MTHFD2L

methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like

Basic information

Region (hg38): 4:74114173-74303099

Links

ENSG00000163738 ∙ NCBI:441024 ∙ OMIM:614047 ∙ HGNC:31865 ∙ Uniprot:Q9H903 ∙ 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 MTHFD2L gene.

• Inborn genetic diseases (17 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTHFD2L 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						0
missense			16	1		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	1	0

Variants in MTHFD2L

This is a list of pathogenic ClinVar variants found in the MTHFD2L region.

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

Position	Type	Phenotype	Significance	ClinVar
4-74158250-G-C		not specified	Uncertain significance (Jul 25, 2023)
4-74158254-T-A		not specified	Uncertain significance (May 05, 2023)
4-74158259-G-A		not specified	Uncertain significance (Jun 29, 2022)
4-74158260-G-C		not specified	Uncertain significance (Apr 27, 2022)
4-74174525-T-C		not specified	Uncertain significance (Feb 21, 2024)
4-74174529-G-T		not specified	Uncertain significance (Feb 21, 2024)
4-74174687-G-A		not specified	Uncertain significance (Oct 18, 2021)
4-74175298-A-G		not specified	Uncertain significance (Feb 22, 2023)
4-74175356-A-T		not specified	Uncertain significance (Sep 27, 2021)
4-74175370-G-A		not specified	Uncertain significance (Jan 09, 2024)
4-74175379-A-T		not specified	Uncertain significance (May 23, 2023)
4-74199820-A-C		not specified	Uncertain significance (Feb 28, 2024)
4-74199824-G-A			not provided (-)
4-74199866-A-G		not specified	Uncertain significance (Mar 29, 2023)
4-74199892-C-T		not specified	Uncertain significance (Feb 12, 2024)
4-74199936-A-G		not specified	Uncertain significance (Nov 15, 2023)
4-74201263-G-T		not specified	Uncertain significance (Jun 02, 2023)
4-74201268-C-G		not specified	Likely benign (Aug 02, 2021)
4-74201287-T-G		not specified	Uncertain significance (Aug 02, 2022)
4-74201289-G-A		not specified	Uncertain significance (Dec 28, 2022)
4-74201320-T-C		not specified	Uncertain significance (Jun 29, 2023)
4-74201334-C-G		not specified	Uncertain significance (Jan 04, 2022)
4-74201347-A-C		not specified	Uncertain significance (Jun 29, 2022)
4-74225340-A-G		not specified	Uncertain significance (May 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTHFD2L	protein_coding	protein_coding	ENST00000395759	8	188926

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000686	0.733	125670	0	64	125734	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.169	189	183	1.04	0.00000892	2221
Missense in Polyphen		73	80.373	0.90827		970
Synonymous	-0.837	72	63.5	1.13	0.00000338	701
Loss of Function	1.13	10	14.7	0.681	7.83e-7	186

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00249	0.00226
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.0000547	0.0000544
South Asian	0.000231	0.000229
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Pathway: One carbon pool by folate - Homo sapiens (human);Trans-sulfuration and one carbon metabolism;Metabolism;folate transformations I;Metabolism of folate and pterines;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.753
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.489
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.106

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mthfd2l
• 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: histidine biosynthetic process;purine nucleotide biosynthetic process;methionine biosynthetic process;10-formyltetrahydrofolate metabolic process;tetrahydrofolate interconversion;tetrahydrofolate metabolic process;folic acid metabolic process;oxidation-reduction process
• Cellular component: mitochondrial inner membrane;mitochondrial matrix
• Molecular function: methenyltetrahydrofolate cyclohydrolase activity;methylenetetrahydrofolate dehydrogenase (NAD+) activity;methylenetetrahydrofolate dehydrogenase (NADP+) activity