MTRR

Chr 5p15.31

5-methyltetrahydrofolate-homocysteine methyltransferase reductase

Aliases:: cblE
MANE:: ENST00000440940.7

OMIM: 602568 ↗NCBI: 4552 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

MTRR · Q9UBK8

v62025-08-01

Predicted Aligned Error matrix for MTRR — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

85.3/ 100

Confident

698 residues

Confidence breakdown

Very high(≥ 90)71%
Confident(70–90)14%
Low(50–70)5%
Very low(< 50)11%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Cytopenias and congenital anaemias
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Rare anaemia
BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
Familial Meniere Disease

+5 more panels — install the extension to see the full list inline on any page.

Disease associations (Open Targets)

methylcobalamin deficiency type cblE
0.83
neural tube defects, folate-sensitive
0.67
homocystinuria without methylmalonic aciduria
0.50
hereditary disease
0.49
methylmalonic aciduria and homocystinuria type cblG
0.46
isolated spina bifida
0.37
neurodegenerative disease
0.37
methylmalonic aciduria and homocystinuria type cblE
0.37
alcohol drinking
0.30
urolithiasis
0.29

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Methionine synthase reductase

Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species (Probable). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme (PubMed:16769880). Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (PubMed:16769880)