• Gene id: 4292

Gene Summary

• Gene Symbol: MLH1   Gene   UCSC   Ensembl
• Aliases: COCA2, FCC2, HNPCC, HNPCC2, hMLH1
• Gene name: mutL homolog 1
• Alternate names: DNA mismatch repair protein Mlh1, mutL homolog 1, colon cancer, nonpolyposis type 2,
• Gene location: 3p22.2 (36993349: 37050845)     Exons: 21     NC_000003.12
• Gene summary(Entrez): 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 introd
• OMIM: 120436

SNPs

rs9852810

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000003.12   g.37027478G>A
NC_000003.11   g.37068969G>A
NG_007109.2   g.39129G>A|SEQ=[G/A]|GENE=MLH1

rs4647269

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000003.12   g.37016100C>T
NC_000003.11   g.37057591C>T
NG_007109.2   g.27751C>T|SEQ=[C/T]|GENE=MLH1

rs1800734

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000003.12   g.36993455G>A
NC_000003.12   g.36993455G>C
NC_000003.11   g.37034946G>A
NC_000003.11   g.37034946G>C
NG_007109.2   g.5106G>A
NG_007109.2   g.5106G>C
NM_000249.3   c.-93G>A
NM_000249.3   c.-93G>C
NM_001258274.2   c.-1188G>A
NM_001258274.2   c.-1188G>C
NM_0  

Protein Summary

• Protein general information: P40692  
  • Name: DNA mismatch repair protein Mlh1 (MutL protein homolog 1)
  • Length: 756  
  • Mass: 84,601
• Sequence:

  MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDI
  VCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQI
  TVEDLFYNIATRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRSIFGNAVS
  RELIEIGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISP
  QNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGSNSSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSS
  DKVYAHQMVRTDSREQKLDAFLQPLSKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGD
  TTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLSLQEEINEQGHEVLREML
  HNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESGWTEE
  DGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILRLATEVNWDEEKECFES
  LSKECAMFYSIRKQYISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLY
  KVFERC

• Structural information:
  • Interpro: IPR013507  IPR014762  IPR002099  IPR011186  IPR003594   IPR036890  IPR032189  IPR020568  IPR014721  
  • Prosite: PS00058
  • CDD: cd00075
  • PDB: 3RBN 4P7A
  • PDBsum: 3RBN 4P7A
  • DIP: 27601
  • STRING: ENSP00000231790
• Other Databases: GeneCards:  MLH1  Malacards:  MLH1

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000289	nuclear-transcribed mRNA poly(A) tail shortening	IEA	biological process
GO:0000712	resolution of meiotic recombination intermediates	IEA	biological process
GO:0000795	synaptonemal complex	IBA	cellular component
GO:0001673	male germ cell nucleus	IEA	cellular component
GO:0003682	chromatin binding	IEA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005634	nucleus	IC	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005712	chiasma	IBA	cellular component
GO:0006298	mismatch repair	IGI	biological process
GO:0006298	mismatch repair	TAS	biological process
GO:0006303	double-strand break repair via nonhomologous end joining	IEA	biological process
GO:0007060	male meiosis chromosome segregation	IEA	biological process
GO:0007129	synapsis	IEA	biological process
GO:0007283	spermatogenesis	IEA	biological process
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage	IEA	biological process
GO:0016020	membrane	IDA	cellular component
GO:0016321	female meiosis chromosome segregation	IEA	biological process
GO:0016446	somatic hypermutation of immunoglobulin genes	IBA	biological process
GO:0016887	ATPase activity	IBA	molecular function
GO:0032137	guanine/thymine mispair binding	IEA	molecular function
GO:0032389	MutLalpha complex	IBA	cellular component
GO:0043060	meiotic metaphase I plate congression	IEA	biological process
GO:0045141	meiotic telomere clustering	IEA	biological process
GO:0045190	isotype switching	IEA	biological process
GO:0045950	negative regulation of mitotic recombination	IEA	biological process
GO:0048477	oogenesis	IEA	biological process
GO:0051257	meiotic spindle midzone assembly	IEA	biological process
GO:0003697	single-stranded DNA binding	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0032407	MutSalpha complex binding	IDA	molecular function
GO:0000289	nuclear-transcribed mRNA poly(A) tail shortening	IEA	biological process
GO:0000712	resolution of meiotic recombination intermediates	IEA	biological process
GO:0000793	condensed chromosome	IEA	cellular component
GO:0000794	condensed nuclear chromosome	IEA	cellular component
GO:0000795	synaptonemal complex	IEA	cellular component
GO:0000795	synaptonemal complex	IBA	cellular component
GO:0001673	male germ cell nucleus	IEA	cellular component
GO:0002204	somatic recombination of immunoglobulin genes involved in immune response	IEA	biological process
GO:0003682	chromatin binding	IEA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IC	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005694	chromosome	IEA	cellular component
GO:0005712	chiasma	IEA	cellular component
GO:0005712	chiasma	IBA	cellular component
GO:0006281	DNA repair	IEA	biological process
GO:0006281	DNA repair	IEA	biological process
GO:0006298	mismatch repair	IEA	biological process
GO:0006298	mismatch repair	IEA	biological process
GO:0006298	mismatch repair	IGI	biological process
GO:0006298	mismatch repair	TAS	biological process
GO:0006298	mismatch repair	TAS	biological process
GO:0006303	double-strand break repair via nonhomologous end joining	IEA	biological process
GO:0006974	cellular response to DNA damage stimulus	IEA	biological process
GO:0006974	cellular response to DNA damage stimulus	IEA	biological process
GO:0007049	cell cycle	IEA	biological process
GO:0007060	male meiosis chromosome segregation	IEA	biological process
GO:0007126	meiotic nuclear division	IEA	biological process
GO:0007129	synapsis	IEA	biological process
GO:0007131	reciprocal meiotic recombination	IEA	biological process
GO:0007140	male meiosis	IEA	biological process
GO:0007283	spermatogenesis	IEA	biological process
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage	IEA	biological process
GO:0016020	membrane	IDA	cellular component
GO:0016321	female meiosis chromosome segregation	IEA	biological process
GO:0016446	somatic hypermutation of immunoglobulin genes	IEA	biological process
GO:0016446	somatic hypermutation of immunoglobulin genes	IBA	biological process
GO:0016447	somatic recombination of immunoglobulin gene segments	IEA	biological process
GO:0016887	ATPase activity	IBA	molecular function
GO:0030983	mismatched DNA binding	IEA	molecular function
GO:0032137	guanine/thymine mispair binding	IEA	molecular function
GO:0032389	MutLalpha complex	IEA	cellular component
GO:0032389	MutLalpha complex	IBA	cellular component
GO:0043060	meiotic metaphase I plate congression	IEA	biological process
GO:0045132	meiotic chromosome segregation	IEA	biological process
GO:0045141	meiotic telomere clustering	IEA	biological process
GO:0045143	homologous chromosome segregation	IEA	biological process
GO:0045190	isotype switching	IEA	biological process
GO:0045950	negative regulation of mitotic recombination	IEA	biological process
GO:0048477	oogenesis	IEA	biological process
GO:0051257	meiotic spindle midzone assembly	IEA	biological process
GO:0003697	single-stranded DNA binding	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0032407	MutSalpha complex binding	IDA	molecular function
GO:0000795	synaptonemal complex	IBA	cellular component
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IC	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005712	chiasma	IBA	cellular component
GO:0006298	mismatch repair	IGI	biological process
GO:0006298	mismatch repair	TAS	biological process
GO:0006298	mismatch repair	TAS	biological process
GO:0016020	membrane	IDA	cellular component
GO:0016446	somatic hypermutation of immunoglobulin genes	IBA	biological process
GO:0016887	ATPase activity	IBA	molecular function
GO:0032389	MutLalpha complex	IBA	cellular component
GO:0003697	single-stranded DNA binding	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0032407	MutSalpha complex binding	IDA	molecular function

KEGG pathways

Pathway id	Pathway name
hsa05200	Pathways in cancer
hsa05210	Colorectal cancer
hsa05226	Gastric cancer
hsa05213	Endometrial cancer
hsa01524	Platinum drug resistance

