Reviewed, UniProtKB/Swiss-Prot P40692 (MLH1_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA mismatch repair protein Mlh1
Alternative name(s):
    MutL protein homolog 1

Gene names

Name:	MLH1
Synonyms:	COCA2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis. Ref.14 Ref.15
Subunit structure	Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MBD4. Interacts with EXO1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Nucleus. Ref.10 Ref.12
Tissue specificity	Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.
Involvement in disease	Defects in MLH1 are the cause of hereditary non-polyposis colorectal cancer type 2 (HNPCC2) [MIM:609310]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. Ref.9 Ref.4 Ref.5 Ref.13 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.36 Ref.38 Ref.39 Ref.41 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.59 Ref.62 Ref.64 Ref.65 Ref.66 Ref.67 Ref.69 Ref.70 Ref.71 Ref.72 Ref.73 Ref.74 Ref.75 Ref.76 Ref.78 Ref.80 Ref.81 Ref.82 Ref.84 Ref.85 Ref.87 Ref.89 Ref.90 Ref.92 Ref.93 Ref.95 Defects in MLH1 are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:276300]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots. Ref.9 Ref.13 Ref.21 Ref.91 Defects in MLH1 are a cause of Muir-Torre syndrome (MTS) [MIM:158320]. MTS is a rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. Ref.13 Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast. Ref.13 Ref.60 Defects in MLH1 are a cause of susceptibility to endometrial cancer [MIM:608089]. Ref.13 Some epigenetic changes can be transmitted unchanged through the germline (termed 'epigenetic inheritance'). Evidence that this mechanism occurs in humans is provided by the identification of individuals in whom 1 allele of the MLH1 gene is epigenetically silenced throughout the soma (implying a germline event). These individuals are affected by HNPCC but does not have identifiable mutations in MLH1, even though it is silenced, which demonstrats that an epimutation can phenocopy a genetic disease. Ref.13
Sequence similarities	Belongs to the DNA mismatch repair mutL/hexB family.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary nonpolyposis colorectal cancer Tumor suppressor
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW mismatch repair Ref.2 Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred by curator. Source: HGNC
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro mismatched DNA binding Inferred from electronic annotation. Source: InterPro protein binding Ref.9 Ref.10 Ref.12 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PMS2	P54278	1	EBI-744248,EBI-1162561
TMSB4X	P62328	1	EBI-744248,EBI-712598
ZC3H11A	O75152	2	EBI-744248,EBI-748480

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 756	756	DNA mismatch repair protein Mlh1		PRO_0000178000
Regions
	Region	410 – 650	241	Interaction with EXO1
Amino acid modifications
	Modified residue	477	1	Phosphoserine Ref.19
Natural variations
	Natural variant	18	1	R → C in HNPCC2. Ref.80		VAR_022663
	Natural variant	19	1	I → F in HNPCC2; uncertain pathogenicity. Ref.75		VAR_043383
	Natural variant	21	1	A → V in HNPCC2. Ref.85		VAR_043384
	Natural variant	22	1	G → A: dbSNP rs41295280. Ref.94		VAR_038023
	Natural variant	25	1	I → F in HNPCC2. Ref.53		VAR_043385
	Natural variant	28	1	P → L in HNPCC2. Ref.35 Ref.50 Ref.75 Ref.89 Ref.90		VAR_004433
	Natural variant	29	1	A → S in HNPCC2; could be a polymorphism; has no effect on ex vivo splicing assay. Ref.76 Ref.89		VAR_043386
	Natural variant	32	1	I → V: dbSNP rs2020872. Ref.5		VAR_014876
	Natural variant	35	1	M → K in HNPCC2; uncertain pathogenicity. Ref.90		VAR_043387
	Natural variant	35	1	M → N in MMRCS; requires 2 nucleotide substitutions. Ref.67 Ref.91		VAR_043388
	Natural variant	35	1	M → R in HNPCC2.		VAR_004434
	Natural variant	37	1	E → ELNH in endometrial cancer; somatic mutation.		VAR_004435
	Natural variant	38	1	N → H in HNPCC2. Ref.67		VAR_043389
	Natural variant	41	1	D → G in HNPCC2. Ref.84		VAR_043390
	Natural variant	41	1	D → H Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054522
	Natural variant	44	1	S → F in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.38		VAR_004436
	Natural variant	45 – 47	3	TSI → CF in HNPCC2.		VAR_043391
	Natural variant	54	1	G → E in CRC; sporadic; somatic mutation. Ref.29		VAR_012902
	Natural variant	62	1	Q → K in HNPCC2; reduced repair efficiency in a yeast mismatch repair assay. Ref.27		VAR_004437
	Natural variant	63	1	D → E in HNPCC2. Ref.89		VAR_043392
	Natural variant	64	1	N → S in HNPCC2. Ref.27		VAR_004438
	Natural variant	67	1	G → E in CRC. Ref.94		VAR_038024
	Natural variant	67	1	G → R in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.33 Ref.46 Ref.47 Ref.76 Ref.85 Ref.89 Ref.90 Ref.95		VAR_004439
	Natural variant	67	1	G → W in HNPCC2. Ref.48 Ref.51		VAR_012903
	Natural variant	68	1	I → N in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay. Ref.85		VAR_004440
	Natural variant	69	1	R → K in HNPCC2; reduced repair efficiency in a mismatch repair assay. Ref.43		VAR_004441
	Natural variant	71	1	Missing in HNPCC2.		VAR_043393
	Natural variant	77	1	C → R in HNPCC2 and CRC; sporadic; normal interaction with PMS2; loss of function in a mismatch repair assay. Ref.44 Ref.71 Ref.89 Ref.95		VAR_004442
	Natural variant	77	1	C → Y in CRC; sporadic; early onset. Ref.37		VAR_012904
	Natural variant	80	1	F → V in HNPCC2. Ref.62 Ref.89		VAR_012905
	Natural variant	84	1	K → E in HNPCC2. Ref.50 Ref.89		VAR_012906
	Natural variant	93	1	S → G Common polymorphism; normal interaction with PMS2; no functional alteration detected by an in vitro mismatch repair assay. dbSNP rs41295282. Ref.45 Ref.71 Ref.89 Ref.94		VAR_004443
	Natural variant	98	1	G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054523
	Natural variant	101	1	G → D in HNPCC2; has no effect on ex vivo splicing assay. Ref.80 Ref.95		VAR_022664
	Natural variant	101	1	G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054524
	Natural variant	102	1	E → K in HNPCC2; uncertain pathogenicity. Ref.92		VAR_043394
	Natural variant	106	1	S → R in gastric cancer; uncertain pathogenicity. Ref.59		VAR_043395
	Natural variant	107	1	I → R in HNPCC2; normal interaction with PMS2; loss of function in a mismatch repair assay. Ref.71 Ref.89		VAR_004444
	Natural variant	109	1	H → Q in gastric cancer; uncertain pathogenicity. Ref.59		VAR_043396
	Natural variant	111	1	A → V in HNPCC2; uncertain pathogenicity. Ref.55 Ref.90		VAR_012907
	Natural variant	116	1	T → K Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054525
	Natural variant	117	1	T → M in HNPCC2; fails to interact with PMS2 and EXO1; loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.10 Ref.23 Ref.51 Ref.67 Ref.69 Ref.73 Ref.75 Ref.90 Ref.95		VAR_004445
	Natural variant	117	1	T → R in HNPCC2; equivalent substitution in yeast causes loss of function in mismatch repair assay. Ref.47		VAR_004446
	Natural variant	126	1	Y → N Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054526
