MTHFD2

methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase

Basic information

Region (hg38): 2:74186172-74217565

Links

ENSG00000065911

∙ NCBI:10797 ∙ OMIM:604887 ∙ HGNC:7434 ∙ Uniprot:P13995 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTHFD2 gene.

not_specified (43 variants)
not_provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTHFD2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006636.4. 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				1 clinvar		1
missense			41 clinvar	2 clinvar		43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	3	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTHFD2	protein_coding	protein_coding	ENST00000394053	8	19004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00240	0.983	124831	0	20	124851	0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.481	172	191	0.902	0.00000921	2250
Missense in Polyphen		57	72.089	0.79069		946
Synonymous	-0.384	75	70.9	1.06	0.00000359	719
Loss of Function	2.14	7	16.3	0.429	9.42e-7	182

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000240	0.000240
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000166
Finnish	0.000232	0.000232
European (Non-Finnish)	0.0000266	0.0000265
Middle Eastern	0.000167	0.000166
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency. {ECO:0000269|PubMed:16100107}.;
Pathway: One carbon pool by folate - Homo sapiens (human);Folate malabsorption, hereditary;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;Folate Metabolism;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;Nucleotide Metabolism;Folate metabolism;Metabolism;folate transformations I;Metabolism of folate and pterines;histidine degradation;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Vitamin B9 (folate) metabolism;tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate (Consensus)

Recessive Scores

pRec: 0.255

Intolerance Scores

loftool: 0.447
rvis_EVS: -0.23
rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

pHI: 0.559
hipred: Y
hipred_score: 0.655
ghis: 0.592

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.979

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mthfd2
Phenotype: liver/biliary system phenotype; embryo 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); growth/size/body region phenotype;

Gene ontology

Biological process: tetrahydrofolate interconversion;tetrahydrofolate metabolic process;folic acid metabolic process;oxidation-reduction process
Cellular component: extracellular space;mitochondrion;mitochondrial matrix
Molecular function: magnesium ion binding;methenyltetrahydrofolate cyclohydrolase activity;methylenetetrahydrofolate dehydrogenase (NAD+) activity;methylenetetrahydrofolate dehydrogenase (NADP+) activity;phosphate ion binding