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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 15.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_000156.6	NP_000147.1	6	yes	-
ENST00000252288.8	ENSP00000252288.1	6	yes	-
NM_138924.3	NP_620279.1	5	-	-
ENST00000447102.8	ENSP00000403536.2	5	-	-

Phenotypes

GenCC

Source: genCC

• guanidinoacetate methyltransferase deficiency (Definitive), mode of inheritance: AR
• guanidinoacetate methyltransferase deficiency (Definitive), mode of inheritance: AR
• guanidinoacetate methyltransferase deficiency (Strong), 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 (534 variants)
• Deficiency_of_guanidinoacetate_methyltransferase (252 variants)
• not_provided (132 variants)
• Inborn_genetic_diseases (95 variants)
• not_specified (55 variants)
• GAMT-related_disorder (19 variants)
• Intellectual_disability (2 variants)
• Parkinson_disease,_late-onset (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Guanidinoacetate_Methyltransferase_(GAMT)_Deficiency (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: NM_000156.6. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	11	149	2	164
missense	14	27	216	7	4	268
nonsense	15	11	2			28
start loss	2	2				4
frameshift	28	28	3			59
splice donor/acceptor (+/-2bp)	4	12	1			17
Total	64	81	233	156	6

Highest pathogenic variant AF is 0.00045182844

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
		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

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

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