	Natural variant	128	1	A → P in HNPCC2. Ref.30		VAR_012908
	Natural variant	132	1	D → H in CRC; sporadic; susceptibility to; ATPase function attenuated but not eliminated. Ref.88		VAR_022665
	Natural variant	155	1	L → R in HNPCC2. Ref.89		VAR_043397
	Natural variant	182	1	R → G in HNPCC2; incomplete. Ref.36 Ref.51		VAR_012909
	Natural variant	182	1	R → K in HNPCC2. Ref.80		VAR_022666
	Natural variant	185	1	V → G in HNPCC2; defective in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.69 Ref.89		VAR_004447
	Natural variant	185	1	V → L in HNPCC2; could be a polymorphism. Ref.76		VAR_043398
	Natural variant	193	1	S → P in HNPCC2. Ref.44		VAR_004448
	Natural variant	213	1	V → M Associated with HNPCC2; has no effect on ex vivo splicing assay. dbSNP rs2308317. Ref.5 Ref.56 Ref.70 Ref.89 Ref.95		VAR_012910
	Natural variant	215	1	N → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054527
	Natural variant	216	1	I → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054528
	Natural variant	217	1	R → C in HNPCC2; could be a polymorphism; proficient in a mismatch repair assay. dbSNP rs4986984. Ref.25 Ref.41 Ref.69 Ref.82		VAR_004449
	Natural variant	217	1	R → G		VAR_020469
	Natural variant	219	1	I → V Common polymorphism; found in 37% of alleles. dbSNP rs1799977. Ref.5 Ref.30 Ref.33 Ref.46 Ref.47 Ref.55 Ref.69 Ref.72 Ref.73 Ref.75 Ref.89 Ref.29 Ref.37 Ref.68		VAR_004450
	Natural variant	226 – 295	70	Missing in HNPCC2.		VAR_004452
	Natural variant	226	1	R → L in HNPCC2. Ref.23		VAR_004451
	Natural variant	234	1	E → G in HNPCC2; uncertain pathogenicity. Ref.59		VAR_043399
	Natural variant	244	1	G → D in HNPCC2; defective in a mismatch repair assay. Ref.30 Ref.69 Ref.76		VAR_012911
	Natural variant	244	1	G → V in CRC; sporadic; somatic mutation; could be a polymorphism. Ref.29		VAR_012912
	Natural variant	247	1	S → P in HNPCC2. Ref.73 Ref.89		VAR_043400
	Natural variant	260	1	L → F Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054529
	Natural variant	260	1	L → R in CRC. Ref.57		VAR_043401
	Natural variant	262	1	Missing in HNPCC2.		VAR_012913
	Natural variant	264	1	H → Y in HNPCC2. Ref.54		VAR_043402
	Natural variant	265	1	R → C Associated with HNPCC2; results in partial exon 10 skipping on ex vivo splicing assay. Ref.95		VAR_054530
	Natural variant	265	1	R → H Rare polymorphism; associated with HNPCC2; slightly lower mismatch repair efficiency; results in partial exon 10 skipping on ex vivo splicing assay. Ref.28 Ref.69 Ref.95 Ref.49		VAR_012914
	Natural variant	268	1	E → G in CRC. Ref.40		VAR_012915
	Natural variant	282	1	A → G in HNPCC2. Ref.82		VAR_043403
	Natural variant	292	1	L → P in HNPCC2; uncertain pathogenicity. Ref.75 Ref.90		VAR_043404
	Natural variant	295	1	S → T in HNPCC2. Ref.36		VAR_012916
	Natural variant	304	1	D → V in HNPCC2. Ref.57		VAR_043405
	Natural variant	309	1	P → S		VAR_038025
	Natural variant	320	1	E → D Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054531
	Natural variant	321	1	S → I in HNPCC2; uncertain pathogenicity. Ref.59		VAR_043406
	Natural variant	325 – 327	3	Missing in colorectal cancer.		VAR_043407
	Natural variant	325	1	R → Q in CRC; sporadic; somatic mutation; could be a polymorphism. Ref.29		VAR_012917
	Natural variant	326	1	V → A in HNPCC2; proficient in a mismatch repair assay. Ref.69 Ref.95 Ref.49		VAR_004453
	Natural variant	329	1	H → P in HNPCC2. Ref.32 Ref.50 Ref.62 Ref.89		VAR_012918
	Natural variant	330	1	Missing in HNPCC2; results in weak exon 11 skipping on ex vivo splicing assay.		VAR_043408
	Natural variant	338	1	N → S in HNPCC2. Ref.66		VAR_043409
	Natural variant	379	1	Y → C in HNPCC2. Ref.80		VAR_022667
	Natural variant	384	1	V → D Could be a non-fonctional polymorphism associated with HNPCC confined to East Asian population. Ref.55 Ref.26 Ref.42		VAR_004454
	Natural variant	385	1	R → C in HNPCC2; uncertain pathogenicity. Ref.70		VAR_043410
	Natural variant	385	1	R → P in HNPCC2; uncertain pathogenicity. Ref.49		VAR_043411
	Natural variant	406	1	S → N: dbSNP rs41294980. Ref.94 Ref.29 Ref.49		VAR_012919
	Natural variant	441	1	A → T in HNPCC2. Ref.38 Ref.90		VAR_012920
	Natural variant	443	1	K → Q: dbSNP rs34213726. Ref.89		VAR_043412
	Natural variant	472	1	R → I in CRC; uncertain pathogenicity. Ref.59		VAR_043413
	Natural variant	474	1	R → Q in HNPCC2; has no effect on ex vivo splicing assay; uncertain pathogenicity. Ref.92 Ref.95		VAR_043414
	Natural variant	474	1	R → W Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054532
	Natural variant	485	1	D → E in HNPCC2. Ref.47		VAR_043415
	Natural variant	485	1	D → H in HNPCC2; uncertain pathogenicity. Ref.59		VAR_043416
	Natural variant	492	1	A → T in HNPCC2 and CRC; sporadic. Ref.24		VAR_004455
	Natural variant	506	1	V → A in HNPCC2.		VAR_004456
	Natural variant	539	1	A → D Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054533
	Natural variant	542	1	Q → L in HNPCC2; type II; equivalent substitution in yeast causes loss of function in a mismatch repair assay. Ref.4 Ref.25 Ref.82		VAR_004457
	Natural variant	542	1	Q → P in HNPCC2. Ref.82		VAR_043417
	Natural variant	549	1	L → P in HNPCC2; has no effect on ex vivo splicing assay. Ref.25 Ref.82 Ref.95		VAR_012921
	Natural variant	550	1	L → P in HNPCC2. Ref.89		VAR_043418
	Natural variant	551	1	N → T in HNPCC2; has no effect on ex vivo splicing assay. Ref.36 Ref.46 Ref.95		VAR_012922
	Natural variant	559	1	L → R in HNPCC2. Ref.80		VAR_022668
	Natural variant	565	1	I → F in HNPCC2. Ref.46		VAR_012923
	Natural variant	574	1	L → P in HNPCC2; type I; abrogates interaction with EXO1. Ref.9 Ref.4 Ref.25 Ref.82		VAR_004458
	Natural variant	578	1	E → G in HNPCC2 and CRC. Ref.52		VAR_004459
	Natural variant	582	1	L → V in HNPCC2; type II. Ref.4		VAR_004460
	Natural variant	585	1	L → R Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054534
	Natural variant	586	1	A → P in HNPCC2. Ref.78		VAR_015689
	Natural variant	588	1	L → P in HNPCC2. Ref.55		VAR_012924
	Natural variant	589	1	A → D in HNPCC2. Ref.89		VAR_043419
	Natural variant	596	1	Missing in HNPCC2.		VAR_043420
	Natural variant	601	1	D → G in CRC; uncertain pathogenicity. Ref.79		VAR_043421
	Natural variant	603	1	P → R in HNPCC2; suspected; could be a polymorphism; has no effect on ex vivo splicing assay. dbSNP rs35831931. Ref.62 Ref.66 Ref.95		VAR_012925
	Natural variant	607	1	L → H in LCIS and HNPCC2; could be a polymorphism;; has no effect on ex vivo splicing assay; could determine an increased risk of colon cancer. dbSNP rs41295284. Ref.56 Ref.70 Ref.95 Ref.60 Ref.94		VAR_012926
	Natural variant	612	1	Missing in HNPCC2.		VAR_043422
	Natural variant	616	1	Missing in HNPCC2 and MMRCS; abrogates interaction with EXO1; has no effect on ex vivo splicing assay.		VAR_004461
	Natural variant	618	1	K → A Common polymorphism; requires 2 nucleotide substitutions. Ref.27 Ref.52 Ref.56 Ref.62 Ref.67 Ref.73 Ref.74 Ref.89 Ref.94		VAR_004462
	Natural variant	618	1	K → R in colorectal cancer. Ref.77		VAR_043424
