MTRR

Chr 5

5-methyltetrahydrofolate-homocysteine methyltransferase reductase

Also known as: MSR, cblE

NCBI Gene: 4552ENSG00000124275UniProt: Q9UBK8

This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHomocystinuria-megaloblastic anemia, cblE type
UniProtNeural tube defects, folate-sensitive

Clinical highlights

Gene-disease validity (ClinGen)
methylcobalamin deficiency type cblE · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
66
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.98
LOEUF
LOF
Mechanism· G2P
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GeneReview available — MTRR
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.71 (0.52–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.67Z-score
OE missense 1.10 (1.01–1.19)
423 obs / 386.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.71 (0.52–0.98)
0≤0.351.4
Missense OE?1.10 (1.01–1.19)
0≤0.61.4
Synonymous OE?1.14
0≤1.21.6
LoF obs/exp: 27 / 37.9Missense obs/exp: 423 / 386.2Syn Z: -1.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients