GUCY1A1

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

Basic information

Region (hg38): 4:155666726-155737059

Previous symbols: [ "GUC1A3", "GUCY1A3" ]

Links

ENSG00000164116 ∙ NCBI:2982 ∙ OMIM:139396 ∙ HGNC:4685 ∙ Uniprot:Q02108 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Moyamoya disease with early-onset achalasia (Strong), mode of inheritance: AR
• Moyamoya disease with early-onset achalasia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Moyamoya disease 6 with or without achalasia	AR	Cardiovascular	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	Cardiovascular; Gastrointestinal	24581742

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GUCY1A1 gene.

• Moyamoya disease with early-onset achalasia (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUCY1A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				12	4	16
missense			37	3	2	42
nonsense		1				1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region					1	1
non coding			6	8	5	19
Total	2	1	43	23	11

Highest pathogenic variant AF is 0.0000131

Variants in GUCY1A1

This is a list of pathogenic ClinVar variants found in the GUCY1A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-155696879-G-A			Likely benign (Feb 20, 2018)
4-155696895-A-C		not specified	Uncertain significance (Dec 13, 2023)
4-155696903-A-G			Likely benign (Sep 15, 2021)
4-155696936-T-A			Uncertain significance (-)
4-155696940-G-A			Benign (Jan 15, 2024)
4-155696949-G-A		not specified	Uncertain significance (Feb 02, 2022)
4-155696960-G-T		not specified	Uncertain significance (Dec 08, 2023)
4-155696975-C-T			Likely benign (Aug 30, 2023)
4-155696977-C-T		not specified	Uncertain significance (Jun 17, 2024)
4-155696994-A-G		not specified	Uncertain significance (Sep 22, 2023)
4-155696996-C-T		not specified	Likely benign (May 08, 2024)
4-155697037-A-C		GUCY1A1-related disorder	Benign (Jan 13, 2024)
4-155697063-C-T		not specified	Uncertain significance (Jul 12, 2023)
4-155697064-G-A		not specified	Uncertain significance (Jul 30, 2023)
4-155697131-G-A			Likely benign (Sep 25, 2023)
4-155697142-A-T			Benign (Dec 10, 2023)
4-155703945-A-C		not specified	Uncertain significance (Aug 24, 2023)
4-155703948-T-C		not specified	Uncertain significance (May 17, 2021)
4-155708248-AAG-A		Moyamoya disease with early-onset achalasia • Moyamoya disease 1 • See cases • not specified	Conflicting classifications of pathogenicity (May 18, 2021)
4-155708256-A-C		not specified	Uncertain significance (May 03, 2023)
4-155708284-A-G			Benign (Oct 03, 2023)
4-155708311-T-A			Likely benign (Jun 21, 2023)
4-155710530-A-G			Likely benign (Nov 06, 2023)
4-155710551-T-C		not specified	Uncertain significance (Aug 22, 2023)
4-155710555-G-A			Likely benign (Jun 29, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GUCY1A1	protein_coding	protein_coding	ENST00000296518	8	65639

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.13e-8	0.983	125700	0	47	125747	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.681	334	371	0.900	0.0000190	4549
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000588	0.000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.000327	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000222	0.000220
Middle Eastern	0.000327	0.000326
South Asian	0.0000991	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Pathway: 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);Vascular smooth muscle contraction - Homo sapiens (human);Renin secretion - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Purine metabolism - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;NO-cGMP-PKG mediated Neuroprotection;Phosphodiesterases in neuronal function;ion channels and their functional role in vascular endothelium;Purine metabolism;actions of nitric oxide in the heart;Purine nucleotides nucleosides metabolism;Hemostasis;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• rvis_EVS: -1
• rvis_percentile_EVS: 8.47

Haploinsufficiency Scores

• pHI: 0.133
• hipred: Y
• hipred_score: 0.593
• ghis: 0.564

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Gucy1a1
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: cGMP biosynthetic process;nitric oxide mediated signal transduction;blood circulation;regulation of blood pressure;positive regulation of nitric oxide mediated signal transduction;response to defense-related host nitric oxide production;relaxation of vascular smooth muscle;retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission
• Cellular component: guanylate cyclase complex, soluble;glutamatergic synapse;GABA-ergic synapse
• Molecular function: guanylate cyclase activity;protein binding;GTP binding;heme binding;signaling receptor activity