Neural tube defects, folate-sensitive: genes and variants

Genes linked to Neural tube defects, folate-sensitive

• MTHFR: Methylenetetrahydrofolate reductase (NADPH)

  It generates 5-methyltetrahydrofolate for remethylation of homocysteine to methionine, linking folate metabolism with methyl-group supply. Severe biallelic deficiency causes homocystinuria with neurologic and thrombotic complications, while common variants produce much smaller effects on homocysteine.

  19 disease-causing and 15 uncertain variants in MTHFR are linked to Neural tube defects, folate-sensitive.

Known disease-causing variants in Neural tube defects, folate-sensitive

Which prediction tools work for Neural tube defects, folate-sensitive

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• REVEL: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 86 out of 100
• PolyPhen-2: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 81 out of 100
• phyloP: 73 out of 100

Same protein, different disease

• Homocystinuria due to methylene tetrahydrofolate reductase deficiency is also caused by MTHFR variants; they fall mostly in different places as the Neural tube defects, folate-sensitive variants (43 disease-causing).

Diseases related to Neural tube defects, folate-sensitive

• Homocystinuria due to methylene tetrahydrofolate reductase deficiency, also linked to MTHFR
• Thrombophilia due to thrombin defect, also linked to MTHFR
• Schizophrenia, also linked to MTHFR

Frequently asked questions

Which genes are linked to Neural tube defects, folate-sensitive?

In CATVariant, Neural tube defects, folate-sensitive is linked to 1 analyzed protein: MTHFR (Methylenetetrahydrofolate reductase (NADPH)).

How many genetic variants are linked to Neural tube defects, folate-sensitive?

59 variants: 19 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 15 are of uncertain significance or have conflicting reports.

Which uncertain variants in Neural tube defects, folate-sensitive look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Neural tube defects, folate-sensitive?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.85, based on 18 disease-causing and 14 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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