GUCY1A1
Chr 4ARguanylate cyclase 1 soluble subunit alpha 1
Also known as: GC-S-alpha-1, GC-SA3, GCS-alpha-3, GUC1A3, GUCA3, GUCSA3, GUCY1A3, MYMY6
The encoded protein is the alpha subunit of soluble guanylate cyclase, which forms a heterodimeric enzyme with a beta subunit to catalyze the conversion of GTP to cyclic GMP in response to nitric oxide signaling. Biallelic mutations cause Moyamoya disease 6 with achalasia, an autosomal recessive condition affecting cerebral vasculature and esophageal motility. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.84).
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
225 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 5 | 1 | 33 | 0 | 39 |
Likely Pathogenic | 2 | 0 | 5 | 0 | 7 |
VUS | 1 | 92 | 9 | 1 | 103 |
Likely Benign | 0 | 7 | 9 | 22 | 38 |
Benign | 0 | 3 | 6 | 3 | 12 |
Conflicting | — | 2 | |||
| Total | 8 | 103 | 62 | 26 | 201 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GUCY1A1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools