

  • not_specified (2674 variants)
  • Colorectal_cancer,_hereditary_nonpolyposis,_type_7 (1208 variants)
  • Endometrial_carcinoma (177 variants)
  • Colorectal_cancer (166 variants)
  • MLH3-related_disorder (97 variants)
  • not_provided (74 variants)
  • Ovarian_cancer (10 variants)
  • Colorectal_cancer,_non-polyposis (3 variants)
  • Lynch_syndrome_1 (3 variants)
  • Lynch_syndrome (2 variants)
  • Hereditary_cancer (2 variants)
  • Hereditary_cancer-predisposing_syndrome (1 variants)
  • Carcinoma_of_colon (1 variants)
  • Endometrial_cancer (1 variants)
  • Premature_ovarian_failure (1 variants)
  • Astrocytoma_IDH-mutant (1 variants)
  • Hereditary_nonpolyposis_colorectal_neoplasms (1 variants)
  • Malignant_tumor_of_breast (1 variants)
  • Breast_carcinoma (1 variants)
  • Familial_cancer_of_breast (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MLH3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001040108.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
725
clinvar
1
clinvar
 728
missense
5
clinvar
1821
clinvar
149
clinvar
4
clinvar
 1979
nonsense
1
clinvar
46
clinvar
 47
start loss
2
 2
frameshift
2
clinvar
10
clinvar
96
clinvar
 108
splice donor/acceptor (+/-2bp)
1
clinvar
13
clinvar
1
clinvar
 15
Total 2 17 1980 874 6

Highest pathogenic variant AF is 0.00008178216

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MLH3protein_codingprotein_codingENST00000355774 1237769
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
4.90e-81.0012530134441257480.00178
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7366877430.9240.00003889650
Missense in Polyphen171184.030.929192321
Synonymous1.482402710.8850.00001452705
Loss of Function4.002253.60.4110.00000263750

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.01970.0197
Ashkenazi Jewish0.00009920.0000992
East Asian0.0002720.000272
Finnish0.002580.00250
European (Non-Finnish)0.0002460.000246
Middle Eastern0.0002720.000272
South Asian0.0005550.000555
Other0.0006510.000652

dbNSFP

Source: dbNSFP

Function
FUNCTION: Probably involved in the repair of mismatches in DNA.;
Disease
DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:11317354}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Mismatch repair - Homo sapiens (human) (Consensus)

Recessive Scores

pRec
0.153

Intolerance Scores

loftool
0.147
rvis_EVS
1.86
rvis_percentile_EVS
97.16

Haploinsufficiency Scores

pHI
0.186
hipred
Y
hipred_score
0.519
ghis
0.472

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.572

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Mlh3
Phenotype
endocrine/exocrine gland phenotype; reproductive system phenotype;

Gene ontology

Biological process
mismatch repair;synaptonemal complex assembly;reciprocal meiotic recombination;male meiotic nuclear division;female meiosis I;protein localization
Cellular component
synaptonemal complex;male germ cell nucleus;nucleus;chiasma;mismatch repair complex;MutLalpha complex
Molecular function
chromatin binding;satellite DNA binding;protein binding;ATP binding;ATPase activity;centromeric DNA binding;mismatched DNA binding