MAT2A

methionine adenosyltransferase 2A

Basic information

Region (hg38): 2:85539167-85545281

Links

ENSG00000168906 ∙ NCBI:4144 ∙ OMIM:601468 ∙ HGNC:6904 ∙ Uniprot:P31153 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial thoracic aortic aneurysm and aortic dissection (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAT2A gene.

• Familial thoracic aortic aneurysm and aortic dissection (110 variants)
• Cardiovascular phenotype (71 variants)
• not provided (31 variants)
• not specified (24 variants)
• Vitamin K-dependent clotting factors, combined deficiency of, type 1 (8 variants)
• Isolated thoracic aortic aneurysm (2 variants)
• Vitamin K-Dependent Clotting Factors (2 variants)
• MAT2A-related condition (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAT2A 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				70	1	71
missense			41	4		45
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)				2		2
splice region			2	8		10
non coding			10	35	11	56
Total	0	0	53	111	12

Variants in MAT2A

This is a list of pathogenic ClinVar variants found in the MAT2A region.

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

Position	Type	Phenotype	Significance	ClinVar
2-85539177-G-A			Likely benign (Jun 18, 2018)
2-85539240-C-T		not specified	Likely benign (Dec 27, 2016)
2-85539253-C-G			Likely benign (Apr 06, 2018)
2-85539253-C-T		not specified	Likely benign (Dec 11, 2017)
2-85539266-A-G		not specified	Likely benign (Jun 06, 2017)
2-85539270-C-T		not specified	Likely benign (Jan 11, 2018)
2-85539273-C-T		not specified	Benign/Likely benign (Aug 19, 2023)
2-85539281-C-T		not specified	Likely benign (Dec 05, 2017)
2-85539293-C-T		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Mar 14, 2017)
2-85539295-G-A		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (May 23, 2023)
2-85539298-A-C		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Aug 24, 2019)
2-85539298-A-G		Familial thoracic aortic aneurysm and aortic dissection • Cardiovascular phenotype	Uncertain significance (Mar 04, 2024)
2-85539299-G-A		Cardiovascular phenotype • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Sep 27, 2022)
2-85539303-A-C		Familial thoracic aortic aneurysm and aortic dissection • Cardiovascular phenotype	Uncertain significance (Mar 20, 2023)
2-85539304-A-G		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Aug 23, 2020)
2-85539304-A-T		Cardiovascular phenotype	Uncertain significance (Mar 23, 2021)
2-85539308-C-T		Cardiovascular phenotype	Likely benign (Aug 25, 2023)
2-85539312-C-T		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Aug 12, 2021)
2-85539315-G-C		Cardiovascular phenotype	Uncertain significance (Sep 05, 2023)
2-85539317-G-C		Cardiovascular phenotype	Likely benign (Jan 07, 2021)
2-85539319-C-T		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Feb 07, 2021)
2-85539324-A-G		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Aug 19, 2023)
2-85539326-C-G		Cardiovascular phenotype	Uncertain significance (Jun 14, 2023)
2-85539335-C-A		Cardiovascular phenotype	Likely benign (Dec 07, 2019)
2-85539338-A-G		Cardiovascular phenotype	Likely benign (Jul 19, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAT2A	protein_coding	protein_coding	ENST00000306434	9	6116

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00154	125714	0	1	125715	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.63	69	221	0.312	0.0000114	2573
Missense in Polyphen		6	99.405	0.060359		1135
Synonymous	-0.816	83	74.1	1.12	0.00000359	771
Loss of Function	4.02	0	18.9	0.00	8.62e-7	237

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:25075345}.
• Pathway: Cysteine and methionine metabolism - Homo sapiens (human);S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Betaine Metabolism;Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;sarcosine oncometabolite pathway ;Spermidine and Spermine Biosynthesis;Selenoamino Acid Metabolism;Cystathionine Beta-Synthase Deficiency;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;Trans-sulfuration and one carbon metabolism;Methionine De Novo and Salvage Pathway;One carbon metabolism and related pathways;Methylation Pathways;Methylation;Phase II - Conjugation of compounds;methionine degradation;Biological oxidations;Metabolism;Methionine Cysteine metabolism;Methionine and cysteine metabolism;Selenoamino acid metabolism;S-adenosyl-L-methionine biosynthesis;methionine salvage cycle III;C-MYB transcription factor network;cysteine biosynthesis;superpathway of methionine degradation (Consensus)

Recessive Scores

• pRec: 0.315

Intolerance Scores

• loftool: 0.143
• rvis_EVS: -0.52
• rvis_percentile_EVS: 21.2

Haploinsufficiency Scores

• pHI: 0.812
• hipred: Y
• hipred_score: 0.728
• ghis: 0.652

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.980

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mat2a
• 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: mat2aa
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: S-adenosylmethionine biosynthetic process;one-carbon metabolic process;protein hexamerization;protein heterooligomerization;cellular response to leukemia inhibitory factor
• Cellular component: cytosol;methionine adenosyltransferase complex
• Molecular function: methionine adenosyltransferase activity;protein binding;ATP binding;identical protein binding;metal ion binding