MTHFD1L

methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like

Basic information

Region (hg38): 6:150865678-151101887

Previous symbols: [ "FTHFSDC1" ]

Links

ENSG00000120254 ∙ NCBI:25902 ∙ OMIM:611427 ∙ HGNC:21055 ∙ Uniprot:Q6UB35 ∙ 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 MTHFD1L gene.

• Inborn genetic diseases (37 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTHFD1L 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					1	1
missense			37			37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	37	0	1

Variants in MTHFD1L

This is a list of pathogenic ClinVar variants found in the MTHFD1L region.

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

Position	Type	Phenotype	Significance	ClinVar
6-150865827-G-A		not specified	Uncertain significance (Jun 23, 2021)
6-150865832-C-A		not specified	Uncertain significance (Jun 21, 2023)
6-150865871-C-G		not specified	Uncertain significance (Sep 22, 2023)
6-150865883-C-T		not specified	Uncertain significance (Jun 16, 2023)
6-150865905-C-G		not specified	Uncertain significance (Dec 08, 2023)
6-150865925-G-A		not specified	Uncertain significance (Dec 02, 2021)
6-150865943-G-A		not specified	Uncertain significance (Nov 09, 2022)
6-150865950-G-C		not specified	Uncertain significance (Jun 05, 2023)
6-150866025-C-T		not specified	Uncertain significance (Feb 17, 2023)
6-150876115-G-A		not specified	Uncertain significance (Nov 10, 2023)
6-150876155-C-T		not specified	Uncertain significance (Jan 18, 2023)
6-150877792-A-G		not specified	Uncertain significance (Mar 12, 2024)
6-150887842-T-C		not specified	Uncertain significance (Jan 23, 2024)
6-150887857-A-G		not specified	Uncertain significance (Jan 23, 2024)
6-150887916-C-G		not specified	Uncertain significance (Feb 05, 2024)
6-150887965-G-A		not specified	Uncertain significance (Nov 07, 2022)
6-150887969-G-T		not specified	Uncertain significance (Feb 15, 2023)
6-150905665-A-G		not specified	Uncertain significance (Dec 02, 2022)
6-150905715-A-G		not specified	Uncertain significance (Aug 17, 2021)
6-150918645-C-G		not specified	Uncertain significance (Jun 03, 2022)
6-150918661-G-A		not specified	Uncertain significance (Jun 11, 2021)
6-150922247-C-G		not specified	Uncertain significance (Jan 22, 2024)
6-150926146-A-C		not specified	Uncertain significance (Sep 01, 2021)
6-150926208-T-C		not specified	Uncertain significance (Sep 01, 2021)
6-150926243-G-A		not specified	Uncertain significance (Dec 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTHFD1L	protein_coding	protein_coding	ENST00000367321	27	236339

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.94e-12	1.00	125666	0	82	125748	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.992	459	523	0.878	0.0000294	6309
Missense in Polyphen		162	217.99	0.74316		2388
Synonymous	-0.226	208	204	1.02	0.0000128	1982
Loss of Function	3.17	28	52.9	0.529	0.00000285	618

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000363	0.000363
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000425	0.000422
Middle Eastern	0.000490	0.000489
South Asian	0.000432	0.000425
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2. {ECO:0000250, ECO:0000269|PubMed:16171773}.
• Pathway: One carbon pool by folate - Homo sapiens (human);Folate malabsorption, hereditary;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;folate polyglutamylation;Folate metabolism;Metabolism;folate transformations I;Metabolism of folate and pterines;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Vitamin B9 (folate) metabolism (Consensus)

Recessive Scores

• pRec: 0.261

Intolerance Scores

• loftool: 0.815
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.54

Haploinsufficiency Scores

• pHI: 0.0847
• hipred: Y
• hipred_score: 0.706
• ghis: 0.547

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.900

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mthfd1l
• Phenotype: 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); embryo phenotype; growth/size/body region 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); craniofacial phenotype

Gene ontology

• Biological process: neural tube closure;folic acid-containing compound metabolic process;purine nucleobase biosynthetic process;10-formyltetrahydrofolate biosynthetic process;formate metabolic process;tetrahydrofolate interconversion;folic acid metabolic process;embryonic neurocranium morphogenesis;embryonic viscerocranium morphogenesis;oxidation-reduction process
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;membrane
• Molecular function: formate-tetrahydrofolate ligase activity;methylenetetrahydrofolate dehydrogenase (NADP+) activity;ATP binding;protein homodimerization activity