MTHFD2L
protein-codingmethylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like
Gene summary
Predicted to enable methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~188.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MTHFD2L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001144978.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 51 | 2 | 53 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 56 | 2 | 0 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001138450.1 | 8 | MANE Select | |
| Ensembl | ENSP00000321984.7 | 8 | MANE Select | |
| RefSeq | NP_001004346.2 | 7 | Standard | |
| RefSeq | NP_001338239.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- One carbon pool by folate - Homo sapiens (human)
- Trans-sulfuration and one carbon metabolism
- Metabolism
- folate transformations I
- Metabolism of folate and pterines
Biological Process
- histidine biosynthetic process
- purine nucleotide biosynthetic process
- methionine biosynthetic process
- 10-formyltetrahydrofolate metabolic process
- tetrahydrofolate interconversion
Molecular Function
- methenyltetrahydrofolate cyclohydrolase activity
- methylenetetrahydrofolate dehydrogenase (NAD+) activity
- methylenetetrahydrofolate dehydrogenase (NADP+) activity
Cellular Component
- mitochondrial inner membrane
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395759
- Coding exons
- 8
- Length
- 188926
- Individuals with no LoFs
- 125670
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 125734
- p
- 0.000255
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.169 | 189 | 183 | 1.04 | 0.00000892 | 2221 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0023 | 0.0021 | notable |
| Latino/Admixed American | 0.00017 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.753
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Indispensability pred.
- N
- Indispensability score
- 0.106
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |