GUCA2A

protein-coding

guanylate cyclase activator 2A, the group of Receptor ligands

Gene summary

Predicted to enable guanylate cyclase activator activity. Predicted to be involved in signal transduction. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

GUCA2

MANE transcript

NM_033553.3

Inheritance

—

ClinVar variants

U:16B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr1:42,162,690-42,164,745

External References & Databases

Ensembl (ENSG00000197273)

Transcript & Mutation Effects

hg38 • Region Span ~2.1 kb

Loading mutation effect viewer...

GenCC 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 GUCA2A variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033553.3. 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			16 clinvar	1 clinvar		17
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	16	1	0	17

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033553.3	RefSeq	NP_291031.2	3	MANE Select
ENST00000357001.3	Ensembl	ENSP00000349493.2	3	MANE Select
ENST00000888051.1	Ensembl	ENSP00000558110.1	3	Standard
ENST00000888051.2	Ensembl	ENSP00000558110.1	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
regulation of signaling receptor activity
positive regulation of guanylate cyclase activity

Molecular Function

hormone activity
guanylate cyclase activator activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357001
Coding exons: 3
Length: 2028
Individuals with no LoFs: 124390
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124393
p: 0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.07	86	62.2	1.38	0.00000326	723
Missense (PolyPhen)		27	24.771	1.09		277
Synonymous	-1.11	35	27.6	1.27	0.00000176	225
Loss of Function	1.34	1	3.83	0.261	1.62e-7	47

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000055	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000089	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.520
RVIS EVS: 0.19
RVIS percentile EVS: 66.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0904

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium