GAMT guanidinoacetate N-methyltransferase [Homo sapiens (human)] - Gene

Summary

Official Symbol: GAMTprovided by HGNC
Official Full Name: guanidinoacetate N-methyltransferaseprovided by HGNC
Primary source: HGNC:HGNC:4136
See related: Ensembl:ENSG00000130005 MIM:601240; AllianceGenome:HGNC:4136
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PIG2; CCDS2; TP53I2; HEL-S-20
Summary: The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene. Pseudogenes of this gene are found on chromosomes 2 and 13. [provided by RefSeq, Feb 2012]
Expression: Broad expression in liver (RPKM 37.8), pancreas (RPKM 12.2) and 15 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (1397026..1401542, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (1367024..1371540, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (1397025..1401541, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of novel variations in SLC6A8 and GAMT genes causing cerebral creatine deficiency syndrome.
Title: Identification of novel variations in SLC6A8 and GAMT genes causing cerebral creatine deficiency syndrome.
Elastic net-based identification of GAMT as potential diagnostic marker for early-stage gastric cancer.
Title: Elastic net-based identification of GAMT as potential diagnostic marker for early-stage gastric cancer.
Here, we report 9 and 10-year-old cousins with GAMT deficiency caused by a novel mutation who both exhibited neurodevelopmental retardation, seizures, behavioral problems, and autism that began during early infancy. A novel nonsense mutation in the GAMT gene that caused cessation of synthesis of the protein encoded by this gene was identified in these patients.
Title: A novel mutation in two cousins with guanidinoacetate methyltransferase (GAMT) deficiency presented with autism.
We unveil PFN2 and GAMT as molecular determinants of Charcot-Marie-Tooth type 2 neuropathy, with possible indications of the role of PFN2 in the pathogenesis and disease progression.
Title: PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease.
Measurements of creatine and guanidinoacetate in plasma are recommended for the diagnosis of AGAT and GAMT deficiency.Definitive confirmation of the diagnosis requires DNA sequencing of the appropriate gene and (if molecular analysis is ambiguous) measurement of AGAT or GAMT enzyme activity or of CRTR-mediated transport
Title: Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics.
Data suggest that creatine is provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvement of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. [REVIEW]
Title: Creatine biosynthesis and transport in health and disease.
As early diagnosis results in normal neurodevelopmental outcome, GAMT deficiency should be included in newborn screening programs to diagnose individuals at the asymptomatic stage of the disease
Title: Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene.
The estimated incidence of GAMT deficiency is 1:250,000 newborns based on our pilot study.
Title: A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene.
Study reports six novel pathogenic mutations in GAMT gene in patients with Guanidinoacetate methyltransferase deficiency.
Title: Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene.
Two novel heterozygous variants with sequence deletion and sequence insertion in the GAMT gene have been identified in newborns with guanidinoacetate methyltransferase deficiency.
Title: Guanidinoacetate methyltransferase deficiency: first steps to newborn screening for a treatable neurometabolic disease.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Deficiency of guanidinoacetate methyltransferase MedGen: C0574080 OMIM: 612736 GeneReviews: Creatine Deficiency Disorders	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GAMT__6784 (e-PCR)
- UniSTS:466198

D15S702E (e-PCR)
- UniSTS:151609

RH79693 (e-PCR)
- UniSTS:89031

SGC31985 (e-PCR)
- UniSTS:99830

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanidinoacetate N-methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanidinoacetate N-methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables methyltransferase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in animal organ morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in creatine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in creatine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in creatine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in creatine metabolic process	TAS Traceable Author Statement more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in muscle contraction	TAS Traceable Author Statement more info	PubMed
involved_in regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: guanidinoacetate N-methyltransferase

Names: epididymis secretory protein Li 20

NP_000147.1

EC 2.1.1.2

NP_620279.1

EC 2.1.1.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009785.1 RefSeqGene

Range

5012..9528

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000156.6 → NP_000147.1 guanidinoacetate N-methyltransferase isoform a

See identical proteins and their annotated locations for NP_000147.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longer transcript but encodes the shorter isoform (a).

Source sequence(s)

AC005329, BC016760

Consensus CDS

CCDS12064.1

UniProtKB/Swiss-Prot

A8K0A0, Q14353, Q53Y34, Q8WVJ1

UniProtKB/TrEMBL

A0A1W2PR36, V9HWB2

Related

ENSP00000252288.1, ENST00000252288.8

Conserved Domains (1) summary

cd02440
Location:63 → 166

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...
NM_138924.3 → NP_620279.1 guanidinoacetate N-methyltransferase isoform b

See identical proteins and their annotated locations for NP_620279.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks the 3'-most exon and fails to utilize the 3' splice donor site of the penultimate exon as compared to transcript variant 1. As a result, variant 2 encodes isoform b, which is longer and contains a distinct C-terminus, compared to isoform a. PMID:26003046 notes that protein expression was not detected for this variant by Western blot analysis using a GFP fusion construct and the experimental conditions reported in the publication.

Source sequence(s)

AC005329, AK289465, BM994704

Consensus CDS

CCDS45897.1

UniProtKB/Swiss-Prot

Q14353

Related

ENSP00000403536.2, ENST00000447102.8

Conserved Domains (1) summary

cd02440
Location:63 → 166

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...