GNMT DEFICIENCY
MCID: GLY015
MIFTS: 41

Glycine N-Methyltransferase Deficiency (GNMT DEFICIENCY)

Categories: Blood diseases, Genetic diseases, Liver diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Glycine N-Methyltransferase Deficiency

MalaCards integrated aliases for Glycine N-Methyltransferase Deficiency:

Name: Glycine N-Methyltransferase Deficiency 57 12 20 58 72 29 13 6 15 39 70
Gnmt Deficiency 57 12 20 72 54
Hypermethioninemia Due to Glycine N-Methyltransferase Deficiency 12 20 58
Hypermethioninemia Due to Gnmt Deficiency 12 20 58
Hypermethioninemia 72 70
Hepatic Methionine Adenosyltransferase Deficiency 70

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
glycine n-methyltransferase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111037
OMIM® 57 606664
ICD10 32 E72.1
ICD10 via Orphanet 33 E72.1
UMLS via Orphanet 71 C1847720
Orphanet 58 ORPHA289891
MedGen 41 C1847720
UMLS 70 C0268621 C1847720 C4048705

Summaries for Glycine N-Methyltransferase Deficiency

GARD : 20 Glycine N-methyltransferase deficiency (GNMT deficiency) is a very rare condition characterized by persistent and isolated excess levels of methionine in the blood (hypermethioninemia). The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver disease. Methionine may also be increased in urine. However, because elevated levels of methionine in the blood itself is a risk factor for development of neurological signs and symptoms, people with GNMT deficiency can have neurological problems when methionine levels are greater than 800 ?mol/L. GNMT deficiency is caused by mutations in the GNMT gene. Inheritance is autosomal recessive. Treatment is not needed in most cases.

MalaCards based summary : Glycine N-Methyltransferase Deficiency, also known as gnmt deficiency, is related to hypermethioninemia and methionine adenosyltransferase i/iii deficiency. An important gene associated with Glycine N-Methyltransferase Deficiency is GNMT (Glycine N-Methyltransferase), and among its related pathways/superpathways are Metabolism and Folate Metabolism. Affiliated tissues include liver and nk cells, and related phenotypes are hepatomegaly and elevated hepatic transaminase

Disease Ontology : 12 A hypermethioninemia characterized by autosomal recessive inheritance of persistent isolated hypermethioninemia without cystathionine beta-synthase deficiency, tyrosinemia type I, or liver disease that has material basis in homozygous or compound heterozygous mutation in the GNMT gene on chromosome 6p21.

UniProtKB/Swiss-Prot : 72 Glycine N-methyltransferase deficiency: The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases.

Wikipedia : 73 Hypermethioninemia is an excess of the amino acid methionine, in the blood. This condition can occur... more...

More information from OMIM: 606664

Related Diseases for Glycine N-Methyltransferase Deficiency

Diseases related to Glycine N-Methyltransferase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 hypermethioninemia 31.5 MAT2A MAT1A GNMT CBS BHMT AHCY
2 methionine adenosyltransferase i/iii deficiency 30.4 MAT1A CBS
3 homocystinuria 30.3 MTHFR MAT1A CBS BHMT
4 homocysteinemia 29.8 MTHFR CBS BHMT AHCY
5 hypermethioninemia due to adenosine kinase deficiency 11.7
6 hypermethioninemia with s-adenosylhomocysteine hydrolase deficiency 11.7
7 methionine adenosyltransferase deficiency 11.0
8 fatty liver disease 10.3
9 homocystinuria due to cystathionine beta-synthase deficiency 10.2
10 tyrosinemia 10.2
11 alpha-methylacetoacetic aciduria 10.2
12 hypertrichosis universalis congenita, ambras type 10.1 MAT2A MAT1A
13 type 2 diabetes mellitus 10.1
14 niemann-pick disease, type c2 10.1
15 non-alcoholic fatty liver disease 10.1
16 glucose intolerance 10.1
17 liver disease 10.1
18 cholestasis 10.1
19 choline deficiency disease 10.0 MTHFR BHMT AHCY
20 methylmalonic acidemia and homocysteinemia, cblx type 10.0 MTHFR BHMT
21 amino acid metabolic disorder 10.0 MTHFR BHMT AHCY
22 biliary atresia 10.0
23 inherited metabolic disorder 10.0
24 dimethylglycine dehydrogenase deficiency 10.0 SARDH DMGDH
25 lens subluxation 9.9 MTHFR CBS
26 sarcosinemia 9.9 SARDH DMGDH
27 myositis 9.8
28 triiodothyronine receptor auxiliary protein 9.8
29 phenylketonuria 9.8
30 tyrosinemia, type i 9.8
31 autosomal recessive non-syndromic intellectual disability 9.8
32 obstructive jaundice 9.8
33 toxic shock syndrome 9.8
34 vascular disease 9.8
35 pharyngitis 9.8
36 liver cirrhosis 9.8
37 impetigo 9.8
38 mitochondrial disorders 9.8
39 biliary hypoplasia 9.8
40 chromosomal triplication 9.8
41 encephalopathy 9.8
42 hypotonia 9.8
43 streptococcal toxic-shock syndrome 9.8

