Seroatlas · Human Serome Atlas

MLH1

DNA mismatch repair protein Mlh1

Also known as: COCA2, FCC2, HNPCC, HNPCC2, MLH-1, MLH1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P40692
Gene
MLH1
Ensembl
ENSG00000076242
Chromosome
3
Canonical length
756 aa
Protein class
Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location
Nucleoplasm

OverviewNCBI Gene

The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

756 residues, UniProt reviewed canonical sequence.

>P40692|MLH1
     1  MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI VKEGGLKLIQ
    61  IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR GEALASISHV AHVTITTKTA
   121  DGKCAYRASY SDGKLKAPPK PCAGNQGTQI TVEDLFYNIA TRRKALKNPS EEYGKILEVV
   181  GRYSVHNAGI SFSVKKQGET VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF
   241  KMNGYISNAN YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP
   301  QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEMV
   361  KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL SKPLSSQPQA IVTEDKTDIS
   421  SGRARQQDEE MLELPAPAEV AAKNQSLEGD TTKGTSEMSE KRGPTSSNPR KRHREDSDVE
   481  MVEDDSRKEM TAACTPRRRI INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL
   541  AQHQTKLYLL NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE
   601  DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL EGLPIFILRL
   661  ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ QSEVPGSIPN SWKWTVEHIV
   721  YKALRSHILP PKHFTEDGNI LQLANLPDLY KVFERC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MLH1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.36
Highest tissue expression
46 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 46 nTPM
  • tongue: 40 nTPM
  • heart muscle: 30 nTPM
  • thymus: 26 nTPM
  • testis: 24 nTPM
  • tonsil: 23 nTPM

Single-cell type

  • cardiomyocytes: 89 nCPM
  • myonuclei: 83 nCPM
  • late primary spermatocytes: 80 nCPM
  • erythrocyte progenitors: 74 nCPM
  • monocyte progenitors: 60 nCPM
  • megakaryocyte progenitors: 57 nCPM

Immune cell

  • non-classical monocyte: 30 nTPM
  • intermediate monocyte: 23 nTPM
  • eosinophil: 15 nTPM
  • T-reg: 15 nTPM
  • myeloid DC: 14 nTPM
  • basophil: 13 nTPM

Brain region

  • white matter: 9.4 nTPM
  • medulla oblongata: 9 nTPM
  • hypothalamus: 8.5 nTPM
  • basal ganglia: 7.7 nTPM
  • cerebral cortex: 7.1 nTPM
  • choroid plexus: 6.9 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MLH1.

Disease | AllUniProt

Conditions MLH1 is implicated in, by any mechanism.

Disease | GeneticClinVar

1,941 pathogenic / likely-pathogenic of 6,280 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

ReferencesPubMed · IEDB

Publications for MLH1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

1 publication

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.57
gnomAD pLI
0
gnomAD missense Z
-0.3
DepMap mean gene effect
-0.04
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MLH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MLH1 as an antibody target. Whether an autoantibody or antibody against MLH1 could matter depends on whether native MLH1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MLH1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label MLH1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/MLH1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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