HOMOCYSTEINE METABOLIC PATHWAY (PW:0000398)
Description
Homocysteine (Hcy) metabolism is at the cross-roads of several pathways; Hcy itself is a byproduct in the de novo pathway of methionine metabolic cycle. The first reaction of the methionine cycle produces S-adenosylmethionine, also known as AdoMet or SAM, which is the major methyl donor for nucleic acids, proteins, lipids and small molecules. The methyltransfer reaction, carried by a large number of methyltransferases (MTs) generates S-adenosylhomocysteine (SAH), the precursor of Hcy and also a potent inhibitor of MTs. SAH is reversibly hydrolyzed to homocysteine (Hcy) and adenosine by Ahcy. Under equilibrium conditions the production of SAH is favored; however, rapid removal of Hcy and adenosine products, prompts the reaction towards Hcy. Hcy can be methylated to methionine via the cobalamine-dependent and -independent pathways. The first is the predominant reaction in most tissues and is carried out by methionine synthase (Mtr). In the course of the reaction, the cobalamin (Cbl) co-factor can get oxidized rendering the enzyme inactive; reductive methylation carried out by Mtrr restores the functional enzyme (Mtr). The requirement for the 1 carbon (1C) donor 5-methyl tetrahydrofolate and the generation of tetrahydrofolate (THF) in the reaction, engages folate metabolism whose components are the folate cycle and the folate mediated one-carbon metabolic pathways. The cobalamin-independent, betaine-dependent pathway is the major route of Hcy remethylation in the liver. The choline derived betaine is the methyl donor in the reaction catalyzed by the zinc metalloprotein Bhmt with dimethylglycine (DMG) as a by-product. DMG exerts strong feedback inhibition upon Bhmt activity. DMG and sarcosine, the monomethyl glycine derived from the AdoMet-dependent reaction catalyzed by Gnmt, are 1C donors for the production of active folates in mitochondria. Interestingly, Gnmt can interact with 4S polycyclic aromatic hydrocarbons (PAH) which are potential carcinogens; the possible role of Gnmt in cellular detoxification and thus the presence of a second and distinct function, renders it a candidate moonlight protein. The other route of Hcy metabolism is the transsulfuration pathway which results in the production of cysteine and other metabolites downstream of it. AdoMet inhibits the folate-dependent Hcy methylation and activates the first enzyme in the transsulfuration pathway. This way, Hcy metabolism is channeled to remethylation when methionine/AdoMet levels are low, whereas when methionine/AdoMet levels are high, it is channeled to transsulfuration. The remethylation pathways converge on the methionine cycle and lead to homocysteine production; the transsulfuration pathway irreversibly degrades Hcy. The diagram presents an overview of Hcy metabolism. The transsulfuration pathway is presented separately. The pathways of methionine, homocysteine and folate metabolism are intimately interconnected. Defects in enzymes within these pathways have been associated with several disorders and conditions.
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Pathway Diagram:
Genes in Pathway:
G
Ahcy
adenosylhomocysteinase
TAS ISO
RGD
PMID:11741948 PMID:20814827 RGD:730275 , RGD:7242426
NCBI chr 3:164,029,338...164,044,562
G
As3mt
arsenite methyltransferase
TAS
RGD
PMID:11790780 RGD:625365
NCBI chr 1:255,536,879...255,569,245
G
Asmt
acetylserotonin O-methyltransferase
NAS
RGD
PMID:12198599 RGD:1359073
NCBI chr12:21,418,477...21,423,336
G
Carm1
coactivator-associated arginine methyltransferase 1
ISO
RGD
PMID:15866169 RGD:1359044
NCBI chr 8:28,373,370...28,418,056
G
Comt
catechol-O-methyltransferase
TAS
RGD
PMID:12584150 RGD:1359089
NCBI chr11:96,072,371...96,091,956
G
Dnmt1
DNA methyltransferase 1
TAS
RGD
PMID:12473678 RGD:1359078
NCBI chr 8:27,716,797...27,763,405
G
Dot1l
DOT1 like histone lysine methyltransferase
ISO
RGD
PMID:12628190 RGD:1359080
NCBI chr 7:9,569,439...9,607,095
G
Gamt
guanidinoacetate N-methyltransferase
IDA
RGD
PMID:15533043 RGD:1359081
NCBI chr 7:10,099,267...10,102,083
G
Gnmt
glycine N-methyltransferase
IDA
RGD
PMID:15347642 RGD:1359070
NCBI chr 9:21,752,235...21,756,368
G
Hnmt
histamine N-methyltransferase
ISS
RGD
PMID:11566133 RGD:1359041
NCBI chr 3:26,978,274...27,010,291
G
Icmt
isoprenylcysteine carboxyl methyltransferase
ISS
RGD
PMID:15625008 RGD:1359083
NCBI chr 5:168,084,487...168,097,519
G
Mrm2
mitochondrial rRNA methyltransferase 2
ISO
RGD
PMID:11827451 RGD:1359074
NCBI chr12:19,423,448...19,428,662
G
Mthfr
methylenetetrahydrofolate reductase
ISO
RGD
PMID:20814827 RGD:7242426
NCBI chr 5:163,748,346...163,768,141
G
Nnmt
nicotinamide N-methyltransferase
ISO
RGD
PMID:15922112 RGD:1359084
NCBI chr 8:57,820,156...57,851,301
G
Pcmt1
protein-L-isoaspartate (D-aspartate) O-methyltransferase 1
IDA
RGD
PMID:8263531 RGD:729481
NCBI chr 1:3,932,161...3,980,751
G
Pemt
phosphatidylethanolamine N-methyltransferase
IDA
RGD
PMID:8344945 RGD:729486
NCBI chr10:45,275,434...45,349,651
G
Pnmt
phenylethanolamine-N-methyltransferase
TAS
RGD
PMID:12438084 RGD:1359087
NCBI chr10:83,881,211...83,882,849
G
Prmt1
protein arginine methyltransferase 1
ISS
RGD
PMID:15866169 RGD:1359044
NCBI chr 1:104,595,339...104,605,552
G
Prmt3
protein arginine methyltransferase 3
ISS
RGD
PMID:15866169 RGD:1359044
NCBI chr 1:108,628,899...108,718,803
G
Prmt5
protein arginine methyltransferase 5
ISO
RGD
PMID:15866169 RGD:1359044
NCBI chr15:31,938,927...31,948,318
G
Prmt6
protein arginine methyltransferase 6
ISO
RGD
PMID:15866169 RGD:1359044
NCBI chr 2:200,615,780...200,620,790
G
Rnmt
RNA (guanine-7-) methyltransferase
ISO
RGD
PMID:11472630 RGD:1359071
NCBI chr18:64,156,067...64,179,601
G
Setdb1
SET domain bifurcated histone lysine methyltransferase 1
ISO
RGD
PMID:11959841 RGD:1359072
NCBI chr 2:185,587,722...185,619,084
G
Suv39h2
SUV39H2 histone lysine methyltransferase
ISO
RGD
PMID:11094092 RGD:1359810
NCBI chr17:79,665,467...79,684,492
G
Trdmt1
tRNA aspartic acid methyltransferase 1
ISO
RGD
PMID:12794065 RGD:1359088
NCBI chr17:81,510,740...81,554,036
G
Mthfr
methylenetetrahydrofolate reductase
ISO
RGD
PMID:20814827 RGD:7242426
NCBI chr 5:163,748,346...163,768,141
G
Mtr
5-methyltetrahydrofolate-homocysteine methyltransferase
IDA ISO
RGD
PMID:15845641 PMID:20814827 RGD:1359026 , RGD:7242426
NCBI chr17:62,911,705...62,996,544
G
Mtrr
5-methyltetrahydrofolate-homocysteine methyltransferase reductase
ISO
RGD
PMID:15979034 PMID:20814827 RGD:1359037 , RGD:7242426
NCBI chr 1:36,695,376...36,727,341
G
Ahcy
adenosylhomocysteinase
ISO
SMPDB SMP:00123
NCBI chr 3:164,029,338...164,044,562
G
Aldh7a1
aldehyde dehydrogenase 7 family, member A1
ISO
SMPDB SMP:00123
NCBI chr18:52,208,035...52,240,293
G
Bhmt
betaine-homocysteine S-methyltransferase
IDA ISO
SMPDB PMID:15845641 PMID:20814827 PMID:20346934 SMP:00123, RGD:1359026 , RGD:7242426 , RGD:7242428
NCBI chr 2:26,594,852...26,614,429
G
Chdh
choline dehydrogenase
ISO
SMPDB SMP:00123
NCBI chr16:5,199,738...5,232,067
G
Mat2a
methionine adenosyltransferase 2A
ISO
SMPDB SMP:00123
NCBI chr 4:106,048,043...106,053,612
G
Mat2b
methionine adenosyltransferase 2 non-catalytic beta subunit
ISO
SMPDB SMP:00123
NCBI chr10:25,609,202...25,626,694
G
Mtr
5-methyltetrahydrofolate-homocysteine methyltransferase
ISO
SMPDB SMP:00123
NCBI chr17:62,911,705...62,996,544
G
Pemt
phosphatidylethanolamine N-methyltransferase
ISO
SMPDB SMP:00123
NCBI chr10:45,275,434...45,349,651
G
Cbs
cystathionine beta synthase
ISO
SMPDB PMID:20162368 SMP:00455, RGD:7242427
NCBI chr20:9,709,394...9,733,925
G
Cdo1
cysteine dioxygenase type 1
ISO
RGD
PMID:20162368 RGD:7242427
NCBI chr18:41,619,076...41,633,719
G
Csad
cysteine sulfinic acid decarboxylase
ISO
RGD
PMID:20162368 RGD:7242427
NCBI chr 7:135,187,175...135,216,495
G
Cth
cystathionine gamma-lyase
ISO
SMPDB PMID:20162368 SMP:00455, RGD:7242427
NCBI chr 2:249,634,731...249,661,066
Pathway Gene Annotations
Disease Annotations Associated with Genes in the homocysteine metabolic pathway
Ahcy abdominal aortic aneurysm , amino acid metabolic disorder , Animal Disease Models , Experimental Arthritis , genetic disease , hyperhomocysteinemia , hypermethioninemia , hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase , hypertension , Hypoxia , lung adenocarcinoma , metabolic dysfunction-associated steatotic liver disease , pyridoxine deficiency anemia , Rhabdomyolysis , Wilson disease As3mt Arsenic Poisoning , attention deficit hyperactivity disorder , Birth Weight , Developmental Disabilities , Glandular and Epithelial Neoplasms , Insulin Resistance , Lung Neoplasms , Micronuclei, Chromosome-Defective , schizophrenia , urinary bladder cancer Asmt autistic disorder , Wilson disease Carm1 asthma , estrogen-receptor positive breast cancer , hepatocellular adenoma , hepatocellular carcinoma , Neurodevelopmental Disorders , prostate carcinoma in situ , Prostatic Neoplasms , psoriasis Comt Acute Pain , alcohol dependence , alcohol use disorder , amphetamine abuse , Animal Mammary Neoplasms , attention deficit hyperactivity disorder , autism spectrum disorder , autistic disorder , Bardet-Biedl syndrome , bipolar disorder , Brain Injuries , breast cancer , Breast Neoplasms , bulimia nervosa , cannabis abuse , cannabis dependence , Catalepsy , Chemical and Drug Induced Liver Injury , Child Behavior Disorders , cocaine dependence , Cocaine-Related Disorders , cognitive disorder , DiGeorge syndrome , dilated cardiomyopathy , disease of mental health , drug dependence , Drug-Induced Dyskinesia , endometrial cancer , epilepsy , eumycotic mycetoma , Experimental Autoimmune Encephalomyelitis , Experimental Diabetes Mellitus , Fatigue , Fetal Growth Retardation , fibromyalgia , hepatocellular carcinoma , heroin dependence , Hyperalgesia , hypertension , intermittent explosive disorder , leiomyoma , lung cancer , Lymphatic Metastasis , Memory Disorders , morphine dependence , Musculoskeletal Pain , Neck Pain , neonatal abstinence syndrome , nicotine dependence , obesity , obsessive-compulsive disorder , opiate dependence , ovarian cancer , Pain , panic disorder , Paranoid Disorders , Parkinsonism , pathological gambling , pheochromocytoma , polycystic ovary syndrome , pre-eclampsia , prostate cancer , Prostatic Neoplasms , psoriasis , Recurrence , renal cell carcinoma , schizophrenia , Schizophrenia Spectrum and Other Psychotic Disorders , Temporomandibular Joint Disorders , uremia , urinary bladder cancer , velocardiofacial syndrome , Venous Thrombosis , vitiligo , withdrawal disorder Dnmt1 acute myeloid leukemia , adenocarcinoma , alopecia areata , anxiety disorder , asthma , Ataxia , autism spectrum disorder , autoimmune disease , autosomal dominant cerebellar ataxia, deafness and narcolepsy , Beckwith-Wiedemann syndrome , Binge Drinking , Brain Injuries , Breast Neoplasms , bronchiolo-alveolar adenocarcinoma , Carcinogenesis , carcinoma , cardiomyopathy , cerebellar ataxia , Charcot-Marie-Tooth disease , choline deficiency disease , chronic myeloid leukemia , clear cell renal cell carcinoma , Colonic Neoplasms , Colorectal Neoplasms , congenital heart disease , congestive heart failure , dementia , Endometrial Neoplasms , Endometrioid Carcinomas , endometriosis , endometriosis of uterus , Experimental Arthritis , fetal alcohol spectrum disorder , Fetal Growth Retardation , genetic disease , Graves' disease , Hearing Loss , hepatocellular carcinoma , hereditary sensory neuropathy , hereditary sensory neuropathy type 1E , hypertrophic cardiomyopathy , liver cirrhosis , lung cancer , lung carcinoma , lung non-small cell carcinoma , medulloblastoma , metabolic dysfunction and alcohol associated liver disease , middle cerebral artery infarction , mucoepidermoid carcinoma , myelodysplastic syndrome , Neoplasm Invasiveness , Oral Lichen Planus , Ovarian Neoplasms , pancreatic ductal carcinoma , Pancreatic Intraepithelial Neoplasia , Peritoneal Fibrosis , Pituitary Stalk Interruption Syndrome , prostate adenocarcinoma , prostate cancer , prostate carcinoma in situ , Prostatic Neoplasms , rheumatoid arthritis , schizophrenia , spastic ataxia , Spastic Paraparesis , Stomach Neoplasms , systemic lupus erythematosus , type 2 diabetes mellitus , urinary bladder cancer , Uterine Cervical Neoplasms Dot1l acute biphenotypic leukemia , Colorectal Neoplasms , Developmental Disease , dilated cardiomyopathy 1A , genetic disease , lung adenocarcinoma , Nil-Deshwan neurodevelopmental syndrome , Prostatic Neoplasms Gamt amino acid metabolic disorder , cerebral creatine deficiency syndrome , epilepsy , genetic disease , guanidinoacetate methyltransferase deficiency , intellectual disability , late onset Parkinson's disease , Nervous System Malformations , pre-eclampsia , transient cerebral ischemia Gnmt Chronic Hepatitis , glycine N-methyltransferase deficiency , hepatitis , hepatocellular carcinoma , hyperhomocysteinemia , hypermethioninemia , Liver Neoplasms , metabolic dysfunction-associated steatotic liver disease , Prostatic Neoplasms Hnmt asthma , atopic dermatitis , autistic disorder , autosomal recessive intellectual developmental disorder 51 , brain infarction , Bronchial Hyperreactivity , Down syndrome , drug allergy , Dyssomnias , essential tremor , gastrointestinal system disease , Huntington's disease , Language Development Disorders , Parkinson's disease , Pick's disease , rhinitis , schizophrenia , ulcerative colitis , urticaria Mrm2 mitochondrial DNA depletion syndrome 17 Mthfr abdominal aortic aneurysm , acute kidney failure , acute lymphoblastic leukemia , acute myeloid leukemia , Albuminuria , alcoholic liver cirrhosis , allergic disease , alopecia , Alzheimer's disease , amyotrophic lateral sclerosis , anemia , angle-closure glaucoma , ankylosing spondylitis , aphthous stomatitis , Arsenic Poisoning , Arterial Occlusive Diseases , asthma , atherosclerosis , attention deficit hyperactivity disorder , autism spectrum disorder , autistic disorder , B-Cell Chronic Lymphocytic Leukemia , Banti's Syndrome , bipolar disorder , brain ischemia , Breast Neoplasms , Budd-Chiari syndrome , cardia cancer , cardiovascular system disease , carotid stenosis , cataract , cerebral infarction , cervical cancer , Chemical and Drug Induced Liver Injury , cholangiocarcinoma , chronic kidney disease , chronic myeloid leukemia , clear cell renal cell carcinoma , cleft lip , clubfoot , coarctation of the aorta , Cognitive Dysfunction , Colonic Neoplasms , Colorectal Neoplasms , congenital heart disease , Conotruncal Cardiac Defects , coronary artery disease , Coronary Disease , coronary restenosis , Crohn's disease , Cytomegalovirus Infections , depressive disorder , Developmental Disabilities , dextro-looped transposition of the great arteries , diabetes mellitus , diabetic angiopathy , Diabetic Nephropathies , diabetic retinopathy , diffuse large B-cell lymphoma , Down syndrome , Drug Eruptions , Drug-Related Side Effects and Adverse Reactions , end stage renal disease , Endometrial Neoplasms , epilepsy with generalized tonic-clonic seizures , Experimental Diabetes Mellitus , eye disease , factor VIII deficiency , familial Mediterranean fever , Female Infertility , Folate-Sensitive Neural Tube Defects , follicular lymphoma , gastrointestinal stromal tumor , gastrointestinal system disease , genetic disease , glomerulonephritis , graft-versus-host disease , Graves' disease , Habitual Abortions , Hearing Loss , Helicobacter Infections , Hematologic Neoplasms , hematopoietic system disease , hepatic veno-occlusive disease , hepatitis B , hepatocellular carcinoma , hyperhomocysteinemia , hyperthyroidism , hypopituitarism , hypothyroidism , inflammatory bowel disease , Inherited Blood Coagulation Disease , intellectual disability , intracranial sinus thrombosis , ischemia , kidney disease , kidney failure , Kuhnt-Junius degeneration , Left Ventricular Hypertrophy , Leukoencephalopathies , leukopenia , liver benign neoplasm , liver cirrhosis , liver disease , Lung Neoplasms , lung small cell carcinoma , lymphoma , male infertility , Malnutrition , Maxillofacial Abnormalities , Meniere's disease , metabolic dysfunction-associated steatotic liver disease , Methylenetetrahydrofolate Reductase Deficiency , Microsatellite Instability , Microvascular Angina , migraine , migraine with aura , mitral valve disease , Mthfr Deficiency, Thermolabile Type , mucositis , multiple myeloma , myeloid neoplasm , myelomeningocele , myocardial infarction , Necrosis , Neoplasm Metastasis , nephroblastoma , nephrosclerosis , nervous system disease , neural tube defect , neutropenia , non-arteritic anterior ischemic optic neuropathy , non-Hodgkin lymphoma , open-angle glaucoma , oral squamous cell carcinoma , osteonecrosis , osteosarcoma , pancreatic cancer , papillomavirus infectious disease , Parkinson's disease , peripheral artery disease , portal vein thrombosis , Prenatal Exposure Delayed Effects , prostate cancer , Prostatic Neoplasms , pulmonary embolism , rectal benign neoplasm , renal artery disease , renal cell carcinoma , retinal disease , retinal vein occlusion , rheumatoid arthritis , schizophrenia , sickle cell anemia , skin disease , smallpox , spina bifida , spinal cord disease , sporadic breast cancer , squamous cell carcinoma , steatotic liver disease , stomach cancer , Stomach Neoplasms , stroke , Sudden Hearing Loss , tetralogy of Fallot , thrombocytopenia , thrombophilia , thrombophilia due to thrombin defect , thrombosis , Thrombotic Microangiopathies , thyrotoxicosis , transitional cell carcinoma , type 1 diabetes mellitus , type 2 diabetes mellitus , urinary bladder cancer , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Vascular Calcification , vascular dementia , vascular disease , Venous Thromboembolism , Venous Thrombosis Nnmt abdominal aortic aneurysm , Arterial Occlusive Diseases , atherosclerosis , basal cell carcinoma , coronary artery disease , hepatocellular carcinoma , left ventricular failure , Metabolic Syndrome , Pulmonary Arterial Hypertension , renal cell carcinoma Pcmt1 Alzheimer's disease , Aortic Injuries , congestive heart failure , high grade glioma , malignant astrocytoma , spina bifida Pemt Experimental Diabetes Mellitus , Experimental Liver Neoplasms , liver cirrhosis , metabolic dysfunction and alcohol associated liver disease , metabolic dysfunction-associated steatotic liver disease Pnmt Alzheimer's disease , Contusions , Experimental Diabetes Mellitus , hypertension , hypoglycemia , multiple sclerosis , Reperfusion Injury Prmt1 asthma , cleft palate , Cocaine-Related Disorders , Diabetic Nephropathies Prmt3 asthma Prmt5 asthma , Cocaine-Related Disorders , diffuse large B-cell lymphoma , idiopathic scoliosis , Leydig cell tumor , medulloblastoma , multiple myeloma , seminoma , Triple Negative Breast Neoplasms Prmt6 cocaine dependence , Cocaine-Related Disorders Setdb1 autistic disorder , high grade glioma , Huntington's disease , lung cancer , malignant mesothelioma , melanoma , prostate cancer , Prostatic Neoplasms , Rett syndrome , schizophrenia Suv39h2 Parakeratosis
abdominal aortic aneurysm Ahcy , Mthfr , Nnmt acute biphenotypic leukemia Dot1l acute kidney failure Mthfr acute lymphoblastic leukemia Mthfr acute myeloid leukemia Dnmt1 , Mthfr Acute Pain Comt adenocarcinoma Dnmt1 Albuminuria Mthfr alcohol dependence Comt alcohol use disorder Comt alcoholic liver cirrhosis Mthfr allergic disease Mthfr alopecia Mthfr alopecia areata Dnmt1 Alzheimer's disease Mthfr , Pcmt1 , Pnmt amino acid metabolic disorder Ahcy , Gamt amphetamine abuse Comt amyotrophic lateral sclerosis Mthfr anemia Mthfr angle-closure glaucoma Mthfr Animal Disease Models Ahcy Animal Mammary Neoplasms Comt ankylosing spondylitis Mthfr anxiety disorder Dnmt1 Aortic Injuries Pcmt1 aphthous stomatitis Mthfr Arsenic Poisoning As3mt , Mthfr Arterial Occlusive Diseases Mthfr , Nnmt asthma Carm1 , Dnmt1 , Hnmt , Mthfr , Prmt1 , Prmt3 , Prmt5 Ataxia Dnmt1 atherosclerosis Mthfr , Nnmt atopic dermatitis Hnmt attention deficit hyperactivity disorder As3mt , Comt , Mthfr autism spectrum disorder Comt , Dnmt1 , Mthfr autistic disorder Asmt , Comt , Hnmt , Mthfr , Setdb1 autoimmune disease Dnmt1 autosomal dominant cerebellar ataxia, deafness and narcolepsy Dnmt1 autosomal recessive intellectual developmental disorder 51 Hnmt B-Cell Chronic Lymphocytic Leukemia Mthfr Banti's Syndrome Mthfr Bardet-Biedl syndrome Comt basal cell carcinoma Nnmt Beckwith-Wiedemann syndrome Dnmt1 Binge Drinking Dnmt1 bipolar disorder Comt , Mthfr Birth Weight As3mt brain infarction Hnmt Brain Injuries Comt , Dnmt1 brain ischemia Mthfr breast cancer Comt Breast Neoplasms Comt , Dnmt1 , Mthfr Bronchial Hyperreactivity Hnmt bronchiolo-alveolar adenocarcinoma Dnmt1 Budd-Chiari syndrome Mthfr bulimia nervosa Comt cannabis abuse Comt cannabis dependence Comt Carcinogenesis Dnmt1 carcinoma Dnmt1 cardia cancer Mthfr cardiomyopathy Dnmt1 cardiovascular system disease Mthfr carotid stenosis Mthfr Catalepsy Comt cataract Mthfr cerebellar ataxia Dnmt1 cerebral creatine deficiency syndrome Gamt cerebral infarction Mthfr cervical cancer Mthfr Charcot-Marie-Tooth disease Dnmt1 Chemical and Drug Induced Liver Injury Comt , Mthfr Child Behavior Disorders Comt cholangiocarcinoma Mthfr choline deficiency disease Dnmt1 Chronic Hepatitis Gnmt chronic kidney disease Mthfr chronic myeloid leukemia Dnmt1 , Mthfr clear cell renal cell carcinoma Dnmt1 , Mthfr cleft lip Mthfr cleft palate Prmt1 clubfoot Mthfr coarctation of the aorta Mthfr cocaine dependence Comt , Prmt6 Cocaine-Related Disorders Comt , Prmt1 , Prmt5 , Prmt6 cognitive disorder Comt Cognitive Dysfunction Mthfr Colonic Neoplasms Dnmt1 , Mthfr Colorectal Neoplasms Dnmt1 , Dot1l , Mthfr congenital heart disease Dnmt1 , Mthfr congestive heart failure Dnmt1 , Pcmt1 Conotruncal Cardiac Defects Mthfr Contusions Pnmt coronary artery disease Mthfr , Nnmt Coronary Disease Mthfr coronary restenosis Mthfr Crohn's disease Mthfr Cytomegalovirus Infections Mthfr dementia Dnmt1 depressive disorder Mthfr Developmental Disabilities As3mt , Mthfr Developmental Disease Dot1l dextro-looped transposition of the great arteries Mthfr diabetes mellitus Mthfr diabetic angiopathy Mthfr Diabetic Nephropathies Mthfr , Prmt1 diabetic retinopathy Mthfr diffuse large B-cell lymphoma Mthfr , Prmt5 DiGeorge syndrome Comt dilated cardiomyopathy Comt dilated cardiomyopathy 1A Dot1l disease of mental health Comt Down syndrome Hnmt , Mthfr drug allergy Hnmt drug dependence Comt Drug Eruptions Mthfr Drug-Induced Dyskinesia Comt Drug-Related Side Effects and Adverse Reactions Mthfr Dyssomnias Hnmt end stage renal disease Mthfr endometrial cancer Comt Endometrial Neoplasms Dnmt1 , Mthfr Endometrioid Carcinomas Dnmt1 endometriosis Dnmt1 endometriosis of uterus Dnmt1 epilepsy Comt , Gamt epilepsy with generalized tonic-clonic seizures Mthfr essential tremor Hnmt estrogen-receptor positive breast cancer Carm1 eumycotic mycetoma Comt Experimental Arthritis Ahcy , Dnmt1 Experimental Autoimmune Encephalomyelitis Comt Experimental Diabetes Mellitus Comt , Mthfr , Pemt , Pnmt Experimental Liver Neoplasms Pemt eye disease Mthfr factor VIII deficiency Mthfr familial Mediterranean fever Mthfr Fatigue Comt Female Infertility Mthfr fetal alcohol spectrum disorder Dnmt1 Fetal Growth Retardation Comt , Dnmt1 fibromyalgia Comt Folate-Sensitive Neural Tube Defects Mthfr follicular lymphoma Mthfr gastrointestinal stromal tumor Mthfr gastrointestinal system disease Hnmt , Mthfr genetic disease Ahcy , Dnmt1 , Dot1l , Gamt , Mthfr Glandular and Epithelial Neoplasms As3mt glomerulonephritis Mthfr glycine N-methyltransferase deficiency Gnmt graft-versus-host disease Mthfr Graves' disease Dnmt1 , Mthfr guanidinoacetate methyltransferase deficiency Gamt Habitual Abortions Mthfr Hearing Loss Dnmt1 , Mthfr Helicobacter Infections Mthfr Hematologic Neoplasms Mthfr hematopoietic system disease Mthfr hepatic veno-occlusive disease Mthfr hepatitis Gnmt hepatitis B Mthfr hepatocellular adenoma Carm1 hepatocellular carcinoma Carm1 , Comt , Dnmt1 , Gnmt , Mthfr , Nnmt hereditary sensory neuropathy Dnmt1 hereditary sensory neuropathy type 1E Dnmt1 heroin dependence Comt high grade glioma Pcmt1 , Setdb1 Huntington's disease Hnmt , Setdb1 Hyperalgesia Comt hyperhomocysteinemia Ahcy , Gnmt , Mthfr hypermethioninemia Ahcy , Gnmt hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase Ahcy hypertension Ahcy , Comt , Pnmt hyperthyroidism Mthfr hypertrophic cardiomyopathy Dnmt1 hypoglycemia Pnmt hypopituitarism Mthfr hypothyroidism Mthfr Hypoxia Ahcy idiopathic scoliosis Prmt5 inflammatory bowel disease Mthfr Inherited Blood Coagulation Disease Mthfr Insulin Resistance As3mt intellectual disability Gamt , Mthfr intermittent explosive disorder Comt intracranial sinus thrombosis Mthfr ischemia Mthfr kidney disease Mthfr kidney failure Mthfr Kuhnt-Junius degeneration Mthfr Language Development Disorders Hnmt late onset Parkinson's disease Gamt left ventricular failure Nnmt Left Ventricular Hypertrophy Mthfr leiomyoma Comt Leukoencephalopathies Mthfr leukopenia Mthfr Leydig cell tumor Prmt5 liver benign neoplasm Mthfr liver cirrhosis Dnmt1 , Mthfr , Pemt liver disease Mthfr Liver Neoplasms Gnmt lung adenocarcinoma Ahcy , Dot1l lung cancer Comt , Dnmt1 , Setdb1 lung carcinoma Dnmt1 Lung Neoplasms As3mt , Mthfr lung non-small cell carcinoma Dnmt1 lung small cell carcinoma Mthfr Lymphatic Metastasis Comt lymphoma Mthfr male infertility Mthfr malignant astrocytoma Pcmt1 malignant mesothelioma Setdb1 Malnutrition Mthfr Maxillofacial Abnormalities Mthfr medulloblastoma Dnmt1 , Prmt5 melanoma Setdb1 Memory Disorders Comt Meniere's disease Mthfr metabolic dysfunction and alcohol associated liver disease Dnmt1 , Pemt metabolic dysfunction-associated steatotic liver disease Ahcy , Gnmt , Mthfr , Pemt Metabolic Syndrome Nnmt Methylenetetrahydrofolate Reductase Deficiency Mthfr Micronuclei, Chromosome-Defective As3mt Microsatellite Instability Mthfr Microvascular Angina Mthfr middle cerebral artery infarction Dnmt1 migraine Mthfr migraine with aura Mthfr mitochondrial DNA depletion syndrome 17 Mrm2 mitral valve disease Mthfr morphine dependence Comt Mthfr Deficiency, Thermolabile Type Mthfr mucoepidermoid carcinoma Dnmt1 mucositis Mthfr multiple myeloma Mthfr , Prmt5 multiple sclerosis Pnmt Musculoskeletal Pain Comt myelodysplastic syndrome Dnmt1 myeloid neoplasm Mthfr myelomeningocele Mthfr myocardial infarction Mthfr Neck Pain Comt Necrosis Mthfr neonatal abstinence syndrome Comt Neoplasm Invasiveness Dnmt1 Neoplasm Metastasis Mthfr nephroblastoma Mthfr nephrosclerosis Mthfr nervous system disease Mthfr Nervous System Malformations Gamt neural tube defect Mthfr Neurodevelopmental Disorders Carm1 neutropenia Mthfr nicotine dependence Comt Nil-Deshwan neurodevelopmental syndrome Dot1l non-arteritic anterior ischemic optic neuropathy Mthfr non-Hodgkin lymphoma Mthfr obesity Comt obsessive-compulsive disorder Comt open-angle glaucoma Mthfr opiate dependence Comt Oral Lichen Planus Dnmt1 oral squamous cell carcinoma Mthfr osteonecrosis Mthfr osteosarcoma Mthfr ovarian cancer Comt Ovarian Neoplasms Dnmt1 Pain Comt pancreatic cancer Mthfr pancreatic ductal carcinoma Dnmt1 Pancreatic Intraepithelial Neoplasia Dnmt1 panic disorder Comt papillomavirus infectious disease Mthfr Parakeratosis Suv39h2 Paranoid Disorders Comt Parkinson's disease Hnmt , Mthfr Parkinsonism Comt pathological gambling Comt peripheral artery disease Mthfr Peritoneal Fibrosis Dnmt1 pheochromocytoma Comt Pick's disease Hnmt Pituitary Stalk Interruption Syndrome Dnmt1 polycystic ovary syndrome Comt portal vein thrombosis Mthfr pre-eclampsia Comt , Gamt Prenatal Exposure Delayed Effects Mthfr prostate adenocarcinoma Dnmt1 prostate cancer Comt , Dnmt1 , Mthfr , Setdb1 prostate carcinoma in situ Carm1 , Dnmt1 Prostatic Neoplasms Carm1 , Comt , Dnmt1 , Dot1l , Gnmt , Mthfr , Setdb1 psoriasis Carm1 , Comt Pulmonary Arterial Hypertension Nnmt pulmonary embolism Mthfr pyridoxine deficiency anemia Ahcy rectal benign neoplasm Mthfr Recurrence Comt renal artery disease Mthfr renal cell carcinoma Comt , Mthfr , Nnmt Reperfusion Injury Pnmt retinal disease Mthfr retinal vein occlusion Mthfr Rett syndrome Setdb1 Rhabdomyolysis Ahcy rheumatoid arthritis Dnmt1 , Mthfr rhinitis Hnmt schizophrenia As3mt , Comt , Dnmt1 , Hnmt , Mthfr , Setdb1 Schizophrenia Spectrum and Other Psychotic Disorders Comt seminoma Prmt5 sickle cell anemia Mthfr skin disease Mthfr smallpox Mthfr spastic ataxia Dnmt1 Spastic Paraparesis Dnmt1 spina bifida Mthfr , Pcmt1 spinal cord disease Mthfr sporadic breast cancer Mthfr squamous cell carcinoma Mthfr steatotic liver disease Mthfr stomach cancer Mthfr Stomach Neoplasms Dnmt1 , Mthfr stroke Mthfr Sudden Hearing Loss Mthfr systemic lupus erythematosus Dnmt1 Temporomandibular Joint Disorders Comt tetralogy of Fallot Mthfr thrombocytopenia Mthfr thrombophilia Mthfr thrombophilia due to thrombin defect Mthfr thrombosis Mthfr Thrombotic Microangiopathies Mthfr thyrotoxicosis Mthfr transient cerebral ischemia Gamt transitional cell carcinoma Mthfr Triple Negative Breast Neoplasms Prmt5 type 1 diabetes mellitus Mthfr type 2 diabetes mellitus Dnmt1 , Mthfr ulcerative colitis Hnmt uremia Comt urinary bladder cancer As3mt , Comt , Dnmt1 , Mthfr urticaria Hnmt Uterine Cervical Dysplasia Mthfr Uterine Cervical Neoplasms Dnmt1 , Mthfr Vascular Calcification Mthfr vascular dementia Mthfr vascular disease Mthfr velocardiofacial syndrome Comt Venous Thromboembolism Mthfr Venous Thrombosis Comt , Mthfr vitiligo Comt Wilson disease Ahcy , Asmt withdrawal disorder Comt