Graphical network of the top 20 diseases related to Glycine N-Methyltransferase Deficiency:



Diseases related to Glycine N-Methyltransferase Deficiency

Symptoms & Phenotypes for Glycine N-Methyltransferase Deficiency

Human phenotypes related to Glycine N-Methyltransferase Deficiency:

31
# Description HPO Frequency HPO Source Accession
1 hepatomegaly 31 HP:0002240
2 elevated hepatic transaminase 31 HP:0002910
3 hypermethioninemia 31 HP:0003235

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Liver:
hepatomegaly

Laboratory Abnormalities:
hypermethioninemia
elevated transaminases

Clinical features from OMIM®:

606664 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Glycine N-Methyltransferase Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 9.23 ADK BHMT GNMT MAT1A MTAP MTHFR

Drugs & Therapeutics for Glycine N-Methyltransferase Deficiency

Search Clinical Trials , NIH Clinical Center for Glycine N-Methyltransferase Deficiency

Genetic Tests for Glycine N-Methyltransferase Deficiency

Genetic tests related to Glycine N-Methyltransferase Deficiency:

# Genetic test Affiliating Genes
1 Glycine N-Methyltransferase Deficiency 29 GNMT

Anatomical Context for Glycine N-Methyltransferase Deficiency

MalaCards organs/tissues related to Glycine N-Methyltransferase Deficiency:

40
Liver, Nk Cells

Publications for Glycine N-Methyltransferase Deficiency

Articles related to Glycine N-Methyltransferase Deficiency:

(show all 21)
# Title Authors PMID Year
1
Glycine N -methyltransferase deficiency: a new patient with a novel mutation. 20 54 6 57 61
14739680 2003
2
Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia. 61 54 6 57
11596649 2001
3
Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. 57 6
11810299 2002
4
Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver. 54 57
17937387 2007
5
Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders? 20 61
27207470 2017
6
Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. 20
27671891 2017
7
Inherited disorders in the conversion of methionine to homocysteine. 61 54
19585268 2009
8
Characterization of reduced expression of glycine N-methyltransferase in cancerous hepatic tissues using two newly developed monoclonal antibodies. 54 61
12566990 2003
9
Familial hypermethioninemia partially responsive to dietary restriction. 20
2380820 1990
10
Targeted and untargeted metabolomics provide insight into the consequences of glycine-N-methyltransferase deficiency including the novel finding of defective immune function. 61
32951289 2020
11
Tumor suppressor gene glycine N-methyltransferase and its potential in liver disorders and hepatocellular carcinoma. 61
31170416 2019
12
MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis. 61
30237481 2018
13
Glycine N-methyltransferase deficiency in female mice impairs insulin signaling and promotes gluconeogenesis by modulating the PI3K/Akt pathway in the liver. 61
27716281 2016
14
Methionine and S-adenosylmethionine levels are critical regulators of PP2A activity modulating lipophagy during steatosis. 61
26394163 2016
15
Role of glycine N-methyltransferase in the regulation of T-cell responses in experimental autoimmune encephalomyelitis. 61
25535034 2015
16
TRAIL-producing NK cells contribute to liver injury and related fibrogenesis in the context of GNMT deficiency. 61
25531568 2015
17
The multi-functional roles of GNMT in toxicology and cancer. 61
23147572 2013
18
Glycine N-methyltransferase deficiency affects Niemann-Pick type C2 protein stability and regulates hepatic cholesterol homeostasis. 61
22183894 2012
19
Hypermethioninemias of genetic and non-genetic origin: A review. 61
21308989 2011
20
Deficiency of glycine N-methyltransferase results in deterioration of cellular defense to stress in mouse liver. 61
21137059 2010
21
Methyl balance and transmethylation fluxes in humans. 61
17209172 2007

Variations for Glycine N-Methyltransferase Deficiency

ClinVar genetic disease variations for Glycine N-Methyltransferase Deficiency:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CNPY3-GNMT , GNMT NM_018960.6(GNMT):c.149T>C (p.Leu50Pro) SNV Pathogenic 4169 rs121907888 GRCh37: 6:42928654-42928654
GRCh38: 6:42960916-42960916
2 CNPY3-GNMT , GNMT NM_018960.6(GNMT):c.422A>G (p.Asn141Ser) SNV Pathogenic 218931 rs864321678 GRCh37: 6:42930587-42930587
GRCh38: 6:42962849-42962849
3 PEX6 , CNPY3-GNMT , GNMT NM_018960.6(GNMT):c.529C>A (p.His177Asn) SNV Pathogenic 4170 rs121907889 GRCh37: 6:42930887-42930887
GRCh38: 6:42963149-42963149
4 CNPY3-GNMT , GNMT NM_018960.6(GNMT):c.888_*3del (p.Ter296CysextTer?) Deletion Pathogenic 1030685 GRCh37: 6:42931442-42931445
GRCh38: 6:42963704-42963707
5 CNPY3-GNMT , GNMT NM_018960.6(GNMT):c.454G>A (p.Asp152Asn) SNV Uncertain significance 1030683 GRCh37: 6:42930812-42930812
GRCh38: 6:42963074-42963074
6 CNPY3-GNMT , GNMT NM_018960.6(GNMT):c.469C>T (p.Arg157Trp) SNV Uncertain significance 1030684 GRCh37: 6:42930827-42930827
GRCh38: 6:42963089-42963089

UniProtKB/Swiss-Prot genetic disease variations for Glycine N-Methyltransferase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 GNMT p.Leu50Pro VAR_012766 rs121907888
2 GNMT p.His177Asn VAR_012767 rs121907889
3 GNMT p.Asn141Ser VAR_019840 rs864321678

Expression for Glycine N-Methyltransferase Deficiency

Search GEO for disease gene expression data for Glycine N-Methyltransferase Deficiency.

Pathways for Glycine N-Methyltransferase Deficiency

Pathways related to Glycine N-Methyltransferase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.75 ST20-MTHFS SARDH NPC2 MTHFR MTAP MAT2A
2
Show member pathways
12.07 MTHFR MAT1A CBS AHCY
3
Show member pathways
12.03 MTHFR MAT2A MAT1A CBS
4 11.59 FTCD CBS BHMT
5
Show member pathways
11.53 MTAP MAT2A MAT1A CBS BHMT AHCY
6
Show member pathways
11.38 ST20-MTHFS MTHFR MAT2A MAT1A FTCD CBS
7
Show member pathways
11.27 SARDH GNMT DMGDH CBS BHMT
8
Show member pathways
10.96 MAT2A MAT1A CBS
9
Show member pathways
10.68 MAT2A MAT1A
10 10.27 MTHFR CBS

GO Terms for Glycine N-Methyltransferase Deficiency

Cellular components related to Glycine N-Methyltransferase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.5 SOCS2 PREX2 PEX6 MTHFR MTAP MAT2A

Biological processes related to Glycine N-Methyltransferase Deficiency according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cellular protein modification process GO:0006464 9.7 LCMT1 GNMT ADPRH
2 one-carbon metabolic process GO:0006730 9.62 MAT2A MAT1A GNMT AHCY
3 protein methylation GO:0006479 9.54 LCMT1 BHMT
4 methionine biosynthetic process GO:0009086 9.51 MTHFR BHMT
5 tetrahydrofolate interconversion GO:0035999 9.49 MTHFR FTCD
6 homocysteine metabolic process GO:0050667 9.48 MTHFR CBS
7 methionine metabolic process GO:0006555 9.46 MTHFR GNMT
8 purine ribonucleoside salvage GO:0006166 9.43 MTAP ADK
9 S-adenosylmethionine metabolic process GO:0046500 9.43 MTHFR GNMT BHMT
10 S-adenosylmethionine biosynthetic process GO:0006556 9.4 MAT2A MAT1A
11 amino-acid betaine catabolic process GO:0006579 9.37 DMGDH BHMT
12 choline catabolic process GO:0042426 9.33 SARDH DMGDH BHMT
13 sulfur amino acid metabolic process GO:0000096 9.13 MAT1A BHMT AHCY
14 methylation GO:0032259 9.1 MAT2A MAT1A LCMT1 GNMT BHMT AHCY

Molecular functions related to Glycine N-Methyltransferase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.61 SARDH MTAP MAT2A MAT1A LCMT1 GNMT
2 S-adenosyl-L-methionine binding GO:1904047 9.32 GNMT CBS
3 folic acid binding GO:0005542 9.26 GNMT FTCD
4 modified amino acid binding GO:0072341 9.16 MTHFR CBS
5 methionine adenosyltransferase activity GO:0004478 8.62 MAT2A MAT1A

Sources for Glycine N-Methyltransferase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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