	Natural variant	618	1	K → T in HNPCC2; type II. Ref.4 Ref.24 Ref.66 Ref.70 Ref.89 Ref.49		VAR_004463
	Natural variant	618	1	Missing in HNPCC2.		VAR_043423
	Natural variant	619	1	A → P Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054535
	Natural variant	622	1	L → H in HNPCC2. Ref.65		VAR_012927
	Natural variant	623	1	A → P in HNPCC2; uncertain pathogenicity. Ref.90		VAR_043425
	Natural variant	626 – 627	2	FS → ST in HNPCC2.		VAR_004464
	Natural variant	631	1	D → A in HNPCC2; uncertain pathogenicity. Ref.59		VAR_043426
	Natural variant	635	1	N → K in gastric cancer; uncertain pathogenicity. Ref.59		VAR_043427
	Natural variant	636	1	L → P in HNPCC2. Ref.82		VAR_043428
	Natural variant	640	1	P → L Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054536
	Natural variant	640	1	P → S in HNPCC2; has no effect on ex vivo splicing assay. Ref.82 Ref.95		VAR_043429
	Natural variant	646	1	Y → C in HNPCC2; could be a common polymorphism. dbSNP rs35045067. Ref.74 Ref.89		VAR_043430
	Natural variant	648	1	P → L in HNPCC2. Ref.62 Ref.89		VAR_012928
	Natural variant	648	1	P → S in HNPCC2; protein unstable but still functional in mismatch repair. Ref.70 Ref.81 Ref.89		VAR_022669
	Natural variant	654	1	P → L in HNPCC2. Ref.89		VAR_043431
	Natural variant	655	1	I → V in endometrial cancer; also associated with HNPCC2; has no effect on ex vivo splicing assay. dbSNP rs55907433. Ref.95 Ref.68		VAR_043432
	Natural variant	656	1	F → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054537
	Natural variant	657	1	Missing in HNPCC2; uncertain pathogenicity.		VAR_043433
	Natural variant	659	1	R → L in HNPCC2. Ref.9 Ref.56		VAR_012929
	Natural variant	659	1	R → P in HNPCC2; interacts only very weakly with PMS2; equivalent substitution in yeast causes almost complete loss of function in a mismatch repair assay; abrogates interaction with EXO1. Ref.27 Ref.71 Ref.89		VAR_004465
	Natural variant	659	1	R → Q		VAR_043434
	Natural variant	662	1	T → P in HNPCC2; could be a rare polymorphism. Ref.62 Ref.72		VAR_012930
	Natural variant	666	1	W → R Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.95		VAR_054538
	Natural variant	681	1	A → T in HNPCC2; could be a common polymorphism; equivalent substitution in yeast does not affect mismatch repair; abrogates interaction with EXO1. Ref.9 Ref.75 Ref.89 Ref.90 Ref.95 Ref.94		VAR_004466
	Natural variant	687	1	R → W in HNPCC2; uncertain pathogenicity. Ref.65 Ref.75 Ref.90		VAR_012931
	Natural variant	689	1	Q → R in HNPCC; suspected; could be a polymorphism. Ref.62 Ref.95 Ref.94		VAR_012932
	Natural variant	716	1	V → M: dbSNP rs35831931. Ref.46 Ref.62 Ref.73 Ref.89 Ref.94 Ref.49		VAR_012933
	Natural variant	718	1	H → Y in HNPCC2; could be a polymorphism. dbSNP rs2020873. Ref.53 Ref.66 Ref.94		VAR_004467
	Natural variant	719	1	I → INVFHI in HNPCC2.		VAR_043435
	Natural variant	724	1	L → M in HNPCC2. Ref.82		VAR_043436
	Natural variant	729	1	L → V: dbSNP rs1800149.		VAR_004468
	Natural variant	749	1	L → P in colorectal cancer. Ref.77		VAR_043437
	Natural variant	751	1	K → R in HNPCC2; could be a polymorphism. Ref.64 Ref.90 Ref.94		VAR_012934
	Natural variant	755	1	R → W in HNPCC; incomplete. Ref.51		VAR_012935
Experimental info
	Sequence conflict	708 – 711	4	Missing in AAA85687. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P40692-1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: C9231FC406C2CA20	FASTA	756	84,601
	10 20 30 40 50 60 MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI VKEGGLKLIQ 70 80 90 100 110 120 IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR GEALASISHV AHVTITTKTA 130 140 150 160 170 180 DGKCAYRASY SDGKLKAPPK PCAGNQGTQI TVEDLFYNIA TRRKALKNPS EEYGKILEVV 190 200 210 220 230 240 GRYSVHNAGI SFSVKKQGET VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF 250 260 270 280 290 300 KMNGYISNAN YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP 310 320 330 340 350 360 QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEMV 370 380 390 400 410 420 KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL SKPLSSQPQA IVTEDKTDIS 430 440 450 460 470 480 SGRARQQDEE MLELPAPAEV AAKNQSLEGD TTKGTSEMSE KRGPTSSNPR KRHREDSDVE 490 500 510 520 530 540 MVEDDSRKEM TAACTPRRRI INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL 550 560 570 580 590 600 AQHQTKLYLL NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE 610 620 630 640 650 660 DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL EGLPIFILRL 670 680 690 700 710 720 ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ QSEVPGSIPN SWKWTVEHIV 730 740 750 YKALRSHILP PKHFTEDGNI LQLANLPDLY KVFERC

References

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[1]	"Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer." Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K., Kane M.F., Earibino C., Lipford J., Lindblom A., Tannergaard P., Bollag R.J., Godwin A.R., Ward D.C., Nordenskjoeld M., Fishel R., Kolodner R.D., Liskay R.M. Nature 368:258-261(1994) [PubMed: 8145827] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mutation of a mutL homolog in hereditary colon cancer." Papadopoulos N., Nicolaides N.C., Wei Y.-F., Ruben S.M., Carter K.C., Rosen C.A., Haseltine W.A., Fleischmann R.D., Fraser C.M., Adams M.D., Venter J.C., Hamilton S.R., Petersen G.M., Watson P., Lynch H.T., Peltomaeki P., Mecklin J.-P., de la Chapelle A., Kinzler K.W., Vogelstein B. Science 263:1625-1629(1994) [PubMed: 8128251] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Gall bladder.
[3]	"Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations." Kolodner R.D., Hall N.R., Lipford J.R., Kane M.F., Morrison P., Finan P.J., Burn J., Chapman P., Earabino C., Merchant E., Bishop D.T. Cancer Res. 55:242-248(1995) [PubMed: 7812952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC)." Han H.-J., Maruyama M., Baba S., Park J.-G., Nakamura Y. Hum. Mol. Genet. 4:237-242(1995) [PubMed: 7757073] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HNPCC2 LEU-542; PRO-574; VAL-582 AND THR-618.
[5]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HNPCC2 MET-213, VARIANTS VAL-32 AND VAL-219.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	"BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures." Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J. Genes Dev. 14:927-939(2000) [PubMed: 10783165] [Abstract] Cited for: IDENTIFICATION OF MLH1 AS MEMBER OF BASC.
[8]	"MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1." Bellacosa A., Cicchillitti L., Schepis F., Riccio A., Yeung A.T., Matsumoto Y., Golemis E.A., Genuardi M., Neri G. Proc. Natl. Acad. Sci. U.S.A. 96:3969-3974(1999) [PubMed: 10097147] [Abstract] Cited for: INTERACTION WITH MBD4.
[9]	"The interaction of DNA mismatch repair proteins with human exonuclease I." Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R. J. Biol. Chem. 276:33011-33018(2001) [PubMed: 11427529] [Abstract] Cited for: INTERACTION WITH EXO1 AND PMS2, CHARACTERIZATION OF VARIANTS HNPCC2 PRO-574; LYS-616 DEL; LEU-659 AND THR-681, CHARACTERIZATION OF VARIANT MMRCS LYS-616 DEL.
[10]	"HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes." Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C., Rasmussen L.J. Oncogene 20:3590-3595(2001) [PubMed: 11429708] [Abstract] Cited for: INTERACTION WITH EXO1, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT MET-117.
[11]	"Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome." Sun X., Zheng L., Shen B. Cancer Res. 62:6026-6030(2002) [PubMed: 12414623] [Abstract] Cited for: INTERACTION WITH EXO1.
[12]	"Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA." Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J. Oncogene 23:1457-1468(2004) [PubMed: 14676842] [Abstract] Cited for: INTERACTION WITH EXO1, SUBCELLULAR LOCATION.
[13]	"The genetic basis of Muir-Torre syndrome includes the hMLH1 locus." Bapat B., Xia L., Madlensky L., Mitri A., Tonin P., Narod S.A., Gallinger S. Am. J. Hum. Genet. 59:736-739(1996) [PubMed: 8751876] [Abstract] Cited for: DISEASE.
[14]	"Endonucleolytic function of MutLalpha in human mismatch repair." Kadyrov F.A., Dzantiev L., Constantin N., Modrich P. Cell 126:297-308(2006) [PubMed: 16873062] [Abstract] Cited for: FUNCTION.
[15]	"Direct visualization of asymmetric adenine nucleotide-induced conformational changes in MutL alpha." Sacho E.J., Kadyrov F.A., Modrich P., Kunkel T.A., Erie D.A. Mol. Cell 29:112-121(2008) [PubMed: 18206974] [Abstract] Cited for: FUNCTION.
[16]	"Human mismatch repair: reconstitution of a nick-directed bidirectional reaction." Constantin N., Dzantiev L., Kadyrov F.A., Modrich P. J. Biol. Chem. 280:39752-39761(2005) [PubMed: 16188885] [Abstract] Cited for: REVIEW.
[17]	"MutLalpha: at the cutting edge of mismatch repair." Jiricny J. Cell 126:239-241(2006) [PubMed: 16873053] [Abstract] Cited for: REVIEW.
[18]	"Mechanisms and functions of DNA mismatch repair." Li G.M. Cell Res. 18:85-98(2008) [PubMed: 18157157] [Abstract] Cited for: REVIEW.
[19]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, MASS SPECTROMETRY.
[20]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[21]	"The molecular basis of Turcot's syndrome." Hamilton S.R., Liu B., Parsons R.E., Papadopoulos N., Jen J., Powell S.M., Krush A.J., Berk T., Cohen Z., Tetu B., Burger P.C., Wood P.A., Taqi F., Booker S.V., Petersen G.M., Offerhaus G.J.A., Tersmette A.C., Giardiello F.M., Vogelstein B., Kinzler K.W. N. Engl. J. Med. 332:839-847(1995) [PubMed: 7661930] [Abstract] Cited for: VARIANT MMRCS LYS-616 DEL.
[22]	"Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16." Wijnen J., Khan P.M., Vasen H., Menko F., van der Klift H., van den Broek M., van Leeuwen-Cornelisse I., Nagengast F., Meijers-Heijboer E.J., Lindhout D., Griffioen G., Cats A., Kleibeuker J., Varesco L., Bertario L., Bisgaard M.-L., Mohr J., Kolodner R.D., Fodde R. Am. J. Hum. Genet. 58:300-307(1996) [PubMed: 8571956] [Abstract] Cited for: VARIANT HNPCC2 LYS-616 DEL.
[23]	"CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations." Maliaka Y.K., Chudina A.P., Belev N.F., Alday P., Bochkov N.P., Buerstedde J.-M. Hum. Genet. 97:251-255(1996) [PubMed: 8566964] [Abstract] Cited for: VARIANTS HNPCC2 MET-117 AND LEU-226.
[24]	"Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer." Moslein G., Tester D.J., Lindor N.M., Honchel R., Cunningham J.M., French A.J., Halling K.C., Schwab M., Goretzki P., Thibodeau S.N. Hum. Mol. Genet. 5:1245-1252(1996) [PubMed: 8872463] [Abstract] Cited for: VARIANTS HNPCC2 LYS-616 DEL AND THR-618, VARIANT CRC THR-492.
[25]	"Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer." Han H.-J., Yuan Y., Ku J.-L., Oh J.-H., Won Y.-J., Kang K.J., Kim K.Y., Kim S., Kim C.Y., Kim J.-P., Oh N.-G., Lee K.H., Choe K.J., Nakamura Y., Park J.-G. J. Natl. Cancer Inst. 88:1317-1319(1996) [PubMed: 8797773] [Abstract] Cited for: VARIANTS HNPCC2 CYS-217; LEU-542; PRO-549 AND PRO-574.
[26]	"Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability." Kobayashi K., Matsushima M., Koi S., Saito H., Sagae S., Kudo R., Nakamura Y. Jpn. J. Cancer Res. 87:141-145(1996) [PubMed: 8609062] [Abstract] Cited for: VARIANT ENDOMETRIAL CANCER LEU-ASN-HIS-37 INS, VARIANT ASP-384.
[27]	"Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations." Wijnen J., Khan P.M., Vasen H., van der Klift H., Mulder A., van Leeuwen-Cornelisse I., Bakker B., Losekoot M., Moeller P., Fodde R. Am. J. Hum. Genet. 61:329-335(1997) [PubMed: 9311737] [Abstract] Cited for: VARIANTS HNPCC2 LYS-62; SER-64; LYS-616 DEL; ALA-618 AND PRO-659.
[28]	"Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer." Viel A., Genuardi M., Capozzi E., Leonardi F., Bellacosa A., Paravatou-Petsotas M., Pomponi M.G., Fornasarig M., Percesepe A., Roncucci L., Tamassia M.G., Benatti P., Ponz de Leon M., Valenti A., Covino M., Anti M., Foletto M., Boiocchi M., Neri G. Genes Chromosomes Cancer 18:8-18(1997) [PubMed: 8993976] [Abstract] Cited for: VARIANT HNPCC2 LYS-616 DEL, VARIANT HIS-265.
[29]	"MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis." Wu Y., Nystroem-Lahti M., Osinga J., Looman M.W.G., Peltomaeki P., Aaltonen L.A., de la Chapelle A., Hofstra R.M.W., Buys C.H.C.M. Genes Chromosomes Cancer 18:269-278(1997) [PubMed: 9087566] [Abstract] Cited for: VARIANTS CRC GLU-54; VAL-244 AND GLN-325, VARIANTS VAL-219 AND ASN-406.
[30]	"Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes." Pensotti V., Radice P., Presciuttini S., Calistri D., Gazzoli I., Grimalt Perez A.P., Mondini P., Buonsanti G., Sala P., Rossetti C., Ranzani G.N., Bertario L., Pierotti M.A. Genes Chromosomes Cancer 19:135-142(1997) [PubMed: 9218993] [Abstract] Cited for: VARIANTS HNPCC2 PRO-128 AND ASP-244, VARIANT VAL-219.
[31]	"Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria." Beck N.E., Tomlinson I.P.M., Homfray T., Frayling I., Hodgson S.V., Harocopos C.J., Bodmer W.F. Hum. Genet. 99:219-224(1997) [PubMed: 9048925] [Abstract] Cited for: VARIANT HNPCC2 626-SER-THR-627.
[32]	"Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue." Wang Y., Friedl W., Lamberti C., Ruelfs C., Kruse R., Propping P. Hum. Genet. 100:362-364(1997) [PubMed: 9272156] [Abstract] Cited for: VARIANT HNPCC2 PRO-329.
[33]	"Mutational analysis of the hMLH1 gene using an automated two-dimensional DNA typing system." Sasaki S., Tokino T., Miyatsu T., Muto T., Nakamura Y. Hum. Mutat. 9:164-171(1997) [PubMed: 9067757] [Abstract] Cited for: VARIANT HNPCC2 ARG-67, VARIANT VAL-219.
[34]	"Molecular basis of HNPCC: mutations of MMR genes." Papadopoulos N., Lindblom A. Hum. Mutat. 10:89-99(1997) [PubMed: 9259192] [Abstract] Cited for: REVIEW ON VARIANTS.
[35]	"Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes." Wehner M., Buschhausen L., Lamberti C., Kruse R., Caspari R., Propping P., Friedl W. Hum. Mutat. 10:241-244(1997) [PubMed: 9298827] [Abstract] Cited for: VARIANT HNPCC2 LEU-28.
[36]	"Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families." Wang Q., Desseigne F., Lasset C., Saurin J.-C., Navarro C., Yagci T., Keser I., Bagci H., Luleci G., Gelen T., Chayvialle J.-A., Puisieux A., Ozturk M. Int. J. Cancer 73:831-836(1997) [PubMed: 9399661] [Abstract] Cited for: VARIANTS HNPCC2 GLY-182; THR-295 AND THR-551.
[37]	"Germline HNPCC gene variants have little influence on the risk for sporadic colorectal cancer." Tomlinson I.P.M., Beck N.E., Homfray T., Harocopos C.J., Bodmer W.F. J. Med. Genet. 34:39-42(1997) [PubMed: 9032648] [Abstract] Cited for: VARIANT CRC TYR-77, VARIANT VAL-219.
[38]	"A human compound heterozygote for two MLH1 missense mutations." Hackman P., Tannergaerd P., Osei-Mensa S., Chen J., Kane M.F., Kolodner R.D., Lambert B., Hellgren D., Lindblom A. Nat. Genet. 17:135-136(1997) [PubMed: 9326924] [Abstract] Cited for: VARIANTS HNPCC2 PHE-44 AND THR-441.
[39]	"Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls." Farrington S.M., Lin-Goerke J., Ling J., Wang Y., Burczak J.D., Robbins D.J., Dunlop M.G. Am. J. Hum. Genet. 63:749-759(1998) [PubMed: 9718327] [Abstract] Cited for: VARIANTS HNPCC2, VARIANTS.
[40]	"DGGE screening of mutations in mismatch repair genes (hMSH2 and hMLH1) in 34 Swedish families with colorectal cancer." Liu T., Wahlberg S., Rubio C., Holmberg E., Groenberg H., Lindblom A. Clin. Genet. 53:131-135(1998) [PubMed: 9611074] [Abstract] Cited for: VARIANT CRC GLY-268.
[41]	"Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer." Yuan Y., Han H.-J., Zheng S., Park J.-G. Dis. Colon Rectum 41:434-440(1998) [PubMed: 9559627] [Abstract] Cited for: VARIANT HNPCC2 CYS-217.
[42]	"A novel missense mutation in the DNA mismatch repair gene hMLH1 present among East Asians but not among Europeans." Wang Y., Friedl W., Lamberti C., Noethen M.M., Kruse R., Propping P. Hum. Hered. 48:87-91(1998) [PubMed: 9526167] [Abstract] Cited for: VARIANT ASP-384, ASSOCIATION WITH HNPCC.
[43]	"Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability." Herfarth K.K.-F., Ogunbiyi O.A., Moley J.F., Kodner I.J., Wells S.A. Jr., Goodfellow P.J. Hum. Mutat. 12:73-73(1998) [PubMed: 10627141] [Abstract] Cited for: VARIANT HNPCC2 LYS-69.
[44]	"hMLH1 mutations in hereditary nonpolyposis colorectal cancer kindreds." Panariello L., Scarano M.I., de Rosa M., Capasso L., Renda A., Riegler G., Rossi G.B., Salvatore F., Izzo P. Hum. Mutat. 12:216-217(1998) [PubMed: 10660333] [Abstract] Cited for: VARIANTS HNPCC2 ARG-77 AND PRO-193.
[45]	"Hereditary nonpolyposis colorectal cancer: identification of novel germline mutations in two kindreds not fulfilling the Amsterdam criteria." Quaresima B., Grandinetti C., Baudi F., Tassone P., Barbieri V., Conforti S., Avvedimento E.V., Costanzo F., Venuta S. Hum. Mutat. 12:433-433(1998) [PubMed: 10671064] [Abstract] Cited for: VARIANT HNPCC2 GLY-93.
[46]	"Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer." Hutter P., Couturier A., Membrez V., Joris F., Sappino A.-P., Chappuis P.O. Int. J. Cancer 78:680-684(1998) [PubMed: 9833759] [Abstract] Cited for: VARIANTS HNPCC2 ARG-67; ILE-262 DEL; THR-551; PHE-565 AND MET-716, VARIANT VAL-219.
[47]	"Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer." Heinimann K., Scott R.J., Buerstedde J.-M., Weber W., Siebold K., Attenhofer M., Mueller H., Dobbie Z. Cancer 85:2512-2518(1999) [PubMed: 10375096] [Abstract] Cited for: VARIANTS HNPCC2 ARG-67; ARG-117 AND GLU-485, VARIANT VAL-219.
[48]	"Neurofibromatosis and early onset of cancers in hMLH1-deficient children." Wang Q., Lasset C., Desseigne F., Frappaz D., Bergeron C., Navarro C., Ruano E., Puisieux A. Cancer Res. 59:294-297(1999) [PubMed: 9927034] [Abstract] Cited for: VARIANT HNPCC2 TRP-67.
[49]	"Assessment of pathogenicity criteria for constitutional missense mutations of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2." Genuardi M., Carrara S., Anti M., Ponz de Leon M., Viel A. Eur. J. Hum. Genet. 7:778-782(1999) [PubMed: 10573010] [Abstract] Cited for: VARIANTS HIS-265; ALA-326; PRO-385; ASN-406; THR-618 AND MET-716.
[50]	"Microsatellite instability, a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer." Lamberti C., Kruse R., Ruelfs C., Caspari R., Wang Y., Jungck M., Mathiak M., Malayeri H.R.H., Friedl W., Sauerbruch T., Propping P. Gut 44:839-843(1999) [PubMed: 10323887] [Abstract] Cited for: VARIANTS HNPCC2 LEU-28; GLU-84 AND PRO-329.
[51]	"Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer." Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., Navarro C., Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., Puisieux A. Hum. Genet. 105:79-85(1999) [PubMed: 10480359] [Abstract] Cited for: VARIANTS HNPCC2 TRP-67; MET-117; GLY-182 AND LYS-616 DEL, VARIANT HNPCC TRP-755.
[52]	"Missense mutations in hMLH1 associated with colorectal cancer." Liu T., Tannergaerd P., Hackman P., Rubio C., Kressner U., Lindmark G., Hellgren D., Lambert B., Lindblom A. Hum. Genet. 105:437-441(1999) [PubMed: 10598809] [Abstract] Cited for: VARIANT CRC GLY-578, VARIANT HNPCC2 ALA-618.
[53]	"Novel hMLH1 and hMSH2 germline mutations in African Americans with colorectal cancer." Weber T.K., Chin H.-M., Rodriguez-Bigas M., Keitz B., Gilligan R., O'Malley L., Urf E., Diba N., Pazik J., Petrelli N.J. JAMA 281:2316-2320(1999) [PubMed: 10386556] [Abstract] Cited for: VARIANT HNPCC2 PHE-25, VARIANT TYR-718.
[54]	"Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer." Chan T.L., Yuen S.T., Chung L.P., Ho J.W.C., Kwan K.Y.M., Chan A.S.Y., Ho J.C.Y., Leung S.Y., Wyllie A.H. J. Natl. Cancer Inst. 91:1221-1226(1999) [PubMed: 10413423] [Abstract] Cited for: VARIANT HNPCC2 TYR-264.
[55]	"Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds." Nomura S., Sugano K., Kashiwabara H., Taniguchi T., Fukayama N., Fujita S., Akasu T., Moriya Y., Ohhigashi S., Kakizoe T., Sekiya T. Biochem. Biophys. Res. Commun. 271:120-129(2000) [PubMed: 10777691] [Abstract] Cited for: VARIANTS HNPCC2 VAL-111 AND PRO-588, VARIANTS VAL-219 AND ASP-384.
