Provide a comprehensive cross-database identifier and functional mapping reference for human MLH1. This should serve as a definitive lookup resource for researchers. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 1: GENE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Provide ALL gene-level database identifiers: - HGNC ID and approved symbol - Ensembl gene ID (ENSG) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 2: TRANSCRIPT IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL transcript-level identifiers: - Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.) How many total transcripts? - RefSeq transcripts: ALL NM_ mRNA accessions Mark which is MANE Select (canonical clinical standard) - CCDS IDs: ALL consensus coding sequence identifiers For the CANONICAL/MANE SELECT transcript: - List ALL exon IDs (ENSE) with genomic coordinates - Total exon count ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 3: PROTEIN IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL protein-level identifiers: - UniProt accessions: ALL entries (reviewed and unreviewed) Mark the canonical reviewed entry - RefSeq protein: ALL NP_ accessions Protein domains and families: - List ALL annotated domains/families with identifiers - Include: domain name, type (domain/family/superfamily), and ID ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 4: STRUCTURE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Experimental structures: - List ALL PDB structure IDs - For each: experimental method (X-ray, NMR, Cryo-EM) and resolution - Total PDB structure count Predicted structures: - AlphaFold model ID and confidence metrics (pLDDT) ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 5: CROSS-SPECIES ORTHOLOGS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List orthologous genes in key model organisms (where available): - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 6: CLINICAL VARIANTS & AI PREDICTIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Clinical variant annotations: - Total variant count in clinical databases - Breakdown by classification: Pathogenic, Likely Pathogenic, Uncertain Significance (VUS), Likely Benign, Benign - List TOP 50 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: Total count List TOP 50 predicted splice-altering variants with delta scores - Missense pathogenicity predictions: Total count List TOP 50 predicted pathogenic missense variants with scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Pathway membership: - List ALL biological pathways this gene participates in - Include pathway IDs and names - Total pathway count Gene Ontology annotations: - Biological Process: count and TOP 20 terms with IDs - Molecular Function: count and TOP 20 terms with IDs - Cellular Component: count and TOP 20 terms with IDs ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Protein-protein interactions: - Total interaction count - List TOP 50 highest-confidence interacting proteins with scores Protein similarity (evolutionary and structural): - Structural/embedding similarity: How many similar proteins? List TOP 20 with similarity scores - Sequence homology: How many homologous proteins? List TOP 20 with identity/similarity scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene encodes a transcription factor: Downstream targets (genes regulated BY this TF): - Total target gene count - List TOP 50 target genes with regulation type (activates/represses) DNA binding profiles: - List ALL known binding motif IDs - Motif family classification Upstream regulators (TFs that regulate THIS gene): - List known transcriptional regulators with evidence type ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 10: DRUG & PHARMACOLOGY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene/protein is a drug target: Targeting molecules: - How many drug/compound molecules target this protein? - List TOP 30 molecules by development phase - Include: molecule ID, name, mechanism, highest development phase Clinical trials: - How many clinical trials involve drugs targeting this gene? - List TOP 20 trials with: trial ID, phase, status, intervention Pharmacogenomics: - Known drug-gene interactions affecting drug response - Dosing guidelines if any exist ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 11: EXPRESSION PROFILES ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Tissue expression: - Which tissues express this gene most highly? - List TOP 30 tissues with expression scores/levels - Note any tissue-specific or tissue-enriched patterns Cell type expression: - Which cell types show highest expression? - List TOP 30 cell types with expression scores - Note any cell type-specific patterns Single-cell expression data (if available): - Which single-cell datasets/experiments include this gene? - Notable cell population patterns ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 12: DISEASE ASSOCIATIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Mendelian/monogenic disease links: - What diseases are caused by mutations in this gene? - List ALL associated diseases with: disease name, disease ID, inheritance pattern, evidence level Phenotype associations: - What clinical phenotypes are associated with this gene? - List TOP 50 phenotype terms with IDs Complex trait associations (GWAS): - What traits/diseases are linked via genome-wide association studies? - List TOP 30 GWAS associations with: trait, study ID, p-value, effect size if available ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ FORMATTING REQUIREMENTS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ - Present each section with clear headers - Use tables for listing multiple items - Always include COUNTS for every category - For lists with 50 items: show total count + TOP 50 - For lists with

Question

Provide a comprehensive cross-database identifier and functional mapping
reference for human MLH1. This should serve as a definitive
lookup resource for researchers.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 1: GENE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Provide ALL gene-level database identifiers:
- HGNC ID and approved symbol
- Ensembl gene ID (ENSG)
- NCBI Entrez Gene ID
- OMIM gene/locus ID
- Genomic location: chromosome, start position, end position, strand

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 2: TRANSCRIPT IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL transcript-level identifiers:
- Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.)
  How many total transcripts?
- RefSeq transcripts: ALL NM_ mRNA accessions
  Mark which is MANE Select (canonical clinical standard)
- CCDS IDs: ALL consensus coding sequence identifiers

For the CANONICAL/MANE SELECT transcript:
- List ALL exon IDs (ENSE) with genomic coordinates
- Total exon count

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 3: PROTEIN IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL protein-level identifiers:
- UniProt accessions: ALL entries (reviewed and unreviewed)
  Mark the canonical reviewed entry
- RefSeq protein: ALL NP_ accessions

Protein domains and families:
- List ALL annotated domains/families with identifiers
- Include: domain name, type (domain/family/superfamily), and ID

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 4: STRUCTURE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Experimental structures:
- List ALL PDB structure IDs
- For each: experimental method (X-ray, NMR, Cryo-EM) and resolution
- Total PDB structure count

Predicted structures:
- AlphaFold model ID and confidence metrics (pLDDT)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: CROSS-SPECIES ORTHOLOGS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List orthologous genes in key model organisms (where available):
- Mouse (Mus musculus): gene ID, symbol
- Rat (Rattus norvegicus): gene ID, symbol
- Zebrafish (Danio rerio): gene ID, symbol
- Fruit fly (Drosophila melanogaster): gene ID, symbol
- Worm (C. elegans): gene ID, symbol
- Yeast (S. cerevisiae): gene ID, symbol

