AtlasGene
MTRR
5-methyltetrahydrofolate-homocysteine methyltransferase reductase
- HGNC 7473↗(opens in a new tab)
- Ensembl gene ENSG00000124275↗(opens in a new tab)
- NCBI Gene 4552↗(opens in a new tab)
Summary
- Cytogenetic location
- 5p15.31
- Coordinates
- Chromosome 5: 7,869,148–7,901,113 (GRCh38)
- Exons
- 15 exons across 32 kb
- Protein
- 698 amino acids, 77.7 kDa
- Also known as
- cblE
- MANE Select transcript
- ENST00000440940.7NM_002454.3
- Locus type
- Protein-coding
- Very high
- Confident
- Low
- Very low
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Homocystinuria & Cobalamin Disorders
- HomocystinuriaAutosomal recessive
Includes classic homocystinuria due to CBS deficiency, severe MTHFR deficiency and the combined and remethylation cobalamin disorders, which can cause lens dislocation, blood clots, skeletal changes, anaemia and developmental problems.
- ClinGen rates the link definitive
- 5 GenCC submitters rate it definitive or strong
▶Actionability
Knowing allows treatment with vitamin B6, B12, folate, betaine and diet as appropriate, which can prevent lens dislocation, thrombosis and other complications.
- Inborn Disorders of Cobalamin Metabolism and TransportAutosomal recessive
Includes defects in vitamin B12 absorption and transport such as Imerslund-Gräsbeck syndrome (CUBN, AMN), intrinsic factor deficiency (CBLIF) and transcobalamin II deficiency (TCN2), as well as intracellular cobalamin processing defects, which can cause megaloblastic anaemia, nerve damage and failure to thrive.
- ClinGen rates the link definitive
- 5 GenCC submitters rate it definitive or strong
▶Actionability
Knowing allows lifelong vitamin B12 injections or other cobalamin treatment, which can prevent anaemia and neurological damage.
How MTRR is laid out
- Coding sequence
- Untranslated region
- Intron
- Direction of transcription
- Known disease-causing sites
- Stretches short reads find hard
Exons of the gene's MANE Select transcript (release v1.5), from NCBI and EMBL-EBI, on the GRCh38 reference genome.
Chromosome bands from UCSC's GRCh38 ideogram (2022-10-29).
Nearby genes from Ensembl release 116, on GRCh38.
Exons make up 3.2 kb of the gene's 32 kb; 2,097 of those bases code for the protein.
Sequencing MTRR
3Easy
How hard MTRR is to sequence with short reads, out of 100
0 · Easy100 · Hard
Almost all of MTRR's exons sit where short reads map cleanly.
What adds to it: the share of MTRR's exons in each kind of hard region
- MappabilityStretches where 100 or 250 bp reads cannot be placed uniquely, so a call there may be missing or wrong. On its own, a gene wholly in this kind of region would score 100.0%
- HomologySegmental duplications: copies elsewhere in the genome, such as paralogues and pseudogenes, at 90% identity or more. On its own, a gene wholly in this kind of region would score 60.0%
- Shared with chrYThe pseudoautosomal regions and the X-transposed region, where chrX and chrY carry the same or nearly the same sequence, so a read from one may be placed on the other. On its own, a gene wholly in this kind of region would score 60.0%
- Reference coverageGaps in the reference assembly nearby, where there is no sequence for reads to align to. On its own, a gene wholly in this kind of region would score 50.0%
- RepeatsTandem repeats and runs of one base, which reads slip on and may not span. On its own, a gene wholly in this kind of region would score 30.2.3%
- GC contentWindows under 25% or over 65% G and C, which library preparation covers thinly. On its own, a gene wholly in this kind of region would score 20.13%
A Dante Labs score from our own research, built on NIST's Genome in a Bottle maps of hard-to-sequence regions.How it's scoredEach bar is the share of MTRR's exon bases in that kind of difficult region. Any one kind can make a gene hard on its own, and each further kind adds less: 0 when no base is in any, 100 when every base is where reads cannot be placed uniquely.
145
positions in MTRR where ClinVar classes a change as pathogenic or likely pathogenic
None of them falls in a region short reads find hard.
A whole genome covers all 32 kb of MTRR, introns included, not only the 3.2 kb of exons.
ClinVar pathogenic variants (158)
The MTRR variants ClinVar classifies pathogenic or likely pathogenic for any condition, reviewed by at least one submitter with criteria, and the most reviewed of them. It is ClinVar's public record of the gene, never a result.
- Pathogenic 63
- Pathogenic/likely pathogenic 15
- Likely pathogenic 80
| Variant | Conditions | ClinVar classification | Review status |
|---|---|---|---|
| NM_002454.3(MTRR):c.340C>T (p.Arg114Ter) | homocystinuria without methylmalonic aciduria and 2 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.763C>T (p.Gln255Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.766G>T (p.Glu256Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.903+469T>C | methylcobalamin deficiency type cblE and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1573C>T (p.Arg525Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1674dup (p.Arg559Ter) | methylcobalamin deficiency type cblE | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1678_1681del (p.Glu560Asnfs) | methylcobalamin deficiency type cblE and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1677-1G>A | methylcobalamin deficiency type cblE and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.230del (p.Gln77fs) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.270del (p.Tyr91fs) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.734del (p.Leu245fs) | methylcobalamin deficiency type cblE | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.740del (p.Pro247fs) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.741del (p.Glu248fs) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1129C>T (p.Arg377Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1156C>T (p.Arg386Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1183_1184del (p.Ser395fs) | methylcobalamin deficiency type cblE | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1252C>T (p.Arg418Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1361C>T (p.Ser454Leu) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1418_1419del (p.Val473fs) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1475G>A (p.Trp492Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1554_1557+3del | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1769+1G>A | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.1780A>T (p.Arg594Ter) | methylcobalamin deficiency type cblE and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.118G>T (p.Glu40Ter) | methylcobalamin deficiency type cblE and 1 other | Likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_002454.3(MTRR):c.166G>A (p.Val56Met) | methylcobalamin deficiency type cblE and 1 other | Likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
See all 158 with every other MTRR variant in ClinVar → (opens in a new tab)
Genes linked to the same conditions
- ABCD4ATP binding cassette subfamily D member 4Shares 2 conditions
- HCFC1host cell factor C1Shares 2 conditions
- LMBRD1LMBR1 domain containing 1Shares 2 conditions
- MMACHCmetabolism of cobalamin associated CShares 2 conditions
- MMADHCmetabolism of cobalamin associated DShares 2 conditions
- MTR5-methyltetrahydrofolate-homocysteine methyltransferaseShares 2 conditions
- PRDX1peroxiredoxin 1Shares 2 conditions
- AMNamnion associated transmembrane proteinShares 1 condition
- CBLIFcobalamin binding intrinsic factorShares 1 condition
- CBScystathionine beta-synthaseShares 1 condition
- CD320CD320 moleculeShares 1 condition
- CUBNcubilinShares 1 condition
Traits linked to MTRR
The Human Phenotype Ontology lists these as features of the rare conditions MTRR can cause. Each trait's page lists the other genes linked to it.
Abnormality of the nervous system
- Global developmental delay
- Abnormal cerebral white matter morphology
- Abnormal speech pattern
- Abnormality of movement
- Brain degeneration
- Decrease in size of the outer layer of the brain due to loss of brain cells
- Drowsiness
- Epilepsy
Show 16 more traits
- Hyperactive movements
- Intellectual disability
- Loss of consciousness
- Severe global developmental delay
- Behavioral abnormality
- Delayed myelination
- Excessive daytime sleepiness
- Lethargy
- Peripheral neuropathy
- Small brainstem
- Too much cerebrospinal fluid in the brain
- Ventriculomegaly
- Widened subarachnoid space
- Abnormal gait
- Degeneration of cerebrum
- Spinal dysraphism
Abnormality of blood and blood-forming tissues
- Megaloblastic anemia
- Normocytic anemia
- Megaloblastic bone marrow
- Increased mean corpuscular volume
- Macrocytic anemia
- Blood clot in a deep vein
- Low blood cell count
- Low blood neutrophil count
Show 1 more trait
External links
Gene records
Transcript
Protein
Where this comes from
- HGNC: the gene's symbol, name, other symbols and location.
- MANE Select v1.5, from NCBI and EMBL-EBI: the transcript, its exons and coding sequence.
- GenCC and ClinGen, released 2026-10-21: which conditions the gene is linked to, and how strongly.
- The ACMG secondary findings list, SF v3.2.
- ClinVar and the GIAB stratifications: known disease-causing sites, and the regions short reads find hard.
- The Genome in a Bottle genome stratifications, from NIST: the sequencing difficulty score.
- The Human Phenotype Ontology, release 2026-09-01: the traits linked to the gene. Find out more at hpo.jax.org.
- Data release 2026.10.21-c791e85a.
Cite this page
Dante Labs. (n.d.). MTRR gene: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase. Retrieved 22 October 2026, from https://dantelabs.com/genes/mtrr
Dante Labs. MTRR gene: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [Internet]. [cited 22 October 2026]. Available from: https://dantelabs.com/genes/mtrr
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