Diseases

Associated diseases	References
Cancer (pancreatic)	GAD: 19351817
Cancer (Adenocarcinoma)	GAD: 18683134
Cancer (gastric)	GAD: 18713157
Cancer (epithelial ovarian)	GAD: 19064572
Cancer (bladder)	GAD: 19237606
Cancer (prostate)	GAD: 15583422
Colorectal cancer	KEGG: H00020
Cancer (endometrial)	KEGG: H00026
Cancer (ovarian)	KEGG: H00027
Colorectal cancer	OMIM: 120436
Cancer	GAD: 20056646
Cancer (leukemia)	GAD: 14510941
Cancer (liver)	GAD: 16172101
Cancer (colorectal)	GAD: 16237223
Cancer (endometrial)	GAD: 14645426
Cancer (stomach)	GAD: 14574163
Cancer (lung)	GAD: 15382050
Cancer (colon)	GAD: 8145827
Cancer	GAD: 18481196
Cancer (melanoma)	GAD: 19741564
Cancer (esophageal)	GAD: 20453000
Cancer (Papilary)	GAD: 20450746
Cancer (Squamous cell)	GAD: 18199718
Cancer (Renal cell)	GAD: 18325052
Cancer (ovarian)	GAD: 16774946
Cancer (lymphoma)	GAD: 18830263
Cancer (thyroid)	GAD: 19730683
Cancer (breast)	GAD: 15958648
Lynch syndrome	GAD: 17224235
Muir-Torre syndrome	OMIM: 120436
Chronic ulcerative colitis	GAD: 15626886
Retinal function	GAD: 12920342
Hodgkin disease	GAD: 17959715
Crohn's disease	GAD: 9230812
Inflammatory bowel disease	GAD: 12011151
Ulcerative colitis	GAD: 19371218
Ulcerative colitis	GAD: 19371218
Crohn's disease	GAD: 9230812
Inflammatory bowel disease	GAD: 12011151
Endometriosis	INFBASE: 24018808
Endometriosis	INFBASE: 12402310
Adenomyosis	INFBASE: 11078826
Ovarian endometriosis	INFBASE: 21556900
Female infertility	INFBASE: 11078826
Azoospermia	MIK: 22594646
Impaired human spermatogenesis	MIK: 20075417
Azoospermia	MIK: 26086992
Male factor infertility	MIK: 19246465
Sperm DNA damage	MIK: 22594646
Sperm DNA damage	MIK: 22594646
Sperm maturation arrest	MIK: 22344730
Maturation arrest	MIK: 22344730
Azoospermia	MIK: 12569174
Oligozoospermia	MIK: 22594646
Oligozoospermia	MIK: 26086992
Sertoli cell only syndrome (SCOS)	MIK: 12569174
Sertoli cell only syndrome (SCOS)	MIK: 12569174
Azoospermia or oligozoospermia	MIK: 26086992
Impaired human spermatogenesis	MIK: 20075417
Azoospermia	MIK: 12569174
Chronic obstructive pulmonary disease (COPD)	GAD: 19625176
Chronic obstructive pulmonary disease (COPD)	GAD: 19625176
Mismatch repair deficiency	KEGG: H00876
Mismatch repair cancer syndrome	OMIM: 120436
Chronic renal failure	GAD: 21085059
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Associated with spermatogenesis and epigenetic regulation	MIK: 21674046
Azoospermia	MIK: 12569174
Sertoli cell-only syndrome	MIK: 12569174
Hypospermatogenesis	MIK: 28361989
Spermatogenic defects	MIK: 20075417
Male infertility	MIK: 19246465
Azoospermia	MIK: 26086992
Oligozoospermia	MIK: 26086992
Maturation arrest	MIK: 22344730
Sperm DNA damage	MIK: 22594646
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
22594646	Sperm DNA damage, Male infertility, azoospermia, oligozoospermia	MLH1 (rs4647269), PMS2 (rs1059060, Ser775Asn), MSH5 (rs2075789, Pro29Ser)	Chinese	1772 (1,292 idiopathic infertility patients, 480 fertile controls)	Male infertility	MLH1 MLH3 PMS2 MSH4 and MSH5
20075417	Impaired human spermatogenesis			28 (13 patients with spermatogenic failure, 5 patients with primary germ cell tumors, 10 controls with conserved spermatogenesis)	Male infertility	MLH1 MLH3 PMS2 MSH4 and MSH5 ATR HSPA2 and SYCP3
19246465	Male infertility			15 (5 control men and 10 infertile men)	Male infertility
26086992	Male infertility, Azoospermia, oligozoospermia	rs6525433, rs175080, rs6525433-rs4844247, and rs1800734-rs175080	China	614 (316 patients (244 men with azoospermia, 72 men with oligozoospermia), 298 controls)	Male infertility	TEX11 TEX15  MLH1 and MLH3
22344730	Maturation arrest	2531C/T-IVS9 + 66G/A			Male infertility	MLH1 MLH3 PMS2
12569174	Azoospermia, Sertoli cell-only syndrome			61 (41 testicular failure patients, 20 controls)	Male infertility	MSH2 MLH1
28983945	Oligozoospermia, Male infertility			39 (10 oligozoospermia, 29 normozoospermia patients)	Male infertility
17327269	Teratozoospermia			13 (5 controls, 8 cases)	Male infertility	GSE6967 analyzed by GEO2R (cutoff 1.5 fold)
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
21674046	Associated with spermatogenesis and epigenetic regulation			18	Male infertility	GSE26881
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881
28361989	Hypospermatogenesis			6 (3 controls, 3 Klienfelter syndrome	Male infertility	Microarray