MTRR

Chr 5AR

5-methyltetrahydrofolate-homocysteine methyltransferase reductase

Also known as: MSR, cblE

The protein regenerates methionine synthase to its functional state, enabling methionine synthesis and supporting folate metabolism and cellular methylation processes. Mutations cause homocystinuria-megaloblastic anemia (cbl E type) and increase susceptibility to neural tube defects through autosomal recessive inheritance. The pathogenic mechanism involves gain-of-function effects that disrupt normal methionine synthesis pathways.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.982 OMIM phenotypes
Clinical SummaryMTRR
🧬
Gene-Disease Validity (ClinGen)
methylcobalamin deficiency type cblE · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.71 (0.520.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.67Z-score
OE missense 1.10 (1.011.19)
423 obs / 386.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.520.98)
00.351.4
Missense OE1.10 (1.011.19)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 27 / 37.9Missense obs/exp: 423 / 386.2Syn Z: -1.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMTRR-related homocystinuria-megaloblastic anemia, cblE typeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6260th %ile
GOF
0.72top 25%
LOF
0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MTRR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →