GUCY2C
Chr 12ADARguanylate cyclase 2C
Also known as: DIAR6, GC-C, GCC, GUC2C, HSER, MECIL, MUCIL, STAR
This protein is a transmembrane guanylyl cyclase that synthesizes cyclic GMP from GTP and serves as a receptor for endogenous peptides guanylin and uroguanylin. Mutations cause familial diarrhea with autosomal dominant inheritance and meconium ileus with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (LOEUF 1.079), suggesting different mutation types may underlie the distinct clinical presentations and inheritance patterns.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
600 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 | 0 | 1 | 9 | 0 | 10 |
Likely Pathogenic | 1 | 2 | 0 | 0 | 3 |
VUS | 22 | 289 | 39 | 7 | 357 |
Likely Benign | 0 | 1 | 105 | 102 | 208 |
Benign | 0 | 0 | 5 | 0 | 5 |
Conflicting | — | 4 | |||
| Total | 23 | 293 | 158 | 109 | 587 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GUCY2C · 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
External Resources
Links to major genomics databases and tools