GUCA2B
protein-codingguanylate cyclase activator 2B, the group of Receptor ligands
Gene summary
This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products, including uroguanylin, a member of the guanylin family of peptides and an endogenous ligand of the guanylate cyclase-C receptor. Binding of this peptide to its cognate receptor stimulates an increase in cyclic GMP and may regulate salt and water homeostasis in the intestine and kidneys. [provided by RefSeq, Nov 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GUCA2B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007102.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 10 | 4 | 14 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 10 | 4 | 0 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009033.1 | 3 | MANE Select | |
| Ensembl | ENSP00000361662.1 | 3 | MANE Select | |
| Ensembl | ENSP00000765150.1 | 3 | Standard | |
| Ensembl | ENSP00000810064.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Myometrial Relaxation and Contraction Pathways
- Digestion
- Digestion and absorption
Biological Process
- digestion
- excretion
- body fluid secretion
- cGMP-mediated signaling
- positive regulation of guanylate cyclase activity
Molecular Function
- calcium sensitive guanylate cyclase activator activity
- guanylate cyclase activator activity
Cellular Component
- photoreceptor outer segment
- extracellular region
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372581
- Coding exons
- 3
- Length
- 2404
- Individuals with no LoFs
- 123366
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123367
- p
- 0.00000405
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.322 | 61 | 68.5 | 0.891 | 0.00000420 | 705 |
| Missense (PolyPhen) | 19 | 18.984 | 1.0009 | 225 | ||
| Synonymous | -0.760 | 39 | 33.4 | 1.17 | 0.00000246 | 241 |
| Loss of Function | 1.62 | 1 | 4.84 | 0.206 | 2.08e-7 | 50 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins. May be a potent physiological regulator of intestinal fluid and electrolyte transport. May be an autocrine/paracrine regulator of intestinal salt and water transport.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.154
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 68.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0525
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |