GUCA2B

Chr 1

guanylate cyclase activator 2B

Also known as: GCAP-II, UGN

The protein encoded by this gene is processed to generate uroguanylin, an endogenous activator of intestinal guanylate cyclase that regulates fluid and electrolyte transport in the intestine and kidneys by stimulating cyclic GMP production. Mutations in GUCA2B cause autosomal recessive meconium ileus, a neonatal intestinal obstruction disorder affecting newborns. The gene shows moderate tolerance to loss-of-function variants with relatively high constraint metrics.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.98
Clinical SummaryGUCA2B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.381
Z-score 1.62
OE 0.21 (0.070.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.32Z-score
OE missense 0.89 (0.721.10)
61 obs / 68.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.070.98)
00.351.4
Missense OE0.89 (0.721.10)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 1 / 4.8Missense obs/exp: 61 / 68.5Syn Z: -0.76
DN
0.5082th %ile
GOF
0.6640th %ile
LOF
0.3356th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GUCA2B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