GAMT

guanidinoacetate N-methyltransferase, the group of 7BS small molecule methyltransferases

Basic information

Region (hg38): 19:1397026-1401570

Links

ENSG00000130005

∙ NCBI:2593 ∙ OMIM:601240 ∙ HGNC:4136 ∙ Uniprot:Q14353 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

guanidinoacetate methyltransferase deficiency (Definitive), mode of inheritance: AR
guanidinoacetate methyltransferase deficiency (Strong), mode of inheritance: AR
guanidinoacetate methyltransferase deficiency (Definitive), mode of inheritance: AR
guanidinoacetate methyltransferase deficiency (Supportive), mode of inheritance: AR
guanidinoacetate methyltransferase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebral creatine deficiency syndrome 2 (Guanidinoacetate methyltransferase deficiency)	AR	Biochemical	The condition involves neurologic sequelae, and medical (eg, with creatine-monohydrate, L-ornithine, and/or sodium benzoate) as well as dietary (eg, with ornithine supplementation and protein/arginine restriction) has been reported to increase cerebral creatine, resulting in improvement or stabilization of clinical manifestations in all symptomatic individuals	Biochemical; Neurologic	7808840; 8651275; 9386672; 11196109; 15651030; 17171576; 17336114; 19027335; 20301745; 23031365; 24268530; 34389248

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GAMT gene.

Cerebral creatine deficiency syndrome (45 variants)
Deficiency of guanidinoacetate methyltransferase (31 variants)
not provided (9 variants)
Inborn genetic diseases (6 variants)
GAMT-related disorder (2 variants)
Abnormality of the nervous system (1 variants)
not specified (1 variants)
See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAMT gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1 clinvar	7 clinvar	134 clinvar	2 clinvar	144
missense	7 clinvar	23 clinvar	194 clinvar	2 clinvar	3 clinvar	229
nonsense	14 clinvar	9 clinvar	2 clinvar			25
start loss	2	1				3
frameshift	26 clinvar	22 clinvar	3 clinvar			51
splice donor/acceptor (+/-2bp)	2 clinvar	10 clinvar	1 clinvar			13
Total	51	66	207	136	5

Highest pathogenic variant AF is 0.000164182

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAMT	protein_coding	protein_coding	ENST00000447102	5	4479

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00948	0.828	125517	0	8	125525	0.0000319

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0872	153	150	1.02	0.00000858	1699
Missense in Polyphen		46	46.021	0.99954		506
Synonymous	0.0246	64	64.3	0.996	0.00000399	550
Loss of Function	1.11	4	7.24	0.553	3.11e-7	84

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000134	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000363	0.0000353
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Converts guanidinoacetate to creatine, using S- adenosylmethionine as the methyl donor (PubMed:26003046, PubMed:24415674, PubMed:26319512). Important in nervous system development (PubMed:24415674). {ECO:0000269|PubMed:24415674, ECO:0000269|PubMed:26003046, ECO:0000269|PubMed:26319512}.;
Pathway: Arginine and proline metabolism - Homo sapiens (human);Glycine, serine and threonine metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Prolinemia Type II;Prolidase Deficiency (PD);Arginine and Proline Metabolism;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Dihydropyrimidine Dehydrogenase Deficiency (DHPD);MECP2 and Associated Rett Syndrome;Urea cycle and metabolism of amino groups;Metabolism of polyamines;Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;Arginine Proline metabolism;creatine biosynthesis;Creatine metabolism (Consensus)

Recessive Scores

pRec: 0.189

Intolerance Scores

loftool: 0.140
rvis_EVS: -0.09
rvis_percentile_EVS: 46.74

Haploinsufficiency Scores

pHI: 0.0969
hipred: N
hipred_score: 0.170
ghis: 0.520

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.955

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Gamt
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype;

Gene ontology

Biological process: creatine metabolic process;creatine biosynthetic process;muscle contraction;spermatogenesis;animal organ morphogenesis;methylation;regulation of multicellular organism growth;S-adenosylhomocysteine metabolic process;S-adenosylmethionine metabolic process
Cellular component: nucleus;cytoplasm;cytosol
Molecular function: methyltransferase activity;S-adenosylmethionine-dependent methyltransferase activity;guanidinoacetate N-methyltransferase activity