MTR
Chr 1AR5-methyltetrahydrofolate-homocysteine methyltransferase
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:27771510). MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate (PubMed:16769880, PubMed:17288554, PubMed:27771510). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:16769880, PubMed:27771510)
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
1541 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 13 | 2 | 13 | 0 | 28 |
Likely Pathogenic | 11 | 0 | 3 | 0 | 14 |
VUS | 1 | 68 | 8 | 0 | 77 |
Likely Benign | 0 | 2 | 167 | 163 | 332 |
Benign | 0 | 0 | 12 | 1 | 13 |
Conflicting | — | 1 | |||
| Total | 25 | 72 | 203 | 164 | 465 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MTR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
MTR-related methylcobalamin deficiency
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
{Neural tube defects, folate-sensitive, susceptibility to}
MIM #601634Molecular basis of disorder known
Homocystinuria-megaloblastic anemia, cblG complementation type
MIM #250940Molecular basis of disorder known
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients
ACTIVE NOT RECRUITINGA Study to Investigate the Efficacy and Safety of Crizanlizumab (5 mg/kg) Compared With Placebo in Adolescent and Adult Sickle Cell Disease Patients Who Experience Frequent Vaso-Occlusive Crises (SPARKLE)
RECRUITINGMechanisms of Neurodynamic Treatments
RECRUITINGA Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)
RECRUITINGA Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
RECRUITINGClinical and Laboratory Study of Methylmalonic Acidemia
RECRUITINGExternal Resources
Links to major genomics databases and tools