MTHFSD
protein-codingmethenyltetrahydrofolate synthetase domain containing, the group of RNA binding motif containing
Gene summary
Enables RNA binding activity. Predicted to be active in cytoplasm. [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 ~25.1 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 MTHFSD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001159377.2. 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 | 0 | |||||
| missense | 74 | 4 | 78 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 77 | 4 | 0 | 81 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001152849.1 | 8 | MANE Select | |
| Ensembl | ENSP00000354152.6 | 8 | MANE Select | |
| RefSeq | NP_001152850.1 | 8 | Standard | |
| RefSeq | NP_001152851.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- RNA binding
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360900
- Coding exons
- 8
- Length
- 25060
- Individuals with no LoFs
- 124686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 115
- Defined
- 124801
- p
- 0.000461
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.984 | 245 | 205 | 1.19 | 0.0000121 | 2405 |
| Missense (PolyPhen) | 113 | 89.597 | 1.2612 | 984 | ||
| Synonymous | -0.210 | 90 | 87.5 | 1.03 | 0.00000582 | 791 |
| Loss of Function | -0.500 | 16 | 14.0 | 1.14 | 7.43e-7 | 157 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.00058 | 0.00058 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.0013 | 0.0013 | notable |
| Other | 0.0012 | 0.0012 | notable |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0913
Intolerance Scores
- LoFtool
- 0.928
- RVIS EVS
- 1.31
- RVIS percentile EVS
- 94.02
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.833
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |