Can PepFold design peptides for rs4680?

Yes. PepFold accepts rs4680 as input, annotates it via ClinVar, maps it to the COMT 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

rs4680 — COMT Val158Met

Q: What gene is rs4680 in?

rs4680 is a variant in the COMT (Catechol-O-Methyltransferase) gene located on chromosome 22q11.21. Degrades catecholamines (dopamine, epinephrine, norepinephrine) in the prefrontal cortex. The Val/Met polymorphism creates a spectrum of dopamine metabolism rates affecting cognition, pain, and stress response.

Q: What is the clinical significance of rs4680?

rs4680 is classified as "Drug response / Risk factor" in ClinVar. The Val158Met substitution makes COMT thermolabile at 37°C. Met/Met individuals have higher prefrontal dopamine levels (better working memory) but lower pain tolerance and increased anxiety. This directly impacts analgesic peptide design.

Drug response / Risk factor · ~50% global (Met allele)

rs4680 (Val158Met) affects catechol-O-methyltransferase activity, influencing dopamine, epinephrine, and norepinephrine metabolism. The Met allele reduces COMT activity 3-4 fold, associated with increased pain sensitivity, stress response, and variable opioid requirements.

Molecular Mechanism

The Val158Met substitution makes COMT thermolabile at 37°C. Met/Met individuals have higher prefrontal dopamine levels (better working memory) but lower pain tolerance and increased anxiety. This directly impacts analgesic peptide design.

Peptide Therapeutic Relevance

Opioid peptide analogs and COMT-stabilizing peptides are active research areas. PepFold generates candidates considering the Val/Met status to design genotype-informed analgesic peptides.

Gene: COMT (Catechol-O-Methyltransferase)

Degrades catecholamines (dopamine, epinephrine, norepinephrine) in the prefrontal cortex. The Val/Met polymorphism creates a spectrum of dopamine metabolism rates affecting cognition, pain, and stress response.

Chromosome 22q11.21

Full COMT gene profile →

Condition: Pain Sensitivity and Opioid Response (COMT/OPRM1)

Genetic variation in COMT (Val158Met) and OPRM1 (A118G) creates a wide spectrum of pain sensitivity and opioid analgesic requirements. Personalized pain management is one of the most promising applications of pharmacogenomics.

Prevalence: Up to 40% variance in opioid requirements is genetically determined

Full Pain Sensitivity and Opioid Response (COMT/OPRM1) profile →

Analyze rs4680 with PepFold

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