Can PepFold design peptides for rs1801131?

Yes. PepFold accepts rs1801131 as input, annotates it via ClinVar, maps it to the MTHFR protein via UniProt, generates peptide candidates targeting affected functional domains, predicts their 3D structures with ESMFold, and produces a scored report with Fmoc-SPPS synthesis protocols.

SNP Database

rs1801131 — MTHFR A1298C (Glu429Ala)

Q: What gene is rs1801131 in?

rs1801131 is a variant in the MTHFR (Methylenetetrahydrofolate Reductase) gene located on chromosome 1p36.22. Catalyzes conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary circulating form of folate. Essential for homocysteine remethylation and one-carbon metabolism.

Q: What is the clinical significance of rs1801131?

rs1801131 is classified as "Drug response" in ClinVar. The Glu429Ala substitution is in the S-adenosylmethionine regulatory domain of MTHFR. It reduces allosteric regulation rather than catalytic activity directly, making the enzyme less responsive to SAM feedback inhibition.

Drug response · ~30% global (C allele)

rs1801131 is the second most studied MTHFR variant. The A1298C substitution reduces enzyme activity by ~35% in homozygotes, less severe than C677T but synergistic when compound heterozygous (677CT/1298AC).

Molecular Mechanism

The Glu429Ala substitution is in the S-adenosylmethionine regulatory domain of MTHFR. It reduces allosteric regulation rather than catalytic activity directly, making the enzyme less responsive to SAM feedback inhibition.

Peptide Therapeutic Relevance

Peptides targeting the SAM regulatory domain could restore normal feedback regulation. PepFold generates candidates exploring this allosteric region alongside the catalytic domain.

Gene: MTHFR (Methylenetetrahydrofolate Reductase)

Catalyzes conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary circulating form of folate. Essential for homocysteine remethylation and one-carbon metabolism.

Chromosome 1p36.22

Full MTHFR gene profile →

Condition: Hyperhomocysteinemia (MTHFR-related)

Elevated blood homocysteine due to MTHFR variants (C677T, A1298C) affecting folate metabolism. Associated with cardiovascular disease, neural tube defects, and potential cognitive effects. The most common pharmacogenomic condition worldwide.

Prevalence: 10-15% of most populations are TT homozygous for C677T; up to 25% in some Mediterranean populations

Full Hyperhomocysteinemia (MTHFR-related) profile →

Related Variants

rs1801133MTHFR — C677T (Ala222Val)

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