Mlh1 mutL homolog 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mlh1provided by MGI
Official Full Name: mutL homolog 1provided by MGI
Primary source: MGI:MGI:101938
See related: Ensembl:ENSMUSG00000032498 AllianceGenome:MGI:101938
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: 1110035C23Rik
Summary: Enables chromatin binding activity and guanine/thymine mispair binding activity. Involved in positive regulation of isotype switching to IgA isotypes and positive regulation of isotype switching to IgG isotypes. Acts upstream of or within several processes, including DNA metabolic process; meiotic nuclear division; and regulation of nucleobase-containing compound metabolic process. Located in condensed nuclear chromosome and male germ cell nucleus. Part of MutLalpha complex. Is expressed in several structures, including central nervous system; endocrine gland; genitourinary system; oral epithelium; and respiratory system. Used to study Lynch syndrome. Human ortholog(s) of this gene implicated in Lynch syndrome (multiple); gastrointestinal system cancer (multiple); lung cancer; mismatch repair cancer syndrome; and sporadic breast cancer. Orthologous to human MLH1 (mutL homolog 1). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in CNS E11.5 (RPKM 5.9), limb E14.5 (RPKM 4.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 F3; 9 60.92 cM

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (111057296..111100854, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (111228228..111271786, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Resolution of sequence divergence for repeat-mediated deletions shows a polarity that is mediated by MLH1.
Title: Resolution of sequence divergence for repeat-mediated deletions shows a polarity that is mediated by MLH1.
Mlh1 heterozygosity and promoter methylation associates with microsatellite instability in mouse sperm.
Title: Mlh1 heterozygosity and promoter methylation associates with microsatellite instability in mouse sperm.
Tissue-specific reduction in MLH1 expression induces microsatellite instability in intestine of Mlh1(+/-) mice.
Title: Tissue-specific reduction in MLH1 expression induces microsatellite instability in intestine of Mlh1(+/-) mice.
Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.
Title: Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.
Promotion of somatic CAG repeat expansion by Fan1 knock-out in Huntington's disease knock-in mice is blocked by Mlh1 knock-out.
Title: Promotion of somatic CAG repeat expansion by Fan1 knock-out in Huntington's disease knock-in mice is blocked by Mlh1 knock-out.
Combined Gemcitabine and Immune-Checkpoint Inhibition Conquers Anti-PD-L1 Resistance in Low-Immunogenic Mismatch Repair-Deficient Tumors.
Title: Combined Gemcitabine and Immune-Checkpoint Inhibition Conquers Anti-PD-L1 Resistance in Low-Immunogenic Mismatch Repair-Deficient Tumors.
Three-step site-directed mutagenesis screen identifies pathogenic MLH1 variants associated with Lynch syndrome.
Title: Three-step site-directed mutagenesis screen identifies pathogenic MLH1 variants associated with Lynch syndrome.
Exposure to IR accelerated T-cell lymphoma induction in the Mlh1-/- mice.
Title: Mutational landscape of T-cell lymphoma in mice lacking the DNA mismatch repair gene Mlh1: no synergism with ionizing radiation.
Cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1.
Title: Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer.
a causal relationship between MLH1-deficiency and incidence of oncogenic point mutations in tyrosine kinases driving cell transformation and acquired resistance to kinase-targeted cancer therapies, is reported.
Title: Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.

Submit: New GeneRIF Correction See all GeneRIFs (41)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (3)
Endonuclease-mediated (12) 1 citation
Targeted (7) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC20223P1 (e-PCR)
- UniSTS:271886

PMC316497P1 (e-PCR)
- UniSTS:272995

Mlh1 (e-PCR), detects polymorphism
- UniSTS:496540

AI325952 (e-PCR)
- UniSTS:159925

AI561766 (e-PCR)
- UniSTS:185785

RH136168 (e-PCR)
- UniSTS:210163

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent DNA damage sensor activity	IEA Inferred from Electronic Annotation more info
enables MutSalpha complex binding	IEA Inferred from Electronic Annotation more info
contributes_to MutSalpha complex binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	IEA Inferred from Electronic Annotation more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables guanine/thymine mispair binding	IGI Inferred from Genetic Interaction more info	PubMed
enables guanine/thymine mispair binding	ISO Inferred from Sequence Orthology more info
enables single-stranded DNA binding	IEA Inferred from Electronic Annotation more info
contributes_to single-stranded DNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within DNA damage response	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within female meiosis chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within homologous chromosome pairing at meiosis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within homologous chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within isotype switching	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within leptotene	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within male meiosis chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within male meiotic nuclear division	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within meiotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within meiotic cell cycle	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within meiotic chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within meiotic metaphase I homologous chromosome alignment	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within meiotic spindle midzone assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within meiotic telomere clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mismatch repair	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within mismatch repair	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mismatch repair	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within negative regulation of mitotic recombination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within nuclear-transcribed mRNA poly(A) tail shortening	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within oogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of isotype switching to IgA isotypes	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of isotype switching to IgG isotypes	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within reciprocal meiotic recombination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within resolution of meiotic recombination intermediates	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to bacterium	IEP Inferred from Expression Pattern more info	PubMed
involved_in somatic hypermutation of immunoglobulin genes	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within somatic hypermutation of immunoglobulin genes	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within somatic recombination of immunoglobulin gene segments	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within somatic recombination of immunoglobulin genes involved in immune response	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within spermatogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of MutLalpha complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MutLalpha complex	IDA Inferred from Direct Assay more info	PubMed
located_in chiasma	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in condensed chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in condensed chromosome	IMP Inferred from Mutant Phenotype more info	PubMed
located_in condensed nuclear chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in late recombination nodule	IDA Inferred from Direct Assay more info	PubMed
located_in male germ cell nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in synaptonemal complex	IDA Inferred from Direct Assay more info	PubMed
located_in synaptonemal complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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Preferred Names: DNA mismatch repair protein Mlh1

Names: colon cancer, nonpolyposis type 2; mutL protein homolog 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001324522.1 → NP_001311451.1 DNA mismatch repair protein Mlh1 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses a frame-shifting alternate splice site in the 5' region and uses a downstream start codon, compared to variant 1. It encodes isoform 2 which lacks a large segment of the N-terminus, compared to isoform 1.

Source sequence(s)

AK163861, AK168849, BY327218

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:19 → 192

mutL; DNA mismatch repair endonuclease MutL

cd03483
Location:1 → 94

MutL_Trans_MLH1; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in ...

pfam16413
Location:265 → 519

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus
NM_026810.2 → NP_081086.2 DNA mismatch repair protein Mlh1 isoform 1

See identical proteins and their annotated locations for NP_081086.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AK145646, AK163861, BY327218

Consensus CDS

CCDS40784.1

UniProtKB/Swiss-Prot

Q3TG77, Q62454, Q9JK91

UniProtKB/TrEMBL

Q8VDI4

Related

ENSMUSP00000035079.4, ENSMUST00000035079.10

Conserved Domains (4) summary

cd03483
Location:211 → 335

MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...

TIGR00585
Location:6 → 315

mutl; DNA mismatch repair protein MutL

pfam16413
Location:505 → 760

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus

cl00075
Location:31 → 132

HATPase_c; Histidine kinase-like ATPases; This family includes several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

111057296..111100854 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036154640.1 → XP_036010533.1 DNA mismatch repair protein Mlh1 isoform X3

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:37 → 179

mutL; DNA mismatch repair endonuclease MutL

pfam16413
Location:252 → 506

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus

cl02783
Location:42 → 81

TopoII_MutL_Trans; MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second ...
XM_006511951.4 → XP_006512014.1 DNA mismatch repair protein Mlh1 isoform X4

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (1) summary

pfam16413
Location:165 → 419

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus
XM_006511948.4 → XP_006512011.1 DNA mismatch repair protein Mlh1 isoform X2

See identical proteins and their annotated locations for XP_006512011.1

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:19 → 192

mutL; DNA mismatch repair endonuclease MutL

cd03483
Location:1 → 94

MutL_Trans_MLH1; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in ...

pfam16413
Location:265 → 519

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus
XM_036154639.1 → XP_036010532.1 DNA mismatch repair protein Mlh1 isoform X3

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:37 → 179

mutL; DNA mismatch repair endonuclease MutL

pfam16413
Location:252 → 506

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus

cl02783
Location:42 → 81

TopoII_MutL_Trans; MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second ...
XM_036154636.1 → XP_036010529.1 DNA mismatch repair protein Mlh1 isoform X2

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:19 → 192

mutL; DNA mismatch repair endonuclease MutL

cd03483
Location:1 → 94

MutL_Trans_MLH1; transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in ...

pfam16413
Location:265 → 519

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus
XM_011242935.3 → XP_011241237.1 DNA mismatch repair protein Mlh1 isoform X1

UniProtKB/TrEMBL

Q8VDI4

Conserved Domains (2) summary

TIGR00585
Location:23 → 268

mutl; DNA mismatch repair protein MutL

pfam16413
Location:459 → 713

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus
XM_036154637.1 → XP_036010530.1 DNA mismatch repair protein Mlh1 isoform X3

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:37 → 179

mutL; DNA mismatch repair endonuclease MutL

pfam16413
Location:252 → 506

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus

cl02783
Location:42 → 81

TopoII_MutL_Trans; MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second ...
XM_030244079.1 → XP_030099939.1 DNA mismatch repair protein Mlh1 isoform X1

UniProtKB/TrEMBL

Q8VDI4

Conserved Domains (2) summary

TIGR00585
Location:23 → 268

mutl; DNA mismatch repair protein MutL

pfam16413
Location:459 → 713

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus
XM_036154638.1 → XP_036010531.1 DNA mismatch repair protein Mlh1 isoform X3

UniProtKB/TrEMBL

Q9CTA7

Conserved Domains (3) summary

PRK00095
Location:37 → 179

mutL; DNA mismatch repair endonuclease MutL

pfam16413
Location:252 → 506

Mlh1_C; DNA mismatch repair protein Mlh1 C-terminus

cl02783
Location:42 → 81

TopoII_MutL_Trans; MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second ...