GUCY1B1

Chr 4

guanylate cyclase 1 soluble subunit beta 1

Also known as: GC-S-beta-1, GC-SB3, GUC1B3, GUCB3, GUCSB3, GUCY1B3

NCBI Gene: 2983ENSG00000061918UniProt: Q02153

The protein is the beta subunit of soluble guanylate cyclase, which catalyzes the conversion of GTP to cGMP and mediates cellular responses to nitric oxide through an HNOX domain that serves as a receptor for nitric oxide, oxygen, and nitrovasodilator drugs. Mutations cause autosomal recessive moyamoya angiopathy with early-onset stroke, typically presenting in childhood with cerebrovascular disease. The gene shows very low constraint against loss-of-function variants (pLI = 0.000026), consistent with the recessive inheritance pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
30
P/LP submissions
0%
P/LP missense
0.68
LOEUF
GOF
Mechanism· predicted
Clinical Summary— GUCY1B1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 52 VUS of 94 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 2.95
OE 0.42 (0.28–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
3.12Z-score
OE missense 0.52 (0.46–0.59)
173 obs / 333.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.42 (0.28–0.68)
0≤0.351.4
Missense OE0.52 (0.46–0.59)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 13 / 30.6Missense obs/exp: 173 / 333.4Syn Z: -0.32
DN
0.5771th %ile
GOF
0.73top 25%
LOF
0.3843th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic4
VUS52
26
Pathogenic
4
Likely Pathogenic
52
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
4
0
4
VUS
0
42
10
0
52
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04240082

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GUCY1B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients