GNMT (glycine N-methyltransferase)

Gene

• Entrez ID: 27232
• Gene name: Glycine N-methyltransferase
• Gene symbol: GNMT
• Synonyms (NCBI Gene): HEL-S-182mP
• Chromosome: 6
• Chromosome location: 6p21.1
• Summary: The protein encoded by this gene is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine (along with glycine) to S-adenosyl-L-homocysteine and sarcosine. This protein is found in the cytoplasm and acts as a homotetramer. Defects in this gene

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016781	hsa-miR-335-5p	Microarray	18185580
MIRT2437451	hsa-miR-1291	CLIP-seq
MIRT2437452	hsa-miR-3151	CLIP-seq
MIRT2437453	hsa-miR-328	CLIP-seq
MIRT2437454	hsa-miR-3650	CLIP-seq
MIRT2437455	hsa-miR-4283	CLIP-seq
MIRT2437456	hsa-miR-4447	CLIP-seq
MIRT2437457	hsa-miR-4472	CLIP-seq
MIRT2437458	hsa-miR-4489	CLIP-seq
MIRT2437459	hsa-miR-485-5p	CLIP-seq
MIRT2437460	hsa-miR-491-5p	CLIP-seq
MIRT2437451	hsa-miR-1291	CLIP-seq
MIRT2437452	hsa-miR-3151	CLIP-seq
MIRT2437453	hsa-miR-328	CLIP-seq
MIRT2437454	hsa-miR-3650	CLIP-seq
MIRT2437455	hsa-miR-4283	CLIP-seq
MIRT2437456	hsa-miR-4447	CLIP-seq
MIRT2437457	hsa-miR-4472	CLIP-seq
MIRT2437458	hsa-miR-4489	CLIP-seq
MIRT2437459	hsa-miR-485-5p	CLIP-seq
MIRT2437460	hsa-miR-491-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
AR	Unknown	23997240

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	16189514, 21988832, 26871637, 31515488, 32296183
GO:0005542	Function	Folic acid binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005977	Process	Glycogen metabolic process	IEA
GO:0006111	Process	Regulation of gluconeogenesis	IBA
GO:0006111	Process	Regulation of gluconeogenesis	IEA
GO:0006555	Process	Methionine metabolic process	IEA
GO:0006730	Process	One-carbon metabolic process	IBA
GO:0006730	Process	One-carbon metabolic process	IEA
GO:0008168	Function	Methyltransferase activity	IEA
GO:0016594	Function	Glycine binding	IBA
GO:0016594	Function	Glycine binding	IDA	15340920
GO:0016594	Function	Glycine binding	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0017174	Function	Glycine N-methyltransferase activity	IBA
GO:0017174	Function	Glycine N-methyltransferase activity	IDA	15340920
GO:0017174	Function	Glycine N-methyltransferase activity	IEA
GO:0032259	Process	Methylation	IEA
GO:0042802	Function	Identical protein binding	IBA
GO:0042802	Function	Identical protein binding	IPI	16189514, 25502805, 26871637, 31515488
GO:0046498	Process	S-adenosylhomocysteine metabolic process	IBA
GO:0046500	Process	S-adenosylmethionine metabolic process	IBA
GO:0046500	Process	S-adenosylmethionine metabolic process	IDA	15340920
GO:0046500	Process	S-adenosylmethionine metabolic process	IEA
GO:0051289	Process	Protein homotetramerization	IBA
GO:0051289	Process	Protein homotetramerization	IEA
GO:0051289	Process	Protein homotetramerization	IPI	15340920
GO:1901052	Process	Sarcosine metabolic process	IBA
GO:1904047	Function	S-adenosyl-L-methionine binding	IBA

Other IDs

• MIM: 606628
• HGNC: 4415
• e!Ensembl: ENSG00000124713

Protein

• UniProt ID: Q14749
• Protein name: Glycine N-methyltransferase (EC 2.1.1.20)
• Protein function: Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy), a reaction regulated by the binding of 5-methyltetrahydrofolate.
• PDB: 1R74, 2AZT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13649	Methyltransf_25	61 → 171	Methyltransferase domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed only in liver, pancreas, and prostate. {ECO:0000269|PubMed:9495250}.
• Sequence:

  MVDSVYRTRSLGVAAEGLPDQYADGEAARVWQLYIGDTRSRTAEYKAWLLGLLRQHGCQR
  VLDVACGTGVDSIMLVEEGFSVTSVDASDKMLKYALKERWNRRHEPAFDKWVIEEANWMT
  LDKDVPQSAEGGFDAVICLGNSFAHLPDCKGDQSEHRLALKNIASMVRAGGLLVIDHRNY
  DHILSTGCAPPGKNIYYKSDLTKDVTTSVLIVNNKAHMVTLDYTVQVPGAGQDGSPGLSK
  FRLSYYPHCLASFTELLQAAFGGKCQHSVLGDFKPYKPGQTYIPCYFIHVLKRTD

• Sequence length: 295

Pathways

KEGG:

Glycine, serine and threonine metabolism
Cysteine and methionine metabolism
One carbon pool by folate
Metabolic pathways

Reactome:

Glyoxylate metabolism and glycine degradation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Glycine N-methyltransferase deficiency	Pathogenic	rs121907888, rs864321678	RCV000004386 RCV000203283	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC PERSISTENT HEPATITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEFICIENCY OF S-ADENOSYLHOMOCYSTEINE HYDROLASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDER OF SULFUR-BEARING AMINO ACID METABOLISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GNMT-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATIC METHIONINE ADENOSYLTRANSFERASE DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATITIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATITIS, CHRONIC	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERHOMOCYSTEINEMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NONALCOHOLIC STEATOHEPATITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEROXISOME BIOGENESIS DISORDER 4B	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of pancreas	Pancreatic adenocarcinoma	BEFREE	25560641		★☆☆☆☆ Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	25560641		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24884785		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	24884785, 37747033	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	21572396	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	21411609, 30138348, 32290267, 35008908	Associate	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	LHGDN	18624901		★☆☆☆☆ Found in Text Mining only
Cholestasis	Cholestasis	BEFREE	30237481		★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	30237481		★☆☆☆☆ Found in Text Mining only
Cleft Lip with or without Cleft Palate	Cleft Lip With Or Without Cleft Palate	BEFREE	30318092		★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	28264803		★☆☆☆☆ Found in Text Mining only
Dysplastic Nevus	Dysplastic Nevus	BEFREE	24999589		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	30850319		★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	31199045, 31668391		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	30115977, 30217986, 30237481		★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	28264803	Associate	★☆☆☆☆ Found in Text Mining only
Hepatic methionine adenosyltransferase deficiency	Hepatic Methionine Adenosyltransferase Deficiency	CTD_human_DG	11596649, 11810299		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholesterolemia	Hypercholesterolemia	BEFREE	22183894		★☆☆☆☆ Found in Text Mining only
Hyperhomocysteinemia	Hyperhomocysteinemia	CTD_human_DG	16317120		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypermethioninemia due to deficiency of glycine N-methyltransferase	Glycine N-methyltransferase deficiency	CLINGEN_DG	11131452, 11596649, 14739680, 16779654, 17937387, 27207470		★☆☆☆☆ Found in Text Mining only
Hypermethioninemia due to deficiency of glycine N-methyltransferase	Glycine N-methyltransferase deficiency	CTD_human_DG	11596649, 11810299		★☆☆☆☆ Found in Text Mining only
Hypermethioninemia due to deficiency of glycine N-methyltransferase	Glycine N-methyltransferase deficiency	UNIPROT_DG	11810299, 14739680		★☆☆☆☆ Found in Text Mining only
Hypermethioninemia due to deficiency of glycine N-methyltransferase	Glycine N-methyltransferase deficiency	GENOMICS_ENGLAND_DG	14739680		★☆☆☆☆ Found in Text Mining only
Hypermethioninemia due to deficiency of glycine N-methyltransferase	Glycine N-methyltransferase deficiency	ORPHANET_DG	19585268		★☆☆☆☆ Found in Text Mining only
Hypermethioninemia due to deficiency of glycine N-methyltransferase	Glycine N-methyltransferase deficiency	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypermethioninemia due to glycine N-methyltransferase deficiency	Hypermethioninemia	Orphanet			★☆☆☆☆ Found in Text Mining only
Inborn Errors of Metabolism	Inborn Errors Of Metabolism	BEFREE	30681159		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	BEFREE	29725048		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	21790528		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	10843803, 12566309, 12566990, 17332283, 19035462, 19146867, 21145824, 22183894, 22434528, 22687285, 23073625, 23474979, 23475283, 23749938, 23922098, 27153064, 28205209, 30115977, 30217986, 30237481, 30760754, 30850319, 31086990, 31170416, 9495250		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	LHGDN	12566309, 19146867		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	CTD_human_DG	19146867, 31086990		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	30217986, 30237481		★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	30138348	Associate	★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	LHGDN	19035462		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Liver neoplasms	Liver neoplasms	CTD_human_DG	21137059		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Liver neoplasms	Liver neoplasms	BEFREE	23922098, 30217986, 30850319, 30987732		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	BEFREE	24884785		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	12566309, 15150120, 19035462, 27153064, 31086990, 9495250		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	CTD_human_DG	21137059		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	17332283, 22850906, 23633921, 24800880		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	17332283		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23883094		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	24999589		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	24999589	Associate	★☆☆☆☆ Found in Text Mining only
Metastatic Prostate Carcinoma	Metastatic Prostate Carcinoma	BEFREE	24800880		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	12566309, 17332283, 19035462, 19146867, 21411609, 23475283, 23749938, 23883094, 23922098, 24800880, 25560641, 27153064, 30115977, 31170416		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	20684516, 22183894, 25576488, 31086990, 31668391		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	CTD_human_DG	31086990		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	CTD_human_DG	31086990		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	BEFREE	31199045, 31668391		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Oropharyngeal Neoplasms	Oropharyngeal neoplasm	Pubtator	32415241	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	31706267	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	17332283, 22850906, 23633921, 24800880		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	17332283		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	19212411, 21572396, 23883094, 23997240, 24800880, 28033303	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	23633921		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
S-adenosylhomocysteine hydrolase deficiency	S-Adenosylhomocysteine Hydrolase Deficiency	CTD_human_DG	11596649, 11810299		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	22264868		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	30850319		★☆☆☆☆ Found in Text Mining only
Visceral myopathy familial external ophthalmoplegia	Visceral neuropathy	Pubtator	22137549	Associate	★☆☆☆☆ Found in Text Mining only