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MTHFRD
MCID: HMC041
MIFTS: 48

Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity (MTHFRD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes
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Aliases & Classifications for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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MalaCards integrated aliases for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

Name: Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity 57 70
Methylenetetrahydrofolate Reductase Deficiency 57 73 72 54 70
Homocystinuria Due to Mthfr Deficiency 57 20 29 13 6
Homocystinuria Due to Methylene Tetrahydrofolate Reductase Deficiency 58 29 6
Mthfr Deficiency 57 73 58
Homocysteinemia Due to Methylenetetrahydro-Folate Reductase Deficiency 20
Homocysteinuria Due to Methylenetetrahydro-Folate Reductase Deficiency 20
5,10 Alpha Methylenetetrahydro-Folate Reductase Deficiency 20
5,10-Alpha-Methylenetetrahydro-Folate Reductase Deficiency 20
5,10-Methylenetetrahydrofolate Reductase Deficiency 70
Methylenetetrahydro-Folate Reductase Deficiency 20
Methylene Tetrahydrofolate Reductase Deficiency 58
Mthfrd 72

Characteristics:

Orphanet epidemiological data:

58
homocystinuria due to methylene tetrahydrofolate reductase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
two thirds of patients are female
clinical severity varies
age of onset ranges from neonate to adulthood


HPO:

31
homocystinuria due to deficiency of n -methylenetetrahydrofolate reductase activity:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Sources

Summaries for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

About this section
GARD : 20 Homocystinuria due to MTHFR deficiency is a genetic condition that results from poor metabolism of folate (also called vitamin B9), due to a lack of working enzyme called MTHFR. The gene that tells our body how to make the enzyme is also called MTHFR. At least 40 rare MTHFR gene variants have been found in people with decreased or no working enzyme. Very common gene variants (C677T and A1298C) can cause some decrease in enzyme function. People with homocystinuria due to MTHFR deficiency tend to have two rare variants or sometimes a rare variant and a common variant. Very rarely people inherit a combination of three or four common variants from their parents (for example two C677T variants and two A1298C variants) and may also develop very high levels of homocystine in their body. Homocystinuria usually does not show symptoms in a newborn baby. If untreated, children show signs and symptoms of severe homocystinuria in infancy. Newborn screening in most states includes a screening test for homocystinuria so that newborn infants can be treated early in their lives. However, homocystinuria due to MTHFR variants can be milder, presenting in later childhood or in adulthood. Symptoms may include abnormal clotting, developmental delay, seizures, intellectual disability, and microcephaly. Severe homocystinuria can also be caused by gene variants in other genes besides MTHFR. For more information about other causes of homocystinuria, see the GARD page: https://rarediseases.info.nih.gov/diseases/10770/homocystinuria For more information on having two common MTHFR gene variants (specifically, C677T and A1298C) visit our page: MTHFR gene variant

MalaCards based summary : Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity, also known as methylenetetrahydrofolate reductase deficiency, is related to homocysteinemia and homocystinuria, and has symptoms including seizures, muscle weakness and muscle spasticity. An important gene associated with Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity is MTHFR (Methylenetetrahydrofolate Reductase), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Selenium Micronutrient Network. Affiliated tissues include brain, placenta and eye, and related phenotypes are gait disturbance and abnormal enzyme/coenzyme activity

OMIM® : 57 Methylenetetrahydrofolate reductase deficiency is a common inborn error of folate metabolism. The phenotypic spectrum ranges from severe neurologic deterioration and early death to asymptomatic adults. In the classic form, both thermostable and thermolabile enzyme variants have been identified (Rosenblatt et al., 1992). (236250) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Methylenetetrahydrofolate reductase deficiency: Autosomal recessive disorder with a wide range of features including homocysteinuria, homocysteinemia [MIM:603174], developmental delay, severe mental retardation, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders.

Wikipedia : 73 Methylenetetrahydrofolate reductase deficiency is the most common genetic cause of elevated serum levels... more...

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Related Diseases for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Diseases related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 106)
# Related Disease Score Top Affiliating Genes
1 homocysteinemia 31.7 MTR MTHFR
2 homocystinuria 30.9 MTR MTHFR
3 neural tube defects 30.0 MTR MTHFR
4 megaloblastic anemia 29.9 MTR MTHFR
5 methylmalonic acidemia 29.7 MTR MTHFR
6 vascular disease 29.5 MTR MTHFR
7 cardiovascular system disease 29.1 MTR MTHFR
8 folate malabsorption, hereditary 11.2
9 mthfr gene variant 11.0
10 paraplegia 10.4
11 autosomal recessive disease 10.3
12 polyneuropathy 10.3
13 hypotonia 10.3
14 stroke, ischemic 10.2
15 microcephaly 10.2
16 hydrocephalus 10.2
17 neuropathy 10.2
18 peripheral vascular disease 10.2
19 retinal vein occlusion 10.2
20 constipation 10.2
21 ocular motor apraxia 10.1
22 ataxia and polyneuropathy, adult-onset 10.1
23 thrombosis 10.1
24 non-alcoholic fatty liver disease 10.1
25 isolated ectopia lentis 10.1
26 epilepsy 10.1
27 arteriosclerosis 10.1
28 hereditary spastic paraplegia 10.1
29 peripheral nervous system disease 10.1
30 placenta disease 10.1
31 spastic paraparesis 10.1
32 encephalopathy 10.1
33 angelman syndrome 10.0
34 hypertriglyceridemia, familial 10.0
35 schizophrenia 10.0
36 epilepsy, myoclonic juvenile 10.0
37 myoclonic epilepsy of unverricht and lundborg 10.0
38 scoliosis 10.0
39 leukodystrophy 10.0
40 placenta praevia 10.0
41 heart disease 10.0
42 communicating hydrocephalus 10.0
43 focal epilepsy 10.0
44 thrombophilia 10.0
45 early myoclonic encephalopathy 10.0
46 central nervous system disease 10.0
47 thrombophlebitis 10.0
48 myopathy 10.0
49 demyelinating polyneuropathy 10.0
50 adenoma 10.0

Graphical network of the top 20 diseases related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:



Diseases related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity
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Symptoms & Phenotypes for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Human phenotypes related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

58 31 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
2 abnormal enzyme/coenzyme activity 58 31 hallmark (90%) Very frequent (99-80%) HP:0012379
3 lower limb muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0007340
4 hyperhomocystinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002160
5 cystathioninemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003286
6 homocystinuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0002156
7 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
8 mental deterioration 58 31 frequent (33%) Frequent (79-30%) HP:0001268
9 peripheral neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0009830
10 spastic paraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0002313
11 brain imaging abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0410263
12 abnormality of the periventricular white matter 58 31 frequent (33%) Frequent (79-30%) HP:0002518
13 psychotic episodes 58 31 frequent (33%) Frequent (79-30%) HP:0000725
14 hypomethioninemia 58 31 frequent (33%) Frequent (79-30%) HP:0003658
15 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
16 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
17 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
18 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
19 specific learning disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001328
20 apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002104
21 headache 58 31 occasional (7.5%) Occasional (29-5%) HP:0002315
22 lethargy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001254
23 hemiparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001269
24 generalized neonatal hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008935
25 focal-onset seizure 58 31 occasional (7.5%) Occasional (29-5%) HP:0007359
26 brain atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0012444
27 deep venous thrombosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002625
28 thromboembolic stroke 58 31 occasional (7.5%) Occasional (29-5%) HP:0001727
29 atrophy of the spinal cord 58 31 occasional (7.5%) Occasional (29-5%) HP:0006827
30 psychotic mentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001345
31 bilateral tonic-clonic seizure 31 occasional (7.5%) HP:0002069
32 nystagmus 58 31 very rare (1%) Very rare (<4-1%) HP:0000639
33 hydrocephalus 58 31 very rare (1%) Very rare (<4-1%) HP:0000238
34 microcephaly 58 31 very rare (1%) Very rare (<4-1%) HP:0000252
35 optic atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0000648
36 ventriculomegaly 58 31 very rare (1%) Very rare (<4-1%) HP:0002119
37 stroke 58 31 very rare (1%) Very rare (<4-1%) HP:0001297
38 encephalopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0001298
39 generalized myoclonic seizure 31 very rare (1%) HP:0002123
40 generalized non-motor (absence) seizure 31 very rare (1%) HP:0002121
41 behavioral abnormality 58 31 Very frequent (99-80%) HP:0000708
42 seizures 58 Frequent (79-30%)
43 muscle weakness 31 HP:0001324
44 cognitive impairment 58 Occasional (29-5%)
45 generalized myoclonic seizures 58 Very rare (<4-1%)
46 abnormality of the eye 58 Very rare (<4-1%)
47 paresthesia 31 HP:0003401
48 psychosis 58 Occasional (29-5%)
49 upper motor neuron dysfunction 58 Very frequent (99-80%)
50 generalized tonic-clonic seizures 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
stroke
incoordination
developmental delay
paresthesias
more
Head And Neck Head:
microcephaly

Muscle Soft Tissue:
muscle weakness

Laboratory Abnormalities:
homocystinuria
methylenetetrahydrofolate reductase deficiency
low to normal plasma methionine
homocystinemia

Clinical features from OMIM®:

236250 (Updated 20-May-2021)

UMLS symptoms related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:


seizures; muscle weakness; muscle spasticity

GenomeRNAi Phenotypes related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance GR00327-A 8.62 MTHFR MTR
Sources

Drugs & Therapeutics for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Investigation the Incidence of Methylenetetrahydrofolate Reductase Deficiency in Ischemic Cerebrovascular Diseases Presenting With Epileptic Seizures in Adults Completed NCT04287881

Search NIH Clinical Center for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity

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Genetic Tests for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Genetic tests related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

# Genetic test Affiliating Genes
1 Homocystinuria Due to Methylene Tetrahydrofolate Reductase Deficiency 29 MTHFR
2 Homocystinuria Due to Mthfr Deficiency 29
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Anatomical Context for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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MalaCards organs/tissues related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

40
Brain, Placenta, Eye, Spinal Cord, Liver, Spleen, Heart
Sources

Publications for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Articles related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

(show top 50) (show all 176)
# Title Authors PMID Year
1
Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. 54 61 57 6
7726158 1995
2
Pearls & oy-sters: familial epileptic encephalopathy due to methylenetetrahydrofolate reductase deficiency. 57 6 61
25024447 2014
3
Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency. 61 57 6
17409006 2007
4
Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. 57 6 61
3347350 1988
5
Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. 61 57 6
6381059 1984
6
The thermolabile variant 677C-->T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. 57 6
10923034 2000
7
Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. 6 57
9133512 1997
8
Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. 57 6
8940272 1996
9
A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. 6 57
7647779 1995
10
Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. 57 6
7920641 1994
11
Relations between molecular and biological abnormalities in 11 families from siblings affected with methylenetetrahydrofolate reductase deficiency. 54 6 61
12733064 2003
12
Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation. 54 6 61
12673793 2003
13
Methylenetetrahydrofolate reductase deficiency in four siblings: a clinical, biochemical, and molecular study of the family. 61 54 6
10767000 2000
14
Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. 61 54 6
9781030 1998
15
Molecular genetics of methylenetetrahydrofolate reductase deficiency. 61 57 54
8892013 1996
16
Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers. 57 54 61
8456826 1993
17
Functional characterization of missense mutations in severe methylenetetrahydrofolate reductase deficiency using a human expression system. 61 6
27743313 2017
18
Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report. 61 6
28241805 2017
19
Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency. 6 61
26872964 2016
20
Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening. 6 61
25856670 2016
21
Treatment with Mefolinate (5-Methyltetrahydrofolate), but Not Folic Acid or Folinic Acid, Leads to Measurable 5-Methyltetrahydrofolate in Cerebrospinal Fluid in Methylenetetrahydrofolate Reductase Deficiency. 6 61
26898294 2016
22
Insights into severe 5,10-methylenetetrahydrofolate reductase deficiency: molecular genetic and enzymatic characterization of 76 patients. 6 61
25736335 2015
23
Severe 5,10-methylenetetrahydrofolate reductase deficiency and two MTHFR variants in an adolescent with progressive myoclonic epilepsy. 61 6
25079578 2014
24
Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia. 61 6
24797679 2014
25
Acute leukoencephalopathy possibly induced by phenytoin intoxication in an adult patient with methylenetetrahydrofolate reductase deficiency. 61 6
21480888 2011
26
5,10-Methylenetetrahydrofolate reductase deficiency with progressive polyneuropathy in an infant. 61 6
20850942 2011
27
Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. 61 6
12840091 2003
28
Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency revealed by stroke in adult siblings. 61 57
1866027 1991
29
Prenatal diagnosis of 5,10-methylenetetrahydrofolate reductase deficiency. 61 57
3889647 1985
30
5,10-Methylenetetrahydrofolate reductase deficiency. Clinical and biochemical features of a further case. 57 61
3939530 1985
31
Prenatal diagnosis for methylenetetrahydrofolate reductase deficiency. 57 61
6406655 1983
32
Homocystinuria caused by 5,10-methylenetetrahydrofolate reductase deficiency: a case in an infant responding to methionine, folinic acid, pyridoxine, and vitamin B12 therapy. 57 61
7007598 1981
33
Methylenetetrahydrofolate reductase in cultured human cells. II. Genetic and biochemical studies of methylenetetrahydrofolate reductase deficiency. 57 61
917613 1977
34
Detection of homozygotes and heterozygotes with methylenetetrahydrofolate reductase deficiency. 61 57
886213 1977
35
Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency. 57 61
1272636 1976
36
Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency. 6
26025547 2016
37
Reversal of respiratory failure in both neonatal and late onset isolated remethylation disorders. 6
24997712 2014
38
Oxidative stress and apoptosis in homocystinuria patients with genetic remethylation defects. 6
22887477 2013
39
Methylenetetrahydrofolate reductase (MTHFR) deficiency and infantile epilepsy. 6
21778025 2011
40
Isolated remethylation disorders: do our treatments benefit patients? 6
20490923 2011
41
Life-threatening methylenetetrahydrofolate reductase (MTHFR) deficiency with extremely early onset: characterization of two novel mutations in compound heterozygous patients. 6
20356773 2010
42
Mutations in cystathionine beta-synthase or methylenetetrahydrofolate reductase gene increase N-homocysteinylated protein levels in humans. 57
18708589 2008
43
The methylenetetrahydrofolate reductase 677C-->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. 6
17436239 2007
44
In genetic control of disease, does 'race' matter? 6
15565101 2004
45
Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity. 6
15048559 2004
46
Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis. 6
12560871 2003
47
Implications on human fertility of the 677C-->T and 1298A-->C polymorphisms of the MTHFR gene: consequences of a possible genetic selection. 6
12356947 2002
48
Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis. 6
12196644 2002
49
A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. 6
11929966 2002
50
The frequent 5,10-methylenetetrahydrofolate reductase C677T polymorphism is associated with a common haplotype in whites, Japanese, and Africans. 6
11781870 2002
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Variations for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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ClinVar genetic disease variations for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

6 (show top 50) (show all 208)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MTHFR NM_005957.4(MTHFR):c.470G>A (p.Arg157Gln) SNV Pathogenic 3519 rs121434295 GRCh37: 1:11861223-11861223
GRCh38: 1:11801166-11801166
2 MTHFR NM_005957.4(MTHFR):c.971A>G (p.Asn324Ser) SNV Pathogenic 3522 rs267606887 GRCh37: 1:11855215-11855215
GRCh38: 1:11795158-11795158
3 MTHFR NM_005957.4(MTHFR):c.1015T>G (p.Trp339Gly) SNV Pathogenic 3523 rs267606886 GRCh37: 1:11855171-11855171
GRCh38: 1:11795114-11795114
4 MTHFR MTHFR, 1084C-T SNV Pathogenic 3524 GRCh37:
GRCh38:
5 MTHFR MTHFR, 1711C-T SNV Pathogenic 3525 GRCh37:
GRCh38:
6 MTHFR MTHFR, 1081C-T SNV Pathogenic 3526 GRCh37:
GRCh38:
7 MTHFR NM_005957.4(MTHFR):c.968T>C (p.Leu323Pro) SNV Pathogenic 3529 rs121434297 GRCh37: 1:11855218-11855218
GRCh38: 1:11795161-11795161
8 MTHFR NM_005957.4(MTHFR):c.547C>T (p.Arg183Ter) SNV Pathogenic 3518 rs121434294 GRCh37: 1:11860308-11860308
GRCh38: 1:11800251-11800251
9 MTHFR NM_005957.4(MTHFR):c.1743G>A (p.Met581Ile) SNV Pathogenic 3527 rs45590836 GRCh37: 1:11851273-11851273
GRCh38: 1:11791216-11791216
10 MTHFR NM_005957.4(MTHFR):c.1129C>T (p.Arg377Cys) SNV Pathogenic 3528 rs121434296 GRCh37: 1:11854823-11854823
GRCh38: 1:11794766-11794766
11 MTHFR NM_005957.4(MTHFR):c.-13-28_-13-27del Deletion Pathogenic 187865 rs1553188112 GRCh37: 1:11863213-11863214
GRCh38: 1:11803156-11803157
12 MTHFR NM_005957.4(MTHFR):c.137G>A (p.Arg46Gln) SNV Pathogenic 187867 rs776483190 GRCh37: 1:11863037-11863037
GRCh38: 1:11802980-11802980
13 MTHFR NM_005957.4(MTHFR):c.176G>C (p.Trp59Ser) SNV Pathogenic 187868 rs786204007 GRCh37: 1:11862998-11862998
GRCh38: 1:11802941-11802941
14 MTHFR NM_005957.4(MTHFR):c.202C>G (p.Arg68Gly) SNV Pathogenic 187869 rs763539350 GRCh37: 1:11862972-11862972
GRCh38: 1:11802915-11802915
15 MTHFR NM_005957.4(MTHFR):c.244C>T (p.Arg82Trp) SNV Pathogenic 187870 rs786204009 GRCh37: 1:11861449-11861449
GRCh38: 1:11801392-11801392
16 MTHFR NM_005957.4(MTHFR):c.264_302dup (p.Leu89_Pro101dup) Duplication Pathogenic 187871 rs786204010 GRCh37: 1:11861390-11861391
GRCh38: 1:11801333-11801334
17 MTHFR NM_005957.4(MTHFR):c.673A>C (p.Ile225Leu) SNV Pathogenic 187879 rs200100285 GRCh37: 1:11856370-11856370
GRCh38: 1:11796313-11796313
18 MTHFR NM_001330358.1(MTHFR):c.794_796TCA[2] (p.Ile267del) Microsatellite Pathogenic 187880 rs786204016 GRCh37: 1:11856364-11856366
GRCh38: 1:11796307-11796309
19 MTHFR NM_005957.4(MTHFR):c.760C>T (p.Pro254Ser) SNV Pathogenic 187881 rs786204017 GRCh37: 1:11856283-11856283
GRCh38: 1:11796226-11796226
20 MTHFR NM_005957.4(MTHFR):c.764G>T (p.Gly255Val) SNV Pathogenic 187882 rs786204018 GRCh37: 1:11856279-11856279
GRCh38: 1:11796222-11796222
21 MTHFR NM_005957.4(MTHFR):c.769T>G (p.Phe257Val) SNV Pathogenic 187884 rs786204019 GRCh37: 1:11856274-11856274
GRCh38: 1:11796217-11796217
22 MTHFR NM_005957.4(MTHFR):c.780+1G>T SNV Pathogenic 187885 rs786204020 GRCh37: 1:11856262-11856262
GRCh38: 1:11796205-11796205
23 MTHFR NM_005957.4(MTHFR):c.1004G>A (p.Arg335His) SNV Pathogenic 187886 rs543016186 GRCh37: 1:11855182-11855182
GRCh38: 1:11795125-11795125
24 MTHFR NM_005957.4(MTHFR):c.1042C>T (p.Pro348Ser) SNV Pathogenic 187887 rs786204021 GRCh37: 1:11854910-11854910
GRCh38: 1:11794853-11794853
25 MTHFR NM_005957.4(MTHFR):c.1060C>T (p.His354Tyr) SNV Pathogenic 187888 rs786204022 GRCh37: 1:11854892-11854892
GRCh38: 1:11794835-11794835
26 MTHFR NM_005957.4(MTHFR):c.1088G>A (p.Arg363His) SNV Pathogenic 187889 rs786204023 GRCh37: 1:11854864-11854864
GRCh38: 1:11794807-11794807
27 MTHFR NM_005957.4(MTHFR):c.1114A>G (p.Lys372Glu) SNV Pathogenic 187890 rs786204024 GRCh37: 1:11854838-11854838
GRCh38: 1:11794781-11794781
28 MTHFR NM_005957.4(MTHFR):c.1167-2del Deletion Pathogenic 187891 rs780014899 GRCh37: 1:11854597-11854597
GRCh38: 1:11794540-11794540
29 MTHFR NM_005957.4(MTHFR):c.1262G>C (p.Trp421Ser) SNV Pathogenic 187892 rs200137991 GRCh37: 1:11854500-11854500
GRCh38: 1:11794443-11794443
30 MTHFR NM_005957.4(MTHFR):c.1320G>A (p.Ser440=) SNV Pathogenic 187893 rs367585605 GRCh37: 1:11854442-11854442
GRCh38: 1:11794385-11794385
31 MTHFR NM_005957.4(MTHFR):c.1516T>G (p.Tyr506Asp) SNV Pathogenic 187894 rs786204026 GRCh37: 1:11853978-11853978
GRCh38: 1:11793921-11793921
32 MTHFR NM_005957.4(MTHFR):c.1530+2T>C SNV Pathogenic 187895 rs786204027 GRCh37: 1:11853962-11853962
GRCh38: 1:11793905-11793905
33 MTHFR NM_005957.4(MTHFR):c.1606G>T (p.Val536Phe) SNV Pathogenic 187896 rs786204028 GRCh37: 1:11852361-11852361
GRCh38: 1:11792304-11792304
34 MTHFR NM_005957.4(MTHFR):c.1632+2T>G SNV Pathogenic 187897 rs749765738 GRCh37: 1:11852333-11852333