[56]	"Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach." Fidalgo P., Almeida M.R., West S., Gaspar C., Maia L., Wijnen J., Albuquerque C., Curtis A., Cravo M., Fodde R., Leitao C.N., Burn J. Eur. J. Hum. Genet. 8:49-53(2000) [PubMed: 10713887] [Abstract] Cited for: VARIANTS HNPCC2 MET-213; HIS-607; ALA-618 AND LEU-659.
[57]	"Mutational germline analysis of hMSH2 and hMLH1 genes in early onset colorectal cancer patients." Montera M., Resta N., Simone C., Guanti G., Marchese C., Civitelli S., Mancini A., Pozzi S., De Salvo L., Bruzzone D., Donadini A., Romio L., Mareni C. J. Med. Genet. 37:E7-E7(2000) [PubMed: 10882759] [Abstract] Cited for: VARIANT CRC ARG-260, VARIANT HNPCC2 VAL-304.
[58]	Erratum Montera M., Resta N., Simone C., Guanti G., Marchese C., Civitelli S., Mancini A., Pozzi S., De Salvo L., Bruzzone D., Donadini A., Romio L., Mareni C. J. Med. Genet. 40:472-472(2003)
[59]	"hMLH1 and hMSH2 mutations in families with familial clustering of gastric cancer and hereditary non-polyposis colorectal cancer." Kim J.C., Kim H.C., Roh S.A., Koo K.H., Lee D.H., Yu C.S., Lee J.H., Kim T.W., Lee H.I., Beck N.E., Bodmer W.F. Cancer Detect. Prev. 25:503-510(2001) [PubMed: 12132870] [Abstract] Cited for: VARIANTS GASTRIC CANCER ARG-106; GLN-109 AND LYS-635, VARIANTS HNPCC2 GLY-234; ILE-321; HIS-485 AND ALA-631, VARIANT CRC ILE-472.
[60]	"Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in situ of the breast." Stone J.G., Coleman G., Gusterson B., Marossy A., Lakhani S.R., Ward A., Nash A., McKinna A., A'Hern R., Stratton M.R., Houlston R.S. Cancer Lett. 167:171-174(2001) [PubMed: 11369138] [Abstract] Cited for: VARIANT LCIS HIS-607.
[61]	"Extensive somatic microsatellite mutations in normal human tissue." Vilkki S., Tsao J.-L., Loukola A., Poyhonen M., Vierimaa O., Herva R., Aaltonen L.A., Shibata D. Cancer Res. 61:4541-4544(2001) [PubMed: 11389087] [Abstract] Cited for: INVOLVEMENT IN TUMORIGENESIS.
[62]	"Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?" Mueller-Koch Y., Kopp R., Lohse P., Baretton G., Stoetzer A., Aust D., Daum J., Kerker B., Gross M., Dietmeier W., Holinski-Feder E. Eur. J. Med. Res. 6:473-482(2001) [PubMed: 11726306] [Abstract] Cited for: VARIANTS HNPCC2 VAL-80; PRO-329; ARG-603; ALA-618; LEU-648; PRO-662 AND MET-716, VARIANT HNPCC ARG-689.
[63]	"Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae." Ellison A.R., Lofing J., Bitter G.A. Hum. Mol. Genet. 10:1889-1900(2001) [PubMed: 11555625] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS.
[64]	"Optimization of experimental conditions for RNA-based sequencing of MLH1 and MSH2 genes." Jakubowska A., Gorski B., Kurzawski G., Debniak T., Hadaczek P., Cybulski C., Kladny J., Oszurek O., Scott R.J., Lubinski J. Hum. Mutat. 17:52-60(2001) [PubMed: 11139242] [Abstract] Cited for: VARIANT HNPCC2 ARG-751.
[65]	"Eight novel germline MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer families from Spain." Godino J., de La Hoya M., Diaz-Rubio E., Benito M., Caldes T. Hum. Mutat. 18:549-549(2001) [PubMed: 11748856] [Abstract] Cited for: VARIANTS HNPCC2 HIS-622 AND TRP-687.
[66]	"hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer." Rossi B.M., Lopes A., Oliveira Ferreira F., Nakagawa W.T., Napoli Ferreira C.C., Casali Da Rocha J.C., Simpson C.C., Simpson A.J.G. Ann. Surg. Oncol. 9:555-561(2002) [PubMed: 12095971] [Abstract] Cited for: VARIANTS HNPCC2 SER-338; ARG-603; THR-618 AND TYR-718.
[67]	"Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach." Gille J.J.P., Hogervorst F.B.L., Pals G., Wijnen J.T., van Schooten R.J., Dommering C.J., Meijer G.A., Craanen M.E., Nederlof P.M., de Jong D., McElgunn C.J., Schouten J.P., Menko F.H. Br. J. Cancer 87:892-897(2002) [PubMed: 12373605] [Abstract] Cited for: VARIANTS HNPCC2 ASN-35; HIS-38; MET-117 AND ALA-618.
[68]	"Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma." Baldinu P., Cossu A., Manca A., Satta M.P., Pisano M., Casula M., Dessole S., Pintus A., Tanda F., Palmieri G. Cancer 94:3157-3168(2002) [PubMed: 12115348] [Abstract] Cited for: VARIANT ENDOMETRIAL CANCER VAL-655, VARIANT VAL-219.
[69]	"Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system." Trojan J., Zeuzem S., Randolph A., Hemmerle C., Brieger A., Raedle J., Plotz G., Jiricny J., Marra G. Gastroenterology 122:211-219(2002) [PubMed: 11781295] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HNPCC2 MET-117; GLY-185; CYS-217; ASP-244 AND ALA-326, CHARACTERIZATION OF VARIANTS VAL-219 AND HIS-265.
[70]	"Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing." Cravo M., Afonso A.J., Lage P., Albuquerque C., Maia L., Lacerda C., Fidalgo P., Chaves P., Cruz C., Nobre-Leitao C. Gut 50:405-412(2002) [PubMed: 11839723] [Abstract] Cited for: VARIANTS HNPCC2 CYS-385; HIS-607; THR-618 AND SER-648, VARIANT MET-213.
[71]	"Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer." Nystroem-Lahti M., Perrera C., Raeschle M., Panyushkina-Seiler E., Marra G., Curci A., Quaresima B., Costanzo F., D'Urso M., Venuta S., Jiricny J. Genes Chromosomes Cancer 33:160-167(2002) [PubMed: 11793442] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HNPCC2 ARG-77; GLY-93; ARG-107 AND PRO-659.
[72]	"Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis colorectal cancer." Krueger S., Plaschke J., Pistorius S., Jeske B., Haas S., Kraemer H., Hinterseher I., Bier A., Kreuz F.R., Theissig F., Saeger H.D., Schackert H.K. Hum. Mutat. 19:82-82(2002) [PubMed: 11754112] [Abstract] Cited for: VARIANT HNPCC2 PRO-662, VARIANT VAL-219.
[73]	"Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer." Ward R., Meldrum C., Williams R., Mokany E., Scott R., Turner J., Hawkins N., Burgess B., Groombridge C., Spigelman A. J. Cancer Res. Clin. Oncol. 128:403-411(2002) [PubMed: 12200596] [Abstract] Cited for: VARIANTS HNPCC2 MET-117 AND PRO-247, VARIANTS VAL-219; ALA-618 AND MET-716.
[74]	"Mutations of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with microsatellite instability and abnormalities of mismatch repair protein expression." Scartozzi M., Bianchi F., Rosati S., Galizia E., Antolini A., Loretelli C., Piga A., Bearzi I., Cellerino R., Porfiri E. J. Clin. Oncol. 20:1203-1208(2002) [PubMed: 11870161] [Abstract] Cited for: VARIANT HNPCC2 CYS-646, VARIANT ALA-618.
