GUCY1A2

protein-coding

guanylate cyclase 1 soluble subunit alpha 2, the group of Soluble guanylate cyclases

Gene summary

Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Previous symbols:

GUC1A2

MANE transcript

NM_000855.3

Inheritance

—

ClinVar variants

U:83B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr11:106,674,019-107,018,476

External References & Databases

Ensembl (ENSG00000152402)

Transcript & Mutation Effects

hg38 • Region Span ~344.5 kb

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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 GUCY1A2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000855.3. 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			1 clinvar		1 clinvar	2
missense			82 clinvar			82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	83	0	1	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000855.3	RefSeq	NP_000846.1	8	MANE Select
ENST00000526355.7	Ensembl	ENSP00000431245.2	8	MANE Select
NM_001256424.2	RefSeq	NP_001243353.1	9	Standard
ENST00000282249.6	Ensembl	ENSP00000282249.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Platelet activation - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Long-term depression - Homo sapiens (human)
Gap junction - Homo sapiens (human)
Circadian entrainment - Homo sapiens (human)

Biological Process

cGMP biosynthetic process
signal transduction
positive regulation of nitric oxide mediated signal transduction
intracellular signal transduction

Molecular Function

guanylate cyclase activity
protein binding
GTP binding
heme binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000282249
Coding exons: 9
Length: 344513
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125746
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.36	262	394	0.666	0.0000198	4981
Missense (PolyPhen)		50	140.09	0.35693		1702
Synonymous	0.179	146	149	0.981	0.00000765	1503
Loss of Function	3.93	7	30.3	0.231	0.00000186	357

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000075	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has guanylyl cyclase on binding to the beta-1 subunit.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.0879
RVIS EVS: -1.05
RVIS percentile EVS: 7.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.766

Gene Damage Prediction

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