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FLASH GENE

Symbol

MLH1

contributors: mct - updated : 15-09-2016

HGNC name	mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
HGNC id	7127

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMMRD constitutional mismatch repair-deficiency syndrome HNPCC2 hereditary non polyposis colorectal cancer, type 2 MTS2 Muir-Torre syndrome
Location	3p22.2      Physical location : 37.034.840 - 37.092.335
Synonym name	DNA mismatch repair protein Mlh1
	MutL protein homolog 1
Synonym symbol(s)	COCA2, HNPCC, FCC2, hMLH1, HNPCC, MGC5172

DNA

TYPE	functioning gene
STRUCTURE	57.50 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   enhancer
text structure	promoter contains multiple redundant enhancer elements capable of independent promoter activation
	MLH1 promoter is bi-directional with the EPM2AIP1 gene located on the antisense strand

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	several spliced isoforms expressed in monocytes, normal colon mucosa (PMID: 10573010)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000249 19 - 2662 NP_000240 84.5 756 - 2009 19075283 NM_001167617 19 - 2473 NP_001161089 - 658 - - NM_001167618 19 - 2473 NP_001161090 - 515 - - NM_001167619 18 - 2386 NP_001161091 - 515 - -

EXPRESSION

Type	ubiquitous

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive esophagus       highly Endocrine neuroendocrine pituitary     highly   thyroid         Lymphoid/Immune tonsils       highly Reproductive female system breast mammary gland   highly   male system testis         male system prostate       Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial absorptive excretory digestive epithelium     Epithelial barrier/lining uroepithelium     Epithelial secretory glandular exocrine

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	region of homology with other MutS or MutL homologs, comprising a region of 150 aminoacids
	a putative helix-turn-helix domain associated with an adenine nucleotide and magnesium binding site

mono polymer

heteromer , dimer

HOMOLOGY

interspecies

homolog to yeast mutator gene (bacterial mutL)

Homologene

FAMILY

DNA mismatch repair mutL/hexB family

CATEGORY

DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	correcting of base-base mismatches and insertion-deletion loops resulting from DNA replication and recombination events
	possessing an intrinsic low-level ATPase activity
	TEX11, testis expressed gene 15 (TEX15), mutL homolog 1 (MLH1), and homolog 3 (MLH3), play critical roles in genome integrity, meiotic recombination, and gametogenesis

CELLULAR PROCESS	cell cycle
	nucleotide, repair, mismatch repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

mismatch repair

a component	heterodimers with MLH3, PMS1, PMS2
	part of the BRCA1-associated genome surveillance complex (BASC)

INTERACTION

DNA	binding to GT mispairs

RNA

small molecule	nucleotide,
	ATP

protein	PMS2, MLH3, PhS1, NF1
	MLH1-MLH3, a meiotic crossover and DNA mismatch repair factor, is a MSH2-MSH3-stimulated endonuclease

cell & other

REGULATION

inhibited by

promoter hypermethylation

ASSOCIATED DISORDERS

corresponding disease(s)

HNPCC2 , MTS2 , CMMRD

related resource

InternationalGrouponHereditaryNon-PolyposisColorectalCancer

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       loss of function in colon and uterus tumor tumoral germinal mutation       in the 3'-untranslated region (3'-UTR) leads to DNA mismatch repair deficiency, conferring leukemia relapse tumoral   deletion     in early and late-onset breast carcinoma tumoral     --low   by promoter methylation, associated with poor prognosis in non-small cell lung carcinoma

Susceptibility

to inflammatory bowel disease (Crohn, ulcerative colitis) to prostate cancer

Variant & Polymorphism other	a protective role for the codon 384 variant allele against prostate cancer
	rare genetic variants that confer a high risk of prostate cancer when mutated

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS