MAT1A

methionine adenosyltransferase 1A

Basic information

Region (hg38): 10:80271820-80289658

Links

ENSG00000151224 ∙ NCBI:4143 ∙ OMIM:610550 ∙ HGNC:6903 ∙ Uniprot:Q00266 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• methionine adenosyltransferase deficiency (Strong), mode of inheritance: AR
• methionine adenosyltransferase deficiency (Strong), mode of inheritance: AD
• methionine adenosyltransferase deficiency (Strong), mode of inheritance: AR
• methionine adenosyltransferase deficiency (Supportive), mode of inheritance: AR
• methionine adenosyltransferase deficiency (Strong), mode of inheritance: AR
• methionine adenosyltransferase deficiency (Strong), mode of inheritance: AD
• methionine adenosyltransferase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methionine adenosyltransferase I/III deficiency	AD/AR	Biochemical	While the disorders frequently do not have severe sequelae, and therapy may not be required for many individuals, in some, dietary measures (eg, methionine restriction) may be beneficial; AdoMet therapy has also been described as beneficial	Biochemical; Neurologic	1191305; 7229751; 7271238; 3812486; 3339126; 1683972; 1527987; 7573050; 7560086; 8770875; 9042912; 9482646; 12705496

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAT1A gene.

• Hepatic methionine adenosyltransferase deficiency (16 variants)
• not provided (6 variants)
• MAT1A-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAT1A gene is commonly pathogenic or not.

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			3	41	6	50
missense	10	8	127			145
nonsense	3		1			4
start loss						0
frameshift	4					4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			6	7		13
non coding			54	25	40	119
Total	18	10	187	66	46

Highest pathogenic variant AF is 0.0000197

Variants in MAT1A

This is a list of pathogenic ClinVar variants found in the MAT1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-80271857-G-A		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 12, 2018)
10-80271923-A-G		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80271961-C-T		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80272040-A-G		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 12, 2018)
10-80272054-C-T		Hepatic methionine adenosyltransferase deficiency	Likely benign (Jan 13, 2018)
10-80272090-A-G		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80272108-G-A		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Apr 27, 2017)
10-80272120-C-G		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80272181-C-CCCAGCCTGAA		Hepatic methionine adenosyltransferase deficiency	Benign (Jun 14, 2016)
10-80272399-C-T		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 12, 2018)
10-80272483-C-T		Hepatic methionine adenosyltransferase deficiency	Benign (Jan 13, 2018)
10-80272484-A-G		Hepatic methionine adenosyltransferase deficiency	Benign (Jan 12, 2018)
10-80272489-C-G		Hepatic methionine adenosyltransferase deficiency	Benign (Jan 13, 2018)
10-80272513-A-G		Hepatic methionine adenosyltransferase deficiency	Likely benign (Jan 13, 2018)
10-80272574-A-G		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80272575-C-T		Hepatic methionine adenosyltransferase deficiency	Benign (Jan 12, 2018)
10-80272589-G-C		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80272681-G-C		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
10-80272689-G-C		Hepatic methionine adenosyltransferase deficiency	Benign (Jan 13, 2018)
10-80272703-G-A		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 12, 2018)
10-80272723-A-G		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 12, 2018)
10-80272752-C-T		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jan 12, 2018)
10-80272760-G-T		Hepatic methionine adenosyltransferase deficiency	Uncertain significance (Jun 14, 2016)
10-80272785-TG-T		Hepatic methionine adenosyltransferase deficiency	Benign (Jun 14, 2016)
10-80272799-T-A		Hepatic methionine adenosyltransferase deficiency	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAT1A	protein_coding	protein_coding	ENST00000372213	9	17865

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000810	0.985	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	166	238	0.698	0.0000157	2576
Missense in Polyphen		53	108.73	0.48745		1142
Synonymous	-0.912	107	95.7	1.12	0.00000708	788
Loss of Function	2.16	8	17.8	0.449	8.66e-7	208

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000879	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.000135	0.000131
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate. {ECO:0000269|PubMed:10677294}.
• Disease: DISEASE: Methionine adenosyltransferase deficiency (MATD) [MIM:250850]: An inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic symptoms may be present in rare cases with severe loss of methionine adenosyltransferase activity. {ECO:0000269|PubMed:10677294, ECO:0000269|PubMed:7560086, ECO:0000269|PubMed:8770875, ECO:0000269|PubMed:9042912}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cysteine and methionine metabolism - Homo sapiens (human);Vitamin B12 Metabolism;Folate Metabolism;One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;Methionine De Novo and Salvage Pathway;One carbon metabolism and related pathways;Ethanol effects on histone modifications;Methylation Pathways;Methylation;Phase II - Conjugation of compounds;Metabolism of amino acids and derivatives;methionine degradation;Biological oxidations;Metabolism;Methionine Cysteine metabolism;Selenoamino acid metabolism;Metabolism of ingested SeMet, Sec, MeSec into H2Se;S-adenosyl-L-methionine biosynthesis;methionine salvage cycle III;Sulfur amino acid metabolism;cysteine biosynthesis;superpathway of methionine degradation (Consensus)

Recessive Scores

• pRec: 0.376

Intolerance Scores

• loftool: 0.0748
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.77

Haploinsufficiency Scores

• pHI: 0.916
• hipred: Y
• hipred_score: 0.707
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.770

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mat1a
• Phenotype: liver/biliary system phenotype; homeostasis/metabolism phenotype; immune system phenotype

Gene ontology

• Biological process: sulfur amino acid metabolic process;selenium compound metabolic process;S-adenosylmethionine biosynthetic process;one-carbon metabolic process;methionine catabolic process;methylation;protein homotetramerization
• Cellular component: cytosol
• Molecular function: methionine adenosyltransferase activity;ATP binding;identical protein binding;metal ion binding;selenomethionine adenosyltransferase activity