[75]	"Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States." Kurzawski G., Suchy J., Kladny J., Safranow K., Jakubowska A., Elsakov P., Kucinskas V., Gardovski J., Irmejs A., Sibul H., Huzarski T., Byrski T., Debniak T., Cybulski C., Gronwald J., Oszurek O., Clark J., Gozdz S. , Niepsuj S., Slomski R., Plawski A., Lacka-Wojciechowska A., Rozmiarek A., Fiszer-Maliszewska L., Bebenek M., Sorokin D., Stawicka M., Godlewski D., Richter P., Brozek I., Wysocka B., Jawien A., Banaszkiewicz Z., Kowalczyk J., Czudowska D., Goretzki P.E., Moeslein G., Lubinski J. J. Med. Genet. 39:E65-E65(2002) [PubMed: 12362047] [Abstract] Cited for: VARIANTS HNPCC2 PHE-19; LEU-28; MET-117; PRO-292; THR-681 AND TRP-687, VARIANT VAL-219.
[76]	"Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene." Wagner A., Barrows A., Wijnen J.T., van der Klift H., Franken P.F., Verkuijlen P., Nakagawa H., Geugien M., Jaghmohan-Changur S., Breukel C., Meijers-Heijboer H., Morreau H., van Puijenbroek M., Burn J., Coronel S., Kinarski Y., Okimoto R., Watson P. , Lynch J.F., de la Chapelle A., Lynch H.T., Fodde R. Am. J. Hum. Genet. 72:1088-1100(2003) [PubMed: 12658575] [Abstract] Cited for: VARIANTS HNPCC2 SER-29; ARG-67; LEU-185 AND ASP-244.
[77]	"Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases." Colombino M., Cossu A., Arba A., Manca A., Curci A., Avallone A., Comella G., Botti G., Scintu F., Amoruso M., D'Abbicco D., d'Agnessa M.R., Spanu A., Tanda F., Palmieri G. Ann. Oncol. 14:1530-1536(2003) [PubMed: 14504054] [Abstract] Cited for: VARIANTS COLORECTAL CANCER 325-ARG--GLN-327 DEL; ARG-618 AND PRO-749.
[78]	"Identification of six novel MSH2 and MLH1 germline mutations in HNPCC." Kruger S., Plaschke J., Jeske B., Gorgens H., Pistorius S.R., Bier A., Kreuz F.R., Theissig F., Aust D.E., Saeger H.D., Schackert H.K. Hum. Mutat. 21:445-446(2003) [PubMed: 12655562] [Abstract] Cited for: VARIANT HNPCC2 PRO-586.
[79]	"Genetic analysis of familial colorectal cancer in Israeli Arabs." Chen-Shtoyerman R., Theodor L., Harmati E., Friedman E., Dacka S., Kopelman Y., Sternberg A., Zarivach R., Bar-Meir S., Fireman Z. Hum. Mutat. 21:446-447(2003) [PubMed: 12655564] [Abstract] Cited for: VARIANT CRC GLY-601.
[80]	"Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA." Taylor C.F., Charlton R.S., Burn J., Sheridan E., Taylor G.R. Hum. Mutat. 22:428-433(2003) [PubMed: 14635101] [Abstract] Cited for: VARIANTS HNPCC2 CYS-18; ASP-101; LYS-182; CYS-379; ARG-559 AND LYS-616 DEL.
[81]	"HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1." Raevaara T.E., Gerdes A.-M., Loennqvist K.E., Tybjaerg-Hansen A., Abdel-Rahman W.M., Kariola R., Peltomaeki P., Nystroem-Lahti M. Genes Chromosomes Cancer 40:261-265(2004) [PubMed: 15139004] [Abstract] Cited for: VARIANT HNPCC2 SER-648.
[82]	"Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families." Shin Y.-K., Heo S.-C., Shin J.-H., Hong S.-H., Ku J.-L., Yoo B.-C., Kim I.-J., Park J.-G. Hum. Mutat. 24:351-351(2004) [PubMed: 15365995] [Abstract] Cited for: VARIANTS HNPCC2 CYS-217; GLY-282; LEU-542; PRO-542; PRO-549; PRO-574; PRO-636; SER-640 AND MET-724.
[83]	Erratum Shin Y.K., Heo S.C., Shin J.H., Hong S.H., Ku J.L., Yoo B.C., Kim I.J., Park J.G. Hum. Mutat. 25:224-224(2005)
[84]	"Ten novel MSH2 and MLH1 germline mutations in families with HNPCC." Krueger S., Bier A., Plaschke J., Hoehl R., Aust D.E., Kreuz F.R., Pistorius S.R., Saeger H.D., Rothhammer V., Al-Taie O., Schackert H.K. Hum. Mutat. 24:351-352(2004) [PubMed: 15365996] [Abstract] Cited for: VARIANTS HNPCC2 GLY-41 AND ASN-VAL-PHE-HIS-ILE-719 INS.
[85]	"Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden." Cederquist K., Emanuelsson M., Goeransson I., Holinski-Feder E., Mueller-Koch Y., Golovleva I., Groenberg H. Int. J. Cancer 109:370-376(2004) [PubMed: 14961575] [Abstract] Cited for: VARIANTS HNPCC2 VAL-21; ARG-67; ASN-68 AND LYS-616 DEL.
[86]	Erratum Cederquist K., Emanuelsson M., Goransson I., Holinski-Feder E., Muller-Koch Y., Golovleva I., Gronberg H. Int. J. Cancer 115:1011-1011(2005)
[87]	"Germline epimutation of MLH1 in individuals with multiple cancers." Suter C.M., Martin D.I.K., Ward R.L. Nat. Genet. 36:497-501(2004) [PubMed: 15064764] [Abstract] Cited for: INVOLVEMENT IN HNPCC2 BY EPIGENETIC INHERITANCE.
[88]	"The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer." Lipkin S.M., Rozek L.S., Rennert G., Yang W., Chen P.-C., Hacia J., Hunt N., Shin B., Fodor S., Kokoris M., Greenson J.K., Fearon E., Lynch H., Collins F., Gruber S.B. Nat. Genet. 36:694-699(2004) [PubMed: 15184898] [Abstract] Cited for: VARIANT CRC HIS-132.
[89]	"Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1." Raevaara T.E., Korhonen M.K., Lohi H., Hampel H., Lynch E., Loennqvist K.E., Holinski-Feder E., Sutter C., McKinnon W., Duraisamy S., Gerdes A.-M., Peltomaeki P., Kohonen-Corish M., Mangold E., Macrae F., Greenblatt M., de la Chapelle A., Nystroem M. Gastroenterology 129:537-549(2005) [PubMed: 16083711] [Abstract] Cited for: VARIANTS HNPCC2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; LEU-648; SER-648; LEU-654 AND PRO-659, VARIANTS SER-29; GLY-93; MET-213; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716, CHARACTERIZATION OF VARIANTS HNPCC2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; THR-618; LEU-648; SER-648; LEU-654 AND PRO-659, CHARACTERIZATION OF VARIANTS SER-29; GLY-93; MET-213; VAL-219; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716.
[90]	"Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)." Kurzawski G., Suchy J., Lener M., Klujszo-Grabowska E., Kladny J., Safranow K., Jakubowska K., Jakubowska A., Huzarski T., Byrski T., Debniak T., Cybulski C., Gronwald J., Oszurek O., Oszutowska D., Kowalska E., Gozdz S., Niepsuj S. , Slomski R., Plawski A., Lacka-Wojciechowska A., Rozmiarek A., Fiszer-Maliszewska L., Bebenek M., Sorokin D., Sasiadek M.M., Stembalska A., Grzebieniak Z., Kilar E., Stawicka M., Godlewski D., Richter P., Brozek I., Wysocka B., Limon J., Jawien A., Banaszkiewicz Z., Janiszewska H., Kowalczyk J., Czudowska D., Scott R.J., Lubinski J. Clin. Genet. 69:40-47(2006) [PubMed: 16451135] [Abstract] Cited for: VARIANTS HNPCC2 LEU-28; LYS-35; ARG-67; VAL-111; MET-117; PRO-292; THR-441; LYS-618 DEL; PRO-623; ILE-657 DEL; THR-681; TRP-687 AND ARG-751.
