GUCY1A1

protein-coding

guanylate cyclase 1 soluble subunit alpha 1, 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. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Previous symbols:

GUC1A3
GUCY1A3

MANE transcript

NM_001130682.3

Inheritance

ClinVar variants

P:18U:110B:36

Top phenotype

Moyamoya disease 6 with or without achalasia

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr4:155,666,726-155,737,059

External References & Databases

Ensembl (ENSG00000164116)

Transcript & Mutation Effects

hg38 • Region Span ~70.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Moyamoya disease with early-onset achalasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014331

Submitter: PanelApp Australia

Moyamoya disease with early-onset achalasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014331

Submitter: Genomics England PanelApp

Moyamoya disease with early-onset achalasiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014331

Submitter: Orphanet

Clinical Genomic Database (CGD)

Moyamoya disease 6 with or without achalasiaAR

Manifestation: Cardiovascular; Gastrointestinal

Intervention: Cardiovascular

Rationale: Surveillance for cardiovascular complications, as well as related preventive measures to help control contributory factors and clinical manifestations (eg, hypertension) may reduce morbidity and mortality

Refs: 24581742; 26777256

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GUCY1A1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 67

Moyamoya disease with early-onset achalasiaTotal: 16

GUCY1A1-related disorderTotal: 4

Moyamoya disease 1Total: 3

Myocardial infarction, susceptibility to, 1Total: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001130682.3. 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			3 clinvar	25 clinvar	3 clinvar	31
missense	1 clinvar		102 clinvar	6 clinvar	2 clinvar	111
nonsense	5 clinvar	1 clinvar				6
start loss						0
frameshift	4 clinvar	3 clinvar				7
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	5 clinvar			9
Total	11	7	110	31	5	164

Highest pathogenic variant AF is 0.000033156015

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 125 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001130682.3	RefSeq	NP_001124154.1	8	MANE Select
ENST00000506455.6	Ensembl	ENSP00000424361.1	8	MANE Select
NM_000856.6	RefSeq	NP_000847.2	8	Standard
NM_001130683.4	RefSeq	NP_001124155.1	8	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
nitric oxide mediated signal transduction
blood circulation
regulation of blood pressure
positive regulation of nitric oxide mediated signal transduction

Molecular Function

guanylate cyclase activity
protein binding
GTP binding
heme binding
signaling receptor activity

Cellular Component

guanylate cyclase complex, soluble
glutamatergic synapse
GABA-ergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296518
Coding exons: 8
Length: 65639
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125747
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.681	334	371	0.900	0.0000190	4549
Missense (PolyPhen)		108	147.21	0.73364		1814
Synonymous	-0.295	148	144	1.03	0.00000814	1322
Loss of Function	2.25	17	30.4	0.560	0.00000190	344

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.000099	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.142

Intolerance Scores

RVIS EVS: -1
RVIS percentile EVS: 8.47

Essentials

Essential (gene trap): N