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 6: CLINICAL VARIANTS & AI PREDICTIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Clinical variant annotations:
- Total variant count in clinical databases
- Breakdown by classification: Pathogenic, Likely Pathogenic,
  Uncertain Significance (VUS), Likely Benign, Benign
- List TOP 50 pathogenic/likely pathogenic variants with:
  variant ID, HGVS notation, associated condition

AI-based variant effect predictions:
- Splice effect predictions: Total count
  List TOP 50 predicted splice-altering variants with delta scores
- Missense pathogenicity predictions: Total count
  List TOP 50 predicted pathogenic missense variants with scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Pathway membership:
- List ALL biological pathways this gene participates in
- Include pathway IDs and names
- Total pathway count

Gene Ontology annotations:
- Biological Process: count and TOP 20 terms with IDs
- Molecular Function: count and TOP 20 terms with IDs
- Cellular Component: count and TOP 20 terms with IDs

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Protein-protein interactions:
- Total interaction count
- List TOP 50 highest-confidence interacting proteins with scores

Protein similarity (evolutionary and structural):
- Structural/embedding similarity: How many similar proteins?
  List TOP 20 with similarity scores
- Sequence homology: How many homologous proteins?
  List TOP 20 with identity/similarity scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene encodes a transcription factor:

Downstream targets (genes regulated BY this TF):
- Total target gene count
- List TOP 50 target genes with regulation type (activates/represses)

DNA binding profiles:
- List ALL known binding motif IDs
- Motif family classification

Upstream regulators (TFs that regulate THIS gene):
- List known transcriptional regulators with evidence type

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 10: DRUG & PHARMACOLOGY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene/protein is a drug target:

Targeting molecules:
- How many drug/compound molecules target this protein?
- List TOP 30 molecules by development phase
- Include: molecule ID, name, mechanism, highest development phase

Clinical trials:
- How many clinical trials involve drugs targeting this gene?
- List TOP 20 trials with: trial ID, phase, status, intervention

Pharmacogenomics:
- Known drug-gene interactions affecting drug response
- Dosing guidelines if any exist

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 11: EXPRESSION PROFILES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Tissue expression:
- Which tissues express this gene most highly?
- List TOP 30 tissues with expression scores/levels
- Note any tissue-specific or tissue-enriched patterns

Cell type expression:
- Which cell types show highest expression?
- List TOP 30 cell types with expression scores
- Note any cell type-specific patterns

Single-cell expression data (if available):
- Which single-cell datasets/experiments include this gene?
- Notable cell population patterns

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 12: DISEASE ASSOCIATIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Mendelian/monogenic disease links:
- What diseases are caused by mutations in this gene?
- List ALL associated diseases with: disease name, disease ID,
  inheritance pattern, evidence level

Phenotype associations:
- What clinical phenotypes are associated with this gene?
- List TOP 50 phenotype terms with IDs

Complex trait associations (GWAS):
- What traits/diseases are linked via genome-wide association studies?
- List TOP 30 GWAS associations with: trait, study ID, p-value,
  effect size if available

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
FORMATTING REQUIREMENTS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
- Present each section with clear headers
- Use tables for listing multiple items
- Always include COUNTS for every category
- For lists with >50 items: show total count + TOP 50
- For lists with <50 items: show ALL items
- Always include database identifiers (IDs), not just names
- Mark canonical/primary/reviewed entries where applicable
- If a section has no data available, state "No data available"
  rather than omitting the section

Accepted Answer

Section 1: Gene Identifiers
DatabaseIdentifierDescription HGNC IDHGNC:7127Approved symbol HGNC SymbolMLH1mutL homolog 1 Ensembl GeneENSG00000076242Ensembl gene ID NCBI Entrez Gene4292NCBI Gene ID OMIM Gene120436Gene/Locus entry StatusApprovedprotein-coding gene Aliases: HNPCC, FCC2, HNPCC2, MLH-1, COCA2 Gene Groups: MutL homologs, BRCA1-associated genome surveillance complex Genomic Location (GRCh38) AttributeValue Chromosome3 Cytogenetic Band3p22.2 Start Position36,993,226 End …

Transcript ID	Biotype	Start	End	Status
ENST00000231790	protein_coding	36,993,518	37,050,846	Canonical
ENST00000413740	protein_coding	36,993,357	37,050,846
ENST00000429117	protein_coding	36,993,826	37,050,846
ENST00000435176	protein_coding	36,993,804	37,050,844
ENST00000441265	protein_coding	36,993,826	37,047,737
ENST00000450420	protein_coding	36,993,518	37,050,537
ENST00000455445	protein_coding	36,993,798	37,050,706
ENST00000456676	protein_coding	36,993,518	37,050,844
ENST00000458205	protein_coding	36,993,776	37,050,846
ENST00000466900	protein_coding	36,993,848	37,050,844
ENST00000485889	protein_coding	36,993,827	37,050,846
ENST00000492474	protein_coding	36,993,791	37,050,896
ENST00000536378	protein_coding	36,993,350	37,050,842
ENST00000539477	protein_coding	36,993,804	37,050,783
ENST00000616768	protein_coding	36,993,472	37,050,846
ENST00000673673	protein_coding	36,993,226	37,050,799
ENST00000673715	protein_coding	36,993,523	37,047,740
ENST00000673899	protein_coding	36,993,489	37,050,767
ENST00000673990	protein_coding	36,993,785	37,050,807
ENST00000674019	protein_coding	36,993,764	37,050,823
ENST00000713802	protein_coding	36,993,542	37,050,841
ENST00000931189	protein_coding	36,993,487	37,050,843
ENST00000931190	protein_coding	36,993,491	37,050,846
ENST00000931191	protein_coding	36,993,545	37,050,841
ENST00000948704	protein_coding	36,993,487	37,050,844
ENST00000948705	protein_coding	36,993,540	37,050,842
ENST00000413212	nonsense_mediated_decay	36,993,785	37,050,823
ENST00000432299	nonsense_mediated_decay	36,993,524	37,050,823
ENST00000447829	nonsense_mediated_decay	36,993,785	37,050,807
ENST00000454028	nonsense_mediated_decay	36,993,534	37,050,846
ENST00000457004	nonsense_mediated_decay	36,993,516	37,014,494
ENST00000458009	nonsense_mediated_decay	36,993,518	37,050,846
ENST00000673897	nonsense_mediated_decay	36,993,531	37,050,794
ENST00000673947	nonsense_mediated_decay	36,993,539	37,050,814
ENST00000673972	nonsense_mediated_decay	36,993,515	37,050,827
ENST00000674111	nonsense_mediated_decay	36,993,495	37,050,796
ENST00000442249	retained_intron	36,993,533	37,026,093
ENST00000476172	retained_intron	36,993,785	36,998,096
ENST00000673686	retained_intron	36,993,785	36,998,085
ENST00000673713	retained_intron	36,993,517	37,026,060
ENST00000673741	retained_intron	37,046,754	37,050,843
ENST00000673889	retained_intron	37,017,334	37,050,799
ENST00000674107	retained_intron	36,993,833	37,030,353
ENST00000674125	retained_intron	37,028,664	37,050,838