[91]	"Biallelic germline mutations of mismatch-repair genes: a possible cause for multiple pediatric malignancies." Rotterdam initiative on gastrointestinal hereditary tumors Poley J.-W., Wagner A., Hoogmans M.M.C.P., Menko F.H., Tops C., Kros J.M., Reddingius R.E., Meijers-Heijboer H., Kuipers E.J., Dinjens W.N.M. Cancer 109:2349-2356(2007) [PubMed: 17440981] [Abstract] Cited for: VARIANT MMRCS ASN-35.
[92]	"Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays." Takahashi M., Shimodaira H., Andreutti-Zaugg C., Iggo R., Kolodner R.D., Ishioka C. Cancer Res. 67:4595-4604(2007) [PubMed: 17510385] [Abstract] Cited for: VARIANTS HNPCC2 LYS-102 AND GLN-474.
[93]	"Inheritance of a cancer-associated MLH1 germ-line epimutation." Hitchins M.P., Wong J.J.L., Suthers G., Suter C.M., Martin D.I.K., Hawkins N.J., Ward R.L. N. Engl. J. Med. 356:697-705(2007) [PubMed: 17301300] [Abstract] Cited for: INVOLVEMENT IN HNPCC2 BY GERMLINE EPIMUTATION.
[94]	"Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer." Barnetson R.A., Cartwright N., van Vliet A., Haq N., Drew K., Farrington S., Williams N., Warner J., Campbell H., Porteous M.E., Dunlop M.G. Hum. Mutat. 29:367-374(2008) [PubMed: 18033691] [Abstract] Cited for: VARIANTS CRC GLU-67 AND THR-681, VARIANTS ALA-22; GLY-93; SER-309; ASN-406; HIS-607; ALA-618; ARG-689; MET-716; TYR-718 AND ARG-751.
[95]	"A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects." Tournier I., Vezain M., Martins A., Charbonnier F., Baert-Desurmont S., Olschwang S., Wang Q., Buisine M.P., Soret J., Tazi J., Frebourg T., Tosi M. Hum. Mutat. 29:1412-1424(2008) [PubMed: 18561205] [Abstract] Cited for: VARIANT HNPCC2 ILE-330 DEL, VARIANTS HIS-41; ARG-67; ARG-77; SER-98; SER-101; ASP-101; LYS-116; MET-117; ASN-126; MET-213; SER-215; SER-216; PHE-260; CYS-265; HIS-265; ASP-320; ALA-326; ILE-330 DEL; TRP-474; GLN-474; ASP-539; PRO-549; THR-551; ARG-585; ARG-603; HIS-607; PRO-619; SER-640; LEU-640; VAL-655; SER-656; ARG-666; THR-681 AND ARG-689.
+	Additional computationally mapped references.

Web resources

Hereditary non-polyposis colorectal cancer db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U07343 mRNA. Translation: AAC50285.1. U07418 mRNA. Translation: AAA17374.1. U40978 , U40960, U40961, U40962, U40963, U40964, U40965, U40966, U40967, U40968, U40969, U40970, U40971, U40972, U40973, U40974, U40975, U40976, U40977 Genomic DNA. Translation: AAA82079.1. U17857 , U17839, U17840, U17841, U17842, U17843, U17844, U17845, U17846, U17847, U17848, U17849, U17851, U17852, U17853, U17854, U17855, U17856 Genomic DNA. Translation: AAA85687.1. AY217549 Genomic DNA. Translation: AAO22994.1. BC006850 mRNA. Translation: AAH06850.1.
IPI	IPI00029754.
PIR	S43085.
RefSeq	NP_000240.1.
UniGene	Hs.195364
3D structure databases
HSSP	HSSP built from PDB template 1BKN based on UniProtKB P23367.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:27601N.
IntAct	P40692. 7 interactions.
STRING	P40692.
PTM databases
PhosphoSite	P40692.
Proteomic databases
PRIDE	P40692.
Genome annotation databases
Ensembl	ENST00000231790; ENSP00000231790; ENSG00000076242; Homo sapiens. [Genome view] ENST00000383761; ENSP00000373270; ENSG00000076242; Homo sapiens. [Genome view] ENST00000396438; ENSP00000379715; ENSG00000076242; Homo sapiens. [Genome view] ENST00000396447; ENSP00000379724; ENSG00000076242; Homo sapiens. [Genome view] ENST00000413212; ENSP00000400844; ENSG00000076242; Homo sapiens. [Genome view] ENST00000413740; ENSP00000416476; ENSG00000076242; Homo sapiens. [Genome view] ENST00000421440; ENSP00000413580; ENSG00000076242; Homo sapiens. [Genome view] ENST00000429117; ENSP00000407019; ENSG00000076242; Homo sapiens. [Genome view] ENST00000432299; ENSP00000416783; ENSG00000076242; Homo sapiens. [Genome view] ENST00000433611; ENSP00000408641; ENSG00000076242; Homo sapiens. [Genome view] ENST00000435176; ENSP00000402564; ENSG00000076242; Homo sapiens. [Genome view] ENST00000436867; ENSP00000405324; ENSG00000076242; Homo sapiens. [Genome view] ENST00000441265; ENSP00000398392; ENSG00000076242; Homo sapiens. [Genome view] ENST00000442249; ENSP00000387511; ENSG00000076242; Homo sapiens. [Genome view] ENST00000447829; ENSP00000399329; ENSG00000076242; Homo sapiens. [Genome view] ENST00000450420; ENSP00000393006; ENSG00000076242; Homo sapiens. [Genome view] ENST00000450496; ENSP00000392444; ENSG00000076242; Homo sapiens. [Genome view] ENST00000454028; ENSP00000392649; ENSG00000076242; Homo sapiens. [Genome view] ENST00000455445; ENSP00000398272; ENSG00000076242; Homo sapiens. [Genome view] ENST00000456676; ENSP00000416687; ENSG00000076242; Homo sapiens. [Genome view] ENST00000457004; ENSP00000407773; ENSG00000076242; Homo sapiens. [Genome view] ENST00000458009; ENSP00000411066; ENSG00000076242; Homo sapiens. [Genome view] ENST00000458205; ENSP00000402667; ENSG00000076242; Homo sapiens. [Genome view]
GeneID	4292.
KEGG	hsa:4292.
UCSC	uc003cgl.1. human.
Organism-specific databases
CTD	4292.
GeneCards	GC03P037009.
H-InvDB	HIX0003168.
HGNC	HGNC:7127. MLH1.
HPA	CAB013294.
MIM	120436. gene. 158320. phenotype. 276300. phenotype. 608089. phenotype. 609310. phenotype.
Orphanet	144. Colon cancer, familial nonpolyposis. 587. Muir-Torre syndrome.
PharmGKB	PA240.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P40692.
HOVERGEN	P40692.
OMA	SIQVVVK.
Gene expression databases
ArrayExpress	P40692.
Bgee	P40692.
CleanEx	HS_MLH1.
Genevestigator	P40692.
GermOnline	ENSG00000076242. Homo sapiens.
Family and domain databases
InterPro	IPR003594. ATP_bd_ATPase. IPR002099. DNA_mismatch_repair. IPR013507. DNA_mismatch_repair_C. IPR014762. DNA_mismatch_repair_CS. IPR011186. DNA_mismatch_repair_MLH1. IPR014763. DNA_mismatch_repair_N. IPR014721. Ribosomal_S5_D2-typ_fold_subgr. [Graphical view]
Gene3D	G3DSA:3.30.565.10. ATP_bd_ATPase. 1 hit. G3DSA:3.30.230.10. Ribosomal_S5_D2-type_fold. 1 hit.
PANTHER	PTHR10073. DNA_mis_repair. 1 hit. PTHR10073:SF11. MLH1. 1 hit.
Pfam	PF01119. DNA_mis_repair. 1 hit. PF02518. HATPase_c. 1 hit. [Graphical view]
SMART	SM00387. HATPase_c. 1 hit. [Graphical view]
TIGRFAMs	TIGR00585. mutl. 1 hit.
PROSITE	PS00058. DNA_MISMATCH_REPAIR_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16893.
PMAP-CutDB	P40692.
SOURCE	Search...

Entry information

Entry name

MLH1_HUMAN

Accession

Primary (citable) accession number: P40692

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	November 3, 2009
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.