GATM

glycine amidinotransferase

Basic information

Region (hg38): 15:45361124-45402327

Links

ENSG00000171766

∙ NCBI:2628 ∙ OMIM:602360 ∙ HGNC:4175 ∙ Uniprot:P50440 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

AGAT deficiency (Definitive), mode of inheritance: AR
AGAT deficiency (Moderate), mode of inheritance: AR
Fanconi renotubular syndrome 1 (Moderate), mode of inheritance: AD
primary Fanconi syndrome (Supportive), mode of inheritance: AD
AGAT deficiency (Supportive), mode of inheritance: AR
AGAT deficiency (Strong), mode of inheritance: AR
AGAT deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi renotubular syndrome 1; Cerebral creatine deficiency syndrome 3	AD/AR	Biochemical; Renal	In Fanconi renotubular syndrome 1, individuals manifest with renal disease, and awareness may allow prompt management to help manage sequelae, and there is some evidence that creatine supplementation may be beneficial; In Cerebral creatine deficiency syndrome 3, treatment with oral creatine has been reported to possibly increase cerebral creatine, resulting in improved cognitive development	Biochemical; Neurologic; Renal	10762163; 11555793; 12468279; 16769397; 20301745; 20682460; 22386973; 23660394; 29654216

ClinVar

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

Arginine:glycine_amidinotransferase_deficiency (539 variants)
Fanconi_renotubular_syndrome_1 (86 variants)
not_provided (67 variants)
Inborn_genetic_diseases (47 variants)
not_specified (33 variants)
GATM-related_disorder (7 variants)
Intellectual_disability (2 variants)
Neurodevelopmental_disorder_with_hypotonia_and_variable_intellectual_and_behavioral_abnormalities (1 variants)
Seizure (1 variants)
Lennox-Gastaut_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GATM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001482.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	137 clinvar	3 clinvar	148
missense	1 clinvar	8 clinvar	252 clinvar	6 clinvar	3 clinvar	270
nonsense	8 clinvar	4 clinvar	1 clinvar			13
start loss						0
frameshift	6 clinvar	3 clinvar	2 clinvar			11
splice donor/acceptor (+/-2bp)	1 clinvar	7 clinvar				8
Total	16	22	263	143	6

Highest pathogenic variant AF is 0.000006572893

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GATM	protein_coding	protein_coding	ENST00000396659	9	41204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0514	0.948	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.29	144	245	0.588	0.0000135	2772
Missense in Polyphen		35	92.381	0.37887		936
Synonymous	0.609	75	82.0	0.915	0.00000446	806
Loss of Function	3.29	7	24.6	0.284	0.00000147	254

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis. {ECO:0000269|PubMed:16125225, ECO:0000269|PubMed:16614068, ECO:0000269|PubMed:16820567}.;
Disease: DISEASE: Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
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);Urea cycle and metabolism of amino groups;Metabolism of polyamines;Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Arginine Proline metabolism;creatine biosynthesis;Glycine, serine, alanine and threonine metabolism;Creatine metabolism (Consensus)

Recessive Scores

pRec: 0.207

Intolerance Scores

loftool: 0.383
rvis_EVS: -0.14
rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

pHI: 0.204
hipred: Y
hipred_score: 0.715
ghis: 0.525

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.521

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Gatm
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; reproductive system phenotype; 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); hematopoietic system phenotype;

Gene ontology

Biological process: creatine metabolic process;creatine biosynthetic process;multicellular organism development;learning or memory;muscle atrophy;positive regulation of cold-induced thermogenesis
Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;extracellular exosome
Molecular function: amidinotransferase activity;glycine amidinotransferase activity