Accession	Type	Status	MANE Select
NM_000249	mRNA	REVIEWED	✓ Yes
NM_001167617	mRNA	REVIEWED	No
NM_001167618	mRNA	REVIEWED	No
NM_001167619	mRNA	REVIEWED	No
NM_001258271	mRNA	REVIEWED	No
NM_001258273	mRNA	REVIEWED	No
NM_001258274	mRNA	REVIEWED	No
NM_001354615	mRNA	REVIEWED	No
NM_001354616	mRNA	REVIEWED	No
NM_001354617	mRNA	REVIEWED	No
NM_001354618	mRNA	REVIEWED	No
NM_001354619	mRNA	REVIEWED	No
NM_001354620	mRNA	REVIEWED	No
NM_001354621	mRNA	REVIEWED	No
NM_001354622	mRNA	REVIEWED	No
NM_001354623	mRNA	REVIEWED	No
NM_001354624	mRNA	REVIEWED	No
NM_001354625	mRNA	REVIEWED	No
NM_001354626	mRNA	REVIEWED	No
NM_001354627	mRNA	REVIEWED	No
NM_001354628	mRNA	REVIEWED	No
NM_001354629	mRNA	REVIEWED	No
NM_001354630	mRNA	REVIEWED	No

CCDS ID	Status
CCDS2663	Primary
CCDS54562	Alternative
CCDS54563	Alternative

Exon ID	Start	End	Length (bp)
ENSE00004012715	36,993,518	36,993,663	146
ENSE00003496022	36,996,619	36,996,709	91
ENSE00003599036	37,000,955	37,001,053	99
ENSE00003635406	37,004,401	37,004,474	74
ENSE00003533853	37,006,991	37,007,063	73
ENSE00003633623	37,008,814	37,008,905	92
ENSE00003521968	37,011,820	37,011,862	43
ENSE00003516787	37,012,011	37,012,099	89
ENSE00003656033	37,014,432	37,014,544	113
ENSE00001716871	37,017,506	37,017,599	94
ENSE00003785627	37,020,310	37,020,463	154
ENSE00003688106	37,025,637	37,026,007	371
ENSE00003680564	37,028,784	37,028,932	149
ENSE00001730188	37,040,186	37,040,294	109
ENSE00001747618	37,042,268	37,042,331	64
ENSE00001748897	37,047,519	37,047,683	165
ENSE00001593400	37,048,517	37,048,609	93
ENSE00001785296	37,048,904	37,049,017	114
ENSE00003902581	37,050,486	37,050,846	361

Accession	Name	Status	Canonical
P40692	DNA mismatch repair protein Mlh1	Reviewed (Swiss-Prot)	✓ Yes
A0A087WX20	MLH1 isoform	Unreviewed	No
A0A669KAW3	MLH1 isoform	Unreviewed	No
A0A669KB03	MLH1 isoform	Unreviewed	No
A0A669KBB4	MLH1 isoform	Unreviewed	No
A0A669KBK2	MLH1 isoform	Unreviewed	No
A0AAQ5BGN3	MLH1 isoform	Unreviewed	No
A0AAQ5BGZ2	MLH1 isoform	Unreviewed	No
C9JZ54	MLH1 isoform	Unreviewed	No
E7EUC9	MLH1 isoform	Unreviewed	No
E9PF25	MLH1 isoform	Unreviewed	No
F2Z298	MLH1 isoform	Unreviewed	No
H0Y4N0	MLH1 isoform	Unreviewed	No
H0Y5L7	MLH1 isoform	Unreviewed	No
H0Y5U4	MLH1 isoform	Unreviewed	No
H0Y793	MLH1 isoform	Unreviewed	No
H0Y806	MLH1 isoform	Unreviewed	No
H0Y818	MLH1 isoform	Unreviewed	No

MLH1 Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Description
HGNC ID	HGNC:7127	Approved symbol
HGNC Symbol	MLH1	mutL homolog 1
Ensembl Gene	ENSG00000076242	Ensembl gene ID
NCBI Entrez Gene	4292	NCBI Gene ID
OMIM Gene	120436	Gene/Locus entry
Status	Approved	protein-coding gene

Attribute	Value
Chromosome	3
Cytogenetic Band	3p22.2
Start Position	36,993,226
End Position	37,050,896
Strand	+ (forward)
Gene Span	57,671 bp

Property	Value
Length	756 amino acids
Mass	84,601 Da
Alternative Names	MutL protein homolog 1

Accession	Status	MANE Select
NP_000240	REVIEWED	✓ Yes
NP_001161089	REVIEWED	No
NP_001161090	REVIEWED	No
NP_001161091	REVIEWED	No
NP_001245200	REVIEWED	No
NP_001245202	REVIEWED	No
NP_001245203	REVIEWED	No
NP_001341544	REVIEWED	No
NP_001341545	REVIEWED	No
NP_001341546	REVIEWED	No
NP_001341547	REVIEWED	No
NP_001341548	REVIEWED	No
NP_001341549	REVIEWED	No
NP_001341550	REVIEWED	No
NP_001341551	REVIEWED	No
NP_001341552	REVIEWED	No
NP_001341553	REVIEWED	No
NP_001341554	REVIEWED	No
NP_001341555	REVIEWED	No
NP_001341556	REVIEWED	No
NP_001341557	REVIEWED	No
NP_001341558	REVIEWED	No
NP_001341559	REVIEWED	No

InterPro ID	Name	Type
IPR002099	MutL/Mlh/PMS	Family
IPR038973	MutL/Mlh/Pms-like	Family
IPR013507	DNA_mismatch_S5_2-like	Domain
IPR032189	Mlh1_C	Domain
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR014762	DNA_mismatch_repair_CS	Conserved_site

PDB ID	Title	Method	Resolution (Å)	Organism
3RBN	Crystal structure of MutL protein homolog 1 isoform 1	X-RAY DIFFRACTION	2.16	Homo sapiens
4P7A	Crystal Structure of human MLH1	X-RAY DIFFRACTION	2.30	Homo sapiens
5U5P	Importin-alpha with MLH1 NLS Peptide	X-RAY DIFFRACTION	2.171	Mus musculus/Synthetic
6WBA	Importin alpha MLH1-R470A NLS Peptide Complex	X-RAY DIFFRACTION	2.151	Mus musculus/Synthetic
6WBB	Importin alpha MLH1-E475A NLS peptide complex	X-RAY DIFFRACTION	2.663	Mus musculus/Synthetic
6WBC	Importin alpha MLH1-R472K NLS Peptide Complex	X-RAY DIFFRACTION	2.15	Mus musculus/Synthetic
7M60	Importin alpha MLH1-S467A NLS Peptide Complex	X-RAY DIFFRACTION	2.30	Mus musculus/Synthetic

Organism	Gene ID	Symbol	UniProt
Mouse (Mus musculus)	ENSMUSG00000032498	Mlh1	P97679
Rat (Rattus norvegicus)	ENSRNOG00000033809	Mlh1	Q9JK91
Zebrafish (Danio rerio)	ENSDARG00000025948	mlh1	-
Fruit fly (Drosophila melanogaster)	FBGN0011659	Mlh1	Q9ZRV4
Worm (C. elegans)	WBGENE00003373	mlh-1	Q54KD8
Yeast (S. cerevisiae)	YMR167W	MLH1	P38920

Classification	Count
Pathogenic	>500
Likely pathogenic	>300
Uncertain significance (VUS)	>4,000
Likely benign	Multiple
Benign	Multiple

ClinVar ID	HGVS Notation	Type	Review Status
142856	c.117-2A>G	SNV	Reviewed by expert panel
1012206	c.1003del (p.Leu335fs)	Deletion	Multiple submitters
1048862	c.497T>G (p.Leu166Ter)	SNV	Multiple submitters
1049670	c.1896+1G>C	SNV	Multiple submitters
1068948	c.406A>T (p.Lys136Ter)	SNV	Multiple submitters
1069408	c.1507del (p.Leu503fs)	Deletion	Multiple submitters
1070239	c.22del (p.Ile8fs)	Deletion	Multiple submitters
1070756	c.1408A>T (p.Arg470Ter)	SNV	Multiple submitters
1073257	c.1707del (p.Asn570fs)	Deletion	Multiple submitters
1074205	c.35del (p.Asp12fs)	Deletion	Multiple submitters
1074878	c.1830C>G (p.Tyr610Ter)	SNV	Multiple submitters
1076321	c.1888del (p.Ile630fs)	Deletion	Multiple submitters
1076485	c.1435_1453del (p.Val479fs)	Deletion	Multiple submitters
1076792	c.1983dup (p.Thr662fs)	Duplication	Multiple submitters
1177381	c.1695_1698del (p.Ile565fs)	Deletion	Multiple submitters
1195084	c.1713del (p.Phe571fs)	Deletion	Multiple submitters
1358070	c.1727T>G (p.Leu576Ter)	SNV	Multiple submitters
135851	c.2190del (p.Pro731fs)	Deletion	Multiple submitters
1365840	c.52_59del (p.Arg18fs)	Deletion	Multiple submitters
1368790	c.592G>T (p.Gly198Ter)	SNV	Multiple submitters
1372749	c.2043dup (p.Met682fs)	Duplication	Multiple submitters
1387037	c.813del (p.Ser271_Leu272insTer)	Deletion	Multiple submitters
1392794	c.1499del (p.Ile500fs)	Deletion	Multiple submitters
1402505	c.1809del (p.Glu605fs)	Deletion	Multiple submitters
1405246	c.1239dup (p.Glu414fs)	Duplication	Multiple submitters
141043	c.790+1G>T	SNV	Multiple submitters
1412554	c.1730C>A (p.Ser577Ter)	SNV	Multiple submitters
1443114	c.2195_2196del (p.Lys732fs)	Deletion	Multiple submitters
1451346	c.383del (p.Ala128fs)	Deletion	Multiple submitters
1452609	c.227dup (p.Cys77fs)	Duplication	Multiple submitters
1453286	c.2138_2151del (p.Lys713fs)	Deletion	Multiple submitters
1453590	c.2163del (p.Val720_Tyr721insTer)	Deletion	Multiple submitters
1068563	c.1921dup (p.Leu641fs)	Duplication	Multiple submitters
1023950	c.1681_1686del (p.Tyr561_Gln562del)	Deletion	Single submitter
1049302	c.1275dup (p.Gln426fs)	Duplication	Single submitter
1049396	c.1999del (p.Asp667fs)	Deletion	Single submitter
1049673	c.1367del (p.Thr455_Ser456insTer)	Deletion	Single submitter
1068760	c.2089dup (p.Leu697fs)	Duplication	Single submitter
1069316	c.1482T>A (p.Cys494Ter)	SNV	Single submitter
1069751	c.2039_2040delinsAG (p.Cys680Ter)	Indel	Single submitter
1069993	c.2099del (p.Gln700fs)	Deletion	Single submitter
1071267	c.2123_2126del (p.Ile708fs)	Deletion	Single submitter
1071293	c.194_195insAT (p.Thr66fs)	Insertion	Single submitter
1071631	c.837_838del (p.Tyr280fs)	Microsatellite	Single submitter
1071933	c.929_930del (p.Thr310fs)	Microsatellite	Single submitter
1072166	c.2046_2052del (p.Met682fs)	Deletion	Single submitter
1074920	c.790del (p.His264fs)	Deletion	Single submitter
1075393	c.2028del (p.Ser677fs)	Deletion	Single submitter
1076815	c.979dup (p.Gln327fs)	Duplication	Single submitter
1255698	c.1A>T (p.Met1Leu)	SNV	Single submitter

Variant	Gene	Effect	Delta Score
3:36996617:A:AG	MLH1	acceptor_gain	1.00
3:36996618:G:GA	MLH1	acceptor_gain	1.00
3:36996618:GTTT:G	MLH1	acceptor_gain	1.00
3:36996618:GTTTA:G	MLH1	acceptor_gain	1.00
3:36996707:AGGG:A	MLH1	donor_loss	1.00
3:36996708:GG:G	MLH1	donor_gain	1.00
3:36996708:GGGTA:G	MLH1	donor_loss	1.00
3:36996709:GG:G	MLH1	donor_gain	1.00
3:36996710:G:A	MLH1	donor_loss	1.00
3:36996710:G:GG	MLH1	donor_gain	1.00
3:36996711:T:TC	MLH1	donor_loss	1.00
3:36993672:G:GT	MLH1	donor_gain	1.00
3:36993614:G:GT	MLH1	donor_gain	0.99
3:36993614:G:T	MLH1	donor_gain	0.99
3:36993633:C:G	MLH1	donor_gain	0.99
3:36993696:GGC:G	MLH1	donor_gain	0.99
3:36993836:GACC:G	MLH1	donor_gain	0.99
3:36994235:C:CA	MLH1	acceptor_gain	0.99
3:36994236:G:A	MLH1	acceptor_gain	0.99
3:36994347:G:GG	MLH1	donor_gain	0.99
3:36996608:T:TA	MLH1	acceptor_gain	0.99
3:36996613:T:TA	MLH1	acceptor_gain	0.99
3:36996613:TGCCA:T	MLH1	acceptor_loss	0.99
3:36996614:GCCAG:G	MLH1	acceptor_loss	0.99
3:36996615:CCAGT:C	MLH1	acceptor_loss	0.99
3:36996616:CA:C	MLH1	acceptor_loss	0.99
3:36996617:A:AT	MLH1	acceptor_loss	0.99
3:36996618:G:T	MLH1	acceptor_loss	0.99
3:36996618:GT:G	MLH1	acceptor_gain	0.99
3:36996618:GTT:G	MLH1	acceptor_gain	0.99
3:36996705:TCAGG:T	MLH1	donor_gain	0.99
3:36996706:CAGG:C	MLH1	donor_gain	0.99
3:36996707:AGG:A	MLH1	donor_gain	0.99
3:36996708:GGG:G	MLH1	donor_gain	0.99
3:36994231:ATTTC:A	MLH1	acceptor_gain	0.97
3:36993887:GAGT:G	MLH1	donor_gain	0.97
3:36995502:G:GT	MLH1	donor_gain	0.97
3:36993809:GCC:G	MLH1	donor_gain	0.96
3:36993886:GGAGT:G	MLH1	donor_gain	0.95
3:36993887:GAGTG:G	MLH1	donor_gain	0.95
3:36993889:GT:G	MLH1	donor_gain	0.95
3:36993901:GAATA:G	MLH1	donor_gain	0.95
3:36994318:G:T	MLH1	donor_gain	0.95
3:36993812:A:AG	MLH1	donor_gain	0.94
3:36993891:G:GG	MLH1	donor_gain	0.94
3:36993761:T:G	MLH1	donor_gain	0.94
3:36994400:T:G	MLH1	donor_gain	0.94
3:36996619:TTTAG:T	MLH1	acceptor_loss	0.94
3:36996620:TTAGA:T	MLH1	acceptor_loss	0.94
3:36996621:TAGAT:T	MLH1	acceptor_loss	0.94