GRCh38: 1:11792276-11792276
35 MTHFR NM_005957.4(MTHFR):c.1683G>A (p.Trp561Ter) SNV Pathogenic 187898 rs786204030 GRCh37: 1:11851333-11851333
GRCh38: 1:11791276-11791276
36 MTHFR NM_005957.4(MTHFR):c.1724T>G (p.Val575Gly) SNV Pathogenic 187899 rs786204031 GRCh37: 1:11851292-11851292
GRCh38: 1:11791235-11791235
37 MTHFR NM_005957.4(MTHFR):c.1752+1G>T SNV Pathogenic 187900 rs747846362 GRCh37: 1:11851263-11851263
GRCh38: 1:11791206-11791206
38 MTHFR NM_005957.4(MTHFR):c.1753-18G>A SNV Pathogenic 187901 rs777661576 GRCh37: 1:11850973-11850973
GRCh38: 1:11790916-11790916
39 MTHFR NM_005957.4(MTHFR):c.1793T>C (p.Leu598Pro) SNV Pathogenic 187902 rs786204034 GRCh37: 1:11850915-11850915
GRCh38: 1:11790858-11790858
40 MTHFR NM_001330358.1(MTHFR):c.1920_1921delinsGT (p.Tyr640_Glu641delinsTer) Indel Pathogenic 187903 rs786204035 GRCh37: 1:11850910-11850911
GRCh38: 1:11790853-11790854
41 MTHFR NM_005957.4(MTHFR):c.1808C>G (p.Ser603Cys) SNV Pathogenic 187904 rs758206023 GRCh37: 1:11850900-11850900
GRCh38: 1:11790843-11790843
42 MTHFR NM_005957.4(MTHFR):c.1883T>C (p.Leu628Pro) SNV Pathogenic 187905 rs786204037 GRCh37: 1:11850825-11850825
GRCh38: 1:11790768-11790768
43 MTHFR NM_005957.4(MTHFR):c.1969T>C (p.Ter657Arg) SNV Pathogenic 187906 rs768434408 GRCh37: 1:11850739-11850739
GRCh38: 1:11790682-11790682
44 MTHFR NM_005957.4(MTHFR):c.388T>C (p.Cys130Arg) SNV Pathogenic 187874 rs786204012 GRCh37: 1:11861305-11861305
GRCh38: 1:11801248-11801248
45 MTHFR NM_005957.4(MTHFR):c.440A>C (p.Gln147Pro) SNV Pathogenic 187875 rs786204013 GRCh37: 1:11861253-11861253
GRCh38: 1:11801196-11801196
46 MTHFR NM_005957.4(MTHFR):c.587G>A (p.Gly196Asp) SNV Pathogenic 187877 rs786204014 GRCh37: 1:11856456-11856456
GRCh38: 1:11796399-11796399
47 MTHFR NM_005957.4(MTHFR):c.236+1G>A SNV Pathogenic 222892 rs1057519359 GRCh37: 1:11862937-11862937
GRCh38: 1:11802880-11802880
48 MTHFR NM_005957.4(MTHFR):c.662del (p.Gly221fs) Deletion Pathogenic 222895 rs1057519362 GRCh37: 1:11856381-11856381
GRCh38: 1:11796324-11796324
49 MTHFR NM_005957.4(MTHFR):c.1033C>T (p.Arg345Cys) SNV Pathogenic 222896 rs759031330 GRCh37: 1:11854919-11854919
GRCh38: 1:11794862-11794862
50 MTHFR NM_005957.4(MTHFR):c.416C>T (p.Thr139Met) SNV Pathogenic 222893 rs1057519360 GRCh37: 1:11861277-11861277
GRCh38: 1:11801220-11801220

UniProtKB/Swiss-Prot genetic disease variations for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity:

72 (show top 50) (show all 53)
# Symbol AA change Variation ID SNP ID
1 MTHFR p.Arg52Gln VAR_004319 rs754980119
2 MTHFR p.Arg157Gln VAR_004320 rs121434295
3 MTHFR p.Thr227Met VAR_004321 rs748571395
4 MTHFR p.Pro251Leu VAR_004322
5 MTHFR p.Arg325Cys VAR_004323 rs371085894
6 MTHFR p.Arg335Cys VAR_004324 rs748289202
7 MTHFR p.Arg357Cys VAR_004325 rs779993607
8 MTHFR p.Arg51Pro VAR_009530 rs201618781
9 MTHFR p.Leu323Pro VAR_009531 rs121434297
10 MTHFR p.Asn324Ser VAR_009532 rs267606887
11 MTHFR p.Trp339Gly VAR_009533 rs267606886
12 MTHFR p.Arg377Cys VAR_009534 rs121434296
13 MTHFR p.Gly387Asp VAR_009535 rs143087249
14 MTHFR p.Pro572Leu VAR_009536 rs144508139
15 MTHFR p.Glu586Lys VAR_009537 rs983672500
16 MTHFR p.Arg46Gln VAR_074111 rs776483190
17 MTHFR p.Arg46Trp VAR_074112 rs138189536
18 MTHFR p.Trp59Ser VAR_074113 rs786204007
19 MTHFR p.Arg68Gly VAR_074114 rs763539350
20 MTHFR p.Arg82Trp VAR_074115 rs786204009
21 MTHFR p.Ala113Thr VAR_074116 rs147257424
22 MTHFR p.His127Tyr VAR_074117 rs769381688
23 MTHFR p.Thr129Asn VAR_074118
24 MTHFR p.Cys130Arg VAR_074119 rs786204012
25 MTHFR p.Gln147Pro VAR_074120 rs786204013
26 MTHFR p.Gly149Val VAR_074121
27 MTHFR p.Ile153Met VAR_074122 rs767890671
28 MTHFR p.Ala175Thr VAR_074123 rs118263598
29 MTHFR p.Arg183Gln VAR_074124 rs574132670
30 MTHFR p.Ala195Val VAR_074125 rs760161369
31 MTHFR p.Gly196Asp VAR_074126 rs786204014
32 MTHFR p.Val218Leu VAR_074128
33 MTHFR p.Ile225Leu VAR_074129 rs200100285
34 MTHFR p.Val253Phe VAR_074131
35 MTHFR p.Pro254Ser VAR_074132 rs786204017
36 MTHFR p.Gly255Val VAR_074133 rs786204018
37 MTHFR p.Ile256Asn VAR_074134 rs373398993
38 MTHFR p.Phe257Val VAR_074135 rs786204019
39 MTHFR p.Arg335His VAR_074136 rs543016186
40 MTHFR p.Met338Thr VAR_074137 rs368321176
41 MTHFR p.Pro348Ser VAR_074138 rs786204021
42 MTHFR p.His354Tyr VAR_074139 rs786204022
43 MTHFR p.Arg363His VAR_074140 rs786204023
44 MTHFR p.Lys372Glu VAR_074141 rs786204024
45 MTHFR p.Arg377His VAR_074142 rs750323424
46 MTHFR p.Trp421Ser VAR_074143 rs200137991
47 MTHFR p.Phe435Ser VAR_074144 rs754015864
48 MTHFR p.Tyr506Asp VAR_074145 rs786204026
49 MTHFR p.Val536Phe VAR_074146 rs786204028
50 MTHFR p.Val574Gly VAR_074147

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Expression for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Search GEO for disease gene expression data for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity.
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Pathways for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Pathways related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Metabolism of water-soluble vitamins and cofactors 65
Show member pathways
 11.86 MTR MTHFR
2
Selenium Micronutrient Network 1
Show member pathways
 11.49 MTR MTHFR
3
Carbon metabolism 36
Show member pathways
 11.28 MTR MTHFR
4
One carbon pool by folate 36
Show member pathways
 10.78 MTR MTHFR
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GO Terms for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

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Biological processes related to Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate Reductase Activity according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 methionine biosynthetic process GO:0009086 8.62 MTR MTHFR
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Sources for Homocystinuria Due to Deficiency of N -Methylenetetrahydrofolate...

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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