Property Summary

NCBI Gene PubMed Count 82
PubMed Score 151.86
PubTator Score 98.79

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (6)

Disease log2 FC p
nephrosclerosis -1.972 1.1e-02
psoriasis 1.200 4.4e-04
osteosarcoma 2.281 1.4e-07
interstitial cystitis -5.000 7.6e-07
gastric carcinoma -1.400 1.3e-02
ovarian cancer 1.600 7.1e-09

Synonym

Accession Q93088 Q9UNI9
Symbols BHMT1
HEL-S-61p

Gene

PANTHER Protein Class (2)

PDB

1LT7   1LT8   4M3P  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

Protein-protein Interaction (3)

Gene RIF (61)

PMID Text
26213999 The faster evolutionary rate of BHMT2 overall suggests that selective constraints were reduced relative to BHMT.
25846410 Multiple SNPs in BHMT and BHMT2 were identified to be associated with the occurrence of infant obstructive heart defects and interaction effects with maternal use of folic acid supplements.
25144858 Study suggests BHMT holds considerable potential as a blood biomarker for acute liver injury.
24895213 Data suggest BHMT is activated by binding of potassium ions; role of potassium ions in BHMT appears to be structural; potassium ions facilitate specific binding of substrate homocysteine (rather than substrate betaine) to active site of the enzyme.
23645037 Women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a Down Syndrome pregnancy.
22339736 Our study suggests that the polymorphism BHMT G742A may modulate the Down syndrome risk in Brazilian mothers.
22339686 Known common single-nucleotide polymorphisms in MTRR and BHMT genes may not be significant risk factors for cororonary artery disease.
22138536 A transcription variant of exon 4 of betaine-homocysteine methyltransferase (BHMT) produces a loss of function of BHMT in human hepatocarcinoma
21630102 The BHMT 742GA or AA genotypes associated with tobacco consumption (P = 0.016) increase the risk for head and neck squamous cell carcinoma.
21565678 This suggests that polymorphism rs3797546 in the BHMT gene may confer genetic risk of NSCL/P in a recessive manner.
21564312 No significant level of association was found with cleft lip with or without cleft palate and BHMT variants.
21349258 Results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.
21093336 Three SNPs (rs41272270, rs16876512, and rs6875201), located 28kb upstream, in the 5'-UTR and in intron 1 of BHMT, respectively, were significantly correlated with both BHMT activity and protein levels.
20737570 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20664391 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20662904 gene-gene interaction analysis revealed significant epistatic interaction of BHMT2 (rs673752), PEMT (rs12325817), and PCYT1A (rs712012) with maternal NCL/P susceptibility.
20634891 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20458436 Observational study of gene-disease association. (HuGE Navigator)
20453000 Observational study of gene-disease association. (HuGE Navigator)
20346360 Observational study of gene-disease association. (HuGE Navigator)
20031554 Observational study of gene-disease association. (HuGE Navigator)
19948975 Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and genetic testing. (HuGE Navigator)
19936946 Observational study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19777601 Observational study of gene-disease association. (HuGE Navigator)
19737740 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
19692168 Observational study of gene-disease association. (HuGE Navigator)
19683694 Observational study of gene-disease association. (HuGE Navigator)
19635752 betaine-homocysteine methyltransferase gene (BHMT) rs3733890 polymorphism was associated with reduced breast cancer-specific mortality (hazard ratio, 0.64; 95% confidence interval, 0.42-0.97)
19625176 Observational study of gene-disease association. (HuGE Navigator)
19493349 Observational study of gene-disease association. (HuGE Navigator)
19336437 Observational study of gene-disease association. (HuGE Navigator)
19170196 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19161160 Observational study of gene-disease association. (HuGE Navigator)
19048631 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
18988749 Observational study of genetic testing. (HuGE Navigator)
18830263 Observational study of gene-disease association. (HuGE Navigator)
18708404 The BHMT 742 A allele was associated with resuced all-cause mortality.
18676680 Observational study of gene-disease association. (HuGE Navigator)
18635682 Observational study of gene-disease association. (HuGE Navigator)
18498552 betaine-homocysteine methyltransferase (BHMT) transgenic mice are resistant to alcohol or high methionine low folate diet -induced hyperhomocysteinemia and liver steatosis
18457970 Common genetic variation in BHMT and BHMT2 and functionally characterized BHMT SNPs.
18427977 Observational study of genetic testing. (HuGE Navigator)
18262489 Experiments using the glutamate-cysteine ligase modifier subunit knockout mice Gclm(-/-), which are severely impaired in glutathione synthesis, show that BHMT activity is reduced about 75% in Gclm(-/-) compared to Gclm(+/+) mice.
18230680 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17993766 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17705221 The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death.
17436311 Observational study of gene-disease association. (HuGE Navigator)
17376725 Observational study of gene-disease association. (HuGE Navigator)
17376725 association between the homozygous mutant form of BHMT (742G-->A) polymorphism and increased risk for placental abruption.
17119116 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17035141 Observational study of gene-disease association. (HuGE Navigator)
16953798 S-adenosylmethionine and methylthioadenosine downregulaate BHMT expression in HepG2 cells.
16816108 Observational study of gene-disease association. (HuGE Navigator)
15122900 Study using intrinsic tryptophan fluorescence properties of BHMT demonstrates clearly that BHMT catalysis follows an ordered bi-bi mechanism and that betaine binding affinity is dependent on formation of the BHMT-homocysteine complex.
12818402 Observational study of gene-disease association. (HuGE Navigator)
12749058 Observational study of gene-disease association. (HuGE Navigator)
12220488 X-ray structures of human BHMT in its oxidized (Zn-free) and reduced (Zn-replete) forms, the latter in complex with the bisubstrate analog, S(delta-carboxybutyl)-L-homocysteine, were determined at resolutions of 2.15 A and 2.05 A
12071701 BHMT is a tetramer and its ability to methylate homocysteine is not affected by S-Adenosylmethionine (SAMe)
11883905 mutagenesis of the zinc-binding motif reveals that Gly 214 is essential

AA Sequence

MPPVGGKKAKKGILERLNAGEIVIGDGGFVFALEKRGYVKAGPWTPEAAVEHPEAVRQLHREFLRAGSNV      1 - 70
MQTFTFYASEDKLENRGNYVLEKISGQEVNEAACDIARQVADEGDALVAGGVSQTPSYLSCKSETEVKKV     71 - 140
FLQQLEVFMKKNVDFLIAEYFEHVEEAVWAVETLIASGKPVAATMCIGPEGDLHGVPPGECAVRLVKAGA    141 - 210
SIIGVNCHFDPTISLKTVKLMKEGLEAARLKAHLMSQPLAYHTPDCNKQGFIDLPEFPFGLEPRVATRWD    211 - 280
IQKYAREAYNLGVRYIGGCCGFEPYHIRAIAEELAPERGFLPPASEKHGSWGSGLDMHTKPWVRARARKE    281 - 350
YWENLRIASGRPYNPSMSKPDGWGVTKGTAELMQQKEATTEQQLKELFEKQKFKSQ                  351 - 406
//

Text Mined References (83)

PMID Year Title
26213999 2015 Evolutionary Analyses and Natural Selection of Betaine-Homocysteine S-Methyltransferase (BHMT) and BHMT2 Genes.
25846410 2015 Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.
25343990 2015 Genome-wide association study of selenium concentrations.
25144858 2014 Betaine homocysteine methyltransferase (BHMT) as a specific and sensitive blood marker for acute liver injury.
24895213 2014 Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase.
24816252 2014 An atlas of genetic influences on human blood metabolites.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23720494 2013 Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
23645037 2013 Betaine-homocysteine methyltransferase 742G>A polymorphism and risk of down syndrome offspring in a Brazilian population.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23378610 2013 Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22339736 2012 BHMT G742A and MTHFD1 G1958A polymorphisms and Down syndrome risk in the Brazilian population.
22339686 2012 Folate gene polymorphisms MTR A2756G, MTRR A66G, and BHMT G742A and risk for coronary artery disease: a meta-analysis.
22138536 2012 A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma.
21630102 2012 MTHFD1 G1958A, BHMT G742A, TC2 C776G and TC2 A67G polymorphisms and head and neck squamous cell carcinoma risk.
21565678 2011 BHMT gene polymorphisms as risk factors for cleft lip and cleft palate in a Chinese population.
21564312 2011 New evidence for the role of cystathionine beta-synthase in non-syndromic cleft lip with or without cleft palate.
21349258 2011 Folate and choline metabolism gene variants and development of uterine cervical carcinoma.
21093336 2011 Betaine-homocysteine methyltransferase: human liver genotype-phenotype correlation.
21082674 2010 Comprehensive analysis of low-abundance proteins in human urinary exosomes using peptide ligand library technology, peptide OFFGEL fractionation and nanoHPLC-chip-MS/MS.
20737570 2010 Genetic variants in one-carbon metabolism-related genes contribute to NSCLC prognosis in a Chinese population.
20664391 2010 Maternal folate-related gene environment interactions and congenital heart defects.
20662904 2010 Polymorphisms located in the region containing BHMT and BHMT2 genes as maternal protective factors for orofacial clefts.
20634891 2010 Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20458436 2010 Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism.
20453000 2010 A Large-scale genetic association study of esophageal adenocarcinoma risk.
20346360 2010 Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease.
20031554 2008 Variants of folate metabolism genes and the risk of conotruncal cardiac defects.
19948975 2009 Integrative predictive model of coronary artery calcification in atherosclerosis.
19936946 2010 Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19777601 2010 Variants of folate metabolism genes and risk of left-sided cardiac defects.
19737740 2010 Associations of folate and choline metabolism gene polymorphisms with orofacial clefts.
19692168 2010 Genetic susceptibility to distinct bladder cancer subphenotypes.
19683694 2009 Genetic association study of putative functional single nucleotide polymorphisms of genes in folate metabolism and spina bifida.
19635752 2009 High intakes of choline and betaine reduce breast cancer mortality in a population-based study.
19625176 2009 PTEN identified as important risk factor of chronic obstructive pulmonary disease.
19493349 2009 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.
19336437 2009 Vasculopathic and thrombophilic risk factors for spontaneous preterm birth.
19170196 2009 Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.
19161160 2009 An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1).
19048631 2009 Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study.
18988749 2009 MALDI-TOF MS genotyping of polymorphisms related to 1-carbon metabolism using common and mass-modified terminators.
18830263 2009 Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma.
18708404 2008 B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.
18676680 2008 Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.
18635682 2008 Genetic analysis of 56 polymorphisms in 17 genes involved in methionine metabolism in patients with abdominal aortic aneurysm.
18498552 2008 Effect of transgenic extrahepatic expression of betaine-homocysteine methyltransferase on alcohol or homocysteine-induced fatty liver.
18457970 2008 Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization.
18427977 2008 High-throughput multiplex single-nucleotide polymorphism (SNP) analysis in genes involved in methionine metabolism.
18262489 2008 Liver betaine-homocysteine S-methyltransferase activity undergoes a redox switch at the active site zinc.
18230680 2008 Choline metabolism and risk of breast cancer in a population-based study.
18230605 2008 Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17993766 2007 Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?
17705221 2007 Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes.
17436311 2007 Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism.
17376725 2007 Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption.
17119116 2007 Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study.
17035141 2006 Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
16953798 2007 Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine.
16816108 2006 Common genetic polymorphisms affect the human requirement for the nutrient choline.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15122900 2004 Dissecting the catalytic mechanism of betaine-homocysteine S-methyltransferase by use of intrinsic tryptophan fluorescence and site-directed mutagenesis.
12818402 2003 Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease.
12749058 2003 Common variant in betaine-homocysteine methyltransferase (BHMT) and risk for spina bifida.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12475213 2002 S-methylated cysteines in human lens gamma S-crystallins.
12220488 2002 Betaine-homocysteine methyltransferase: zinc in a distorted barrel.
12071701 2002 Expression of recombinant human betaine: homocysteine S-methyltransferase for x-ray crystallographic studies and further characterization of interaction with S-adenosylmethionine.
11516176 2001 Immunohistochemical detection of betaine-homocysteine S-methyltransferase in human, pig, and rat liver and kidney.
11223523 2001 Crystallization and preliminary X-ray crystallographic studies of recombinant human betaine-homocysteine S-methyltransferase.
10529246 1999 Recombinant human liver betaine-homocysteine S-methyltransferase: identification of three cysteine residues critical for zinc binding.
10075673 1999 Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene.
9681996 1998 Human betaine-homocysteine methyltransferase is a zinc metalloenzyme.
9281325 1997 Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8798461 1996 Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase.
1657504 1991 Betaine-homocysteine methyltransferase: organ distribution in man, pig and rat and subcellular distribution in the rat.