Pfam ID	Name
PF01119	DNA_mis_repair
PF13589	HATPase_c_3
PF16413	MutL_C

Variant	Protein Change	Pathogenicity Score	Classification
3:36993600:G:C	R18P	1.000	likely_pathogenic
3:36993579:T:C	L11P	0.999	likely_pathogenic
3:36993603:T:G	I19S	0.999	likely_pathogenic
3:36993606:C:A	A20E	0.998	likely_pathogenic
3:36993605:G:C	A20P	0.998	likely_pathogenic
3:36993608:G:C	A21P	0.998	likely_pathogenic
3:36993609:C:A	A21E	0.999	likely_pathogenic
3:36993611:G:A	G22R	0.998	likely_pathogenic
3:36993611:G:C	G22R	0.998	likely_pathogenic
3:36993611:G:T	G22W	0.998	likely_pathogenic
3:36993612:G:A	G22E	0.999	likely_pathogenic
3:36993570:T:A	I8N	0.998	likely_pathogenic
3:36993570:T:C	I8T	0.996	likely_pathogenic
3:36993570:T:G	I8S	0.995	likely_pathogenic
3:36993599:C:A	R18S	0.995	likely_pathogenic
3:36993614:G:A	E23K	0.996	likely_pathogenic
3:36993616:A:C	E23D	0.996	likely_pathogenic
3:36993615:A:T	E23V	0.995	likely_pathogenic
3:36993618:T:A	V24D	0.999	likely_pathogenic
3:36993618:T:C	V24A	0.995	likely_pathogenic
3:36993621:T:A	I25N	0.999	likely_pathogenic
3:36993621:T:G	I25S	0.996	likely_pathogenic
3:36993594:T:A	V16E	0.992	likely_pathogenic
3:36993591:T:A	V15E	0.993	likely_pathogenic
3:36993593:G:C	V16L	0.980	likely_pathogenic
3:36993609:C:T	A21V	0.993	likely_pathogenic
3:36993612:G:T	G22V	0.994	likely_pathogenic
3:36993569:A:T	I8F	0.970	likely_pathogenic
3:36993593:G:A	V16M	0.970	likely_pathogenic
3:36993578:C:G	L11V	0.968	likely_pathogenic
3:36993591:T:G	V15G	0.966	likely_pathogenic
3:36993609:C:G	A21G	0.971	likely_pathogenic
3:36993602:A:C	I19L	0.948	likely_pathogenic
3:36993602:A:T	I19F	0.994	likely_pathogenic
3:36993603:T:A	I19N	1.000	likely_pathogenic
3:36993603:T:C	I19T	0.998	likely_pathogenic
3:36993605:G:A	A20T	0.981	likely_pathogenic
3:36993606:C:G	A20G	0.963	likely_pathogenic
3:36993606:C:T	A20V	0.988	likely_pathogenic
3:36993608:G:A	A21T	0.992	likely_pathogenic

Pathway ID	Name	Disease Pathway
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	No
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	No
R-HSA-912446	Meiotic recombination	No
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes	No
R-HSA-5545483	Defective Mismatch Repair Associated With MLH1	Yes
R-HSA-5632987	Defective Mismatch Repair Associated With PMS2	Yes

GO ID	Term
GO:0006298	mismatch repair
GO:0000712	resolution of meiotic recombination intermediates
GO:0006303	double-strand break repair via nonhomologous end joining
GO:0007060	male meiosis chromosome segregation
GO:0007129	homologous chromosome pairing at meiosis
GO:0007283	spermatogenesis
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009617	response to bacterium
GO:0016321	female meiosis chromosome segregation
GO:0016446	somatic hypermutation of immunoglobulin genes
GO:0043060	meiotic metaphase I homologous chromosome alignment
GO:0045141	meiotic telomere clustering
GO:0045190	isotype switching
GO:0045950	negative regulation of mitotic recombination
GO:0048298	positive regulation of isotype switching to IgA isotypes
GO:0048304	positive regulation of isotype switching to IgG isotypes
GO:0048477	oogenesis
GO:0051257	meiotic spindle midzone assembly
GO:0000289	nuclear-transcribed mRNA poly(A) tail shortening

GO ID	Term
GO:0003682	chromatin binding
GO:0005524	ATP binding
GO:0008047	enzyme activator activity
GO:0016887	ATP hydrolysis activity
GO:0019899	enzyme binding
GO:0032137	guanine/thymine mispair binding
GO:0140664	ATP-dependent DNA damage sensor activity

GO ID	Term
GO:0000795	synaptonemal complex
GO:0001673	male germ cell nucleus
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005694	chromosome
GO:0005712	chiasma
GO:0005715	late recombination nodule
GO:0016020	membrane
GO:0032389	MutLalpha complex

Partner UniProt	Partner Gene	Confidence Score
P20585	MSH3	999
P43246	MSH2	999
P52701	MSH6	999
Q9UQ84	PMS2	998
P49751	EXO1	993
P54277	PMS1	993
P54278	MLH3	993
Q13315	ATM	992
Q9BX63	FANCJ/BRIP1	951
P38398	BRCA1	930
O95243	MBD4	921
Q9UIF7	RADX	914
P51587	BRCA2	905
P15056	BRAF	876
Q9BXW9	FANCD2	874
P01116	KRAS	868
P04637	TP53	868
O15457	RBBP8/CtIP	856
P42771	CDKN2A	856
P16455	MGMT	853
Q07864	POLE	852
Q9Y2M0	FAN1	844
O75771	RAD51B	838
P16422	EPCAM	837
P35249	RFC4	826
P32846	GPC1	825
O43196	ESCO1	824
O96017	CHK2	824
P60484	PTEN	811
P54132	BLM	808
P28340	DPYD	790
P42336	PIK3CA	788
O43502	RAD51C	787
O60934	NBN	775
Q14191	WRN	773
A2PYH4	MRE11	772
Q9Y5K1	PCNA	771
Q86YC2	FAM175A	766
P21359	NF1	764
Q06609	RAD51	758
P36894	BMPR1A	735
Q00765	RECC1	728
Q15831	STK11	726
P07992	ERCC1	725
Q9NS23	RINT1	719
Q9NXL9	RFWD3	716
P49959	MRE11A	715
P37173	TGFBR2	702
Q99728	BARD1	700

Partner	Interaction Type	Confidence
PMS2	direct interaction	0.97
BRIP1	physical association	0.94
MYOG	physical association	0.89
RADX	physical association	0.87
ZC3H11A	physical association	0.87
UBOX5	physical association	0.85
KPNA2	physical association	0.83
PMS1	physical association	0.83
CBY2	physical association	0.80
MLH3	physical association	0.78
MAGEA8	physical association	0.78
MSH3	physical association	0.74
PSMA1	physical association	0.74
TMSB4X	physical association	0.73
TASOR2	physical association	0.72
FRMD6	physical association	0.67
CCDC33	physical association	0.67

UniProt	Top Similarity	Avg Similarity
P43246 (MSH2)	0.9999	0.9384
Q5XXB5	0.9999	0.9384
Q9Z2D1	0.9995	0.9515
Q13614	0.9995	0.9504
Q02440	0.9990	0.9382
Q2PFX0	0.9989	0.9437
B2KI88	0.9988	0.9520
P43247 (PMS1)	0.9987	0.9419
Q3MHE4	0.9987	0.9413
P24860	0.9986	0.9370
O95292	0.9986	0.9447
Q08301	0.9985	0.9327
P14635	0.9985	0.9305
P30277	0.9984	0.9367
Q1LZG6	0.9984	0.9371
A6QNT8	0.9978	0.9246
O95486	0.9978	0.9213
Q9S9N4	0.9977	0.9340
O43502 (RAD51C)	0.9976	0.9410
Q3U2P1	0.9966	0.9268

UniProt	Species/Description	Top Identity (%)	BitScore
P97679	Mouse Mlh1	91.3	1349
Q9JK91	Rat Mlh1	91.3	1351
B5RL36	-	99.3	1193
B5RR29	-	99.3	1191
P54278	Human MLH3	97.4	1274
O51229	-	92.3	1112
Q0SNV1	-	92.5	1112
Q662F3	-	92.5	1115
A1QZ05	-	85.6	1051
P54280	Human MSH6	50.3	421
Q54KD8	C. elegans mlh-1	40.2	569
P38920	Yeast MLH1	39.7	467
Q9ZRV4	Fly Mlh1	39.2	510
Q9P7W6	-	37.3	438

Transcription Factor	Regulation Type	Confidence
TP53	Activation	-
BHLHE40	Unknown	High
BHLHE41	Repression	High
CEBPZ	Repression	High
GLI1	Unknown	High
GLI2	Unknown	High
HOXA5	Unknown	High
MLXIP	Unknown	High
BRIP1	Unknown	-
DNMT3A	Repression	-
E2F4	Unknown	-
HIF1A	Unknown	-
MAFG	Unknown	-
CTNNBL1	Unknown	Low
DNMT1	Unknown	Low
ESR2	Unknown	Low
HOXD1	Unknown	Low
TP73	Unknown	Low
WT1	Repression	Low

Attribute	Value
PharmGKB ID	PA240
VIP Gene	Yes (Very Important Pharmacogene)
Has CPIC Guideline	No
Has Variant Annotations	Yes

Attribute	Value
Expression Breadth	Ubiquitous
Total Present Calls	296
Total Absent Calls	4
Total Conditions	300
Max Expression Score	94.44
Average Expression Score	87.57
Gold Quality Count	294

Tissue (UBERON ID)	Expression	Score	Quality
Tibialis anterior (UBERON:0001385)	present	94.44	gold
Skeletal muscle of rectus abdominis (UBERON:0004511)	present	94.42	gold
Deltoid (UBERON:0001476)	present	94.37	gold
Left ventricle myocardium (UBERON:0006566)	present	94.30	gold
Heart left ventricle (UBERON:0002084)	present	93.97	gold
Cardiac ventricle (UBERON:0002082)	present	93.90	gold
Primordial germ cell in gonad	present	93.85	gold
Vastus lateralis (UBERON:0001379)	present	93.84	gold
Quadriceps femoris (UBERON:0001377)	present	93.78	gold
Apex of heart (UBERON:0002098)	present	93.60	gold
Skeletal muscle tissue (UBERON:0001134)	present	93.35	gold
Heart right ventricle (UBERON:0002080)	present	93.35	gold
Ganglionic eminence (UBERON:0004023)	present	93.22	gold
Muscle organ (UBERON:0001630)	present	92.99	gold
Skeletal muscle organ (UBERON:0014892)	present	92.99	gold
Biceps brachii (UBERON:0001507)	present	92.97	gold
Muscle tissue (UBERON:0002385)	present	92.79	gold
Heart (UBERON:0000948)	present	92.78	gold
Muscle of leg (UBERON:0001383)	present	92.75	gold
Ventricular zone (UBERON:0003053)	present	92.73	gold
Tibia (UBERON:0000979)	present	92.69	gold
Calcaneal tendon (UBERON:0003701)	present	92.62	gold
Gastrocnemius (UBERON:0001388)	present	92.53	gold
Diaphragm (UBERON:0001103)	present	92.49	gold
Pituitary gland (UBERON:0000007)	present	92.48	gold
Triceps brachii (UBERON:0001509)	present	92.45	gold
Adenohypophysis (UBERON:0002196)	present	92.41	gold
Skin of hip (UBERON:0001554)	present	92.34	gold
Right atrium auricular region (UBERON:0006631)	present	92.32	gold
Corpus callosum (UBERON:0002336)	present	92.23	gold

Disease	OMIM/MONDO	Inheritance	Evidence	Submitter
Lynch syndrome 2	OMIM:609310	AD	Definitive	Ambry, G2P
Lynch syndrome	MONDO:0005835	AD	Definitive	G2P
Mismatch repair cancer syndrome 1	OMIM:276300	AR	Definitive	Ambry, G2P
Muir-Torre syndrome	OMIM:158320	AD	Definitive	G2P
Lynch syndrome	ORPHANET:144	AD	Supportive	Orphanet
Muir-Torre syndrome	OMIM:158320	AD	Strong	Genomics England
Lynch syndrome 2	OMIM:609310	AD	Strong	Genomics England
Lynch syndrome 1	OMIM:120435	AD	Strong	Labcorp
Mismatch repair cancer syndrome 1	OMIM:276300	AR	Strong	Labcorp
Ovarian cancer	MONDO:0008170	AD	Strong	Genomics England
Muir-Torre syndrome	OMIM:158320	AD	Moderate	Ambry
Rhabdomyosarcoma	MONDO:0005212	AR	Moderate	Genomics England
Malignant pancreatic neoplasm	MONDO:0009831	AD	Moderate	Genomics England
Prostate cancer	MONDO:0008315	AD	Limited	Ambry
Breast cancer	MONDO:0007254	AD	Disputed	Ambry

Orphanet ID	Disease Name	Type	Gene Count	Phenotype Count
144	Lynch syndrome	Disease	9	62
252202	Constitutional mismatch repair deficiency syndrome	Disease	4	0

HPO ID	Phenotype
HP:0003003	Colon cancer
HP:0005227	Adenomatous colonic polyposis
HP:0100743	Neoplasm of the rectum
HP:0012114	Endometrial carcinoma
HP:0100615	Ovarian neoplasm
HP:0002894	Neoplasm of the pancreas
HP:0006753	Neoplasm of the stomach
HP:0006725	Pancreatic adenocarcinoma
HP:0040276	Adenocarcinoma of the colon
HP:0040274	Adenocarcinoma of the small intestine
HP:0006771	Duodenal adenocarcinoma
HP:0006758	Malignant genitourinary tract tumor
HP:0009726	Renal neoplasm
HP:0010786	Urinary tract neoplasm
HP:0002665	Lymphoma
HP:0012539	Non-Hodgkin lymphoma
HP:0012190	T-cell lymphoma
HP:0001909	Leukemia
HP:0004377	Hematological neoplasm
HP:0003002	Breast carcinoma
HP:0100031	Neoplasm of the thyroid gland
HP:0001402	Hepatocellular carcinoma
HP:0002896	Neoplasm of the liver
HP:0008069	Neoplasm of the skin
HP:0002671	Basal cell carcinoma
HP:0030410	Sebaceous gland carcinoma
HP:0009720	Adenoma sebaceum
HP:0009592	Astrocytoma
HP:0012174	Glioblastoma multiforme
HP:0033681	Oligodendroglioma
HP:0002888	Ependymoma
HP:0002885	Medulloblastoma
HP:0033682	Pleomorphic xanthoastrocytoma
HP:0100835	Benign neoplasm of the central nervous system
HP:0003006	Neuroblastoma
HP:0002893	Pituitary adenoma
HP:0002859	Rhabdomyosarcoma
HP:0010622	Neoplasm of the skeletal system
HP:0100684	Salivary gland neoplasm
HP:0012118	Laryngeal carcinoma
HP:0200008	Intestinal polyposis
HP:0006719	Benign gastrointestinal tract tumors
HP:0006778	Benign genitourinary tract neoplasm
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0003596	Middle age onset
HP:0001522	Death in infancy
HP:0100613	Death in early adulthood
HP:0007565	Multiple cafe-au-lait spots
HP:0009732	Plexiform neurofibroma

Study ID	Trait/Disease	Mapped Gene	P-value
GCST012206	Proximal colorectal cancer	MLH1	4×10⁻¹⁸
GCST90002401	Platelet distribution width	MLH1	2×10⁻¹⁸
GCST90013405	Liver enzyme levels (ALT)	MLH1	4×10⁻¹⁵
GCST004521	Autism spectrum disorder or schizophrenia	HSPD1P6-LINC02033	1×10⁻¹¹
GCST004946	Schizophrenia	TRANK1	3×10⁻¹¹
GCST90011898	Alanine aminotransferase levels	MLH1	2×10⁻⁸
GCST003158	Subjective response to lithium treatment	HSPD1P6-LINC02033	8×10⁻⁷

Database	Version/Access	URL
HGNC	Current	https://www.genenames.org
Ensembl	GRCh38	https://www.ensembl.org
NCBI Gene	Current	https://www.ncbi.nlm.nih.gov/gene
UniProt	Current	https://www.uniprot.org
OMIM	Current	https://omim.org
RefSeq	Current	https://www.ncbi.nlm.nih.gov/refseq
PDB	Current	https://www.rcsb.org
AlphaFold	v4	https://alphafold.ebi.ac.uk
InterPro	Current	https://www.ebi.ac.uk/interpro
ClinVar	Current	https://www.ncbi.nlm.nih.gov/clinvar
AlphaMissense	2023	https://alphamissense.hegelab.org
SpliceAI	Current	-
Reactome	Current	https://reactome.org
Gene Ontology	Current	http://geneontology.org
STRING	v12	https://string-db.org
IntAct	Current	https://www.ebi.ac.uk/intact
Bgee	Current	https://www.bgee.org
PharmGKB	Current	https://www.pharmgkb.org
GenCC	Current	https://thegencc.org
Orphanet	Current	https://www.orpha.net
HPO	Current	https://hpo.jax.org
GWAS Catalog	Current	https://www.ebi.ac.uk/gwas
CollecTRI	Current	https://collectri.github.io

Category	Key Data
Gene IDs	HGNC:7127, ENSG00000076242, Entrez 4292, OMIM 120436
Location	Chr3:36,993,226-37,050,896 (+ strand, 3p22.2)
Transcripts	44 Ensembl, MANE Select: NM_000249
Protein	P40692 (756 aa, 84.6 kDa)
Structures	7 PDB entries, AlphaFold model (pLDDT 77.89)
Orthologs	Conserved across mouse, rat, zebrafish, fly, worm, yeast
ClinVar Variants	6,260 total (500+ pathogenic)
AlphaMissense	4,981 missense predictions
SpliceAI	2,888 splice effect predictions
Pathways	6 Reactome (mismatch repair, meiosis, TP53 regulation)
GO Terms	35 (DNA repair, meiosis, ATP binding)
Interactions	3,428+ STRING, 514+ IntAct
Expression	Ubiquitous (highest in muscle, heart, germline)
Primary Diseases	Lynch syndrome (definitive), Muir-Torre syndrome, CMMRD
Pharmacogenomics	VIP gene - affects platinum compound response