GUCY1B1

protein-coding

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

Gene summary

This gene encodes the beta subunit of the soluble guanylate cyclase (sGC), which catalyzes the conversion of GTP (guanosine triphosphate) to cGMP (cyclic guanosine monophosphate). The encoded protein contains an HNOX domain, which serves as a receptor for ligands such as nitric oxide, oxygen and nitrovasodilator drugs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

Previous symbols:

GUC1B3
GUCY1B3

MANE transcript

NM_000857.5

Inheritance

—

ClinVar variants

U:45

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr4:155,758,992-155,807,811

External References & Databases

Ensembl (ENSG00000061918)

Transcript & Mutation Effects

hg38 • Region Span ~48.8 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 GUCY1B1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 42

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000857.5. 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
missense			43 clinvar			43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	45	0	0	45

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000857.5	RefSeq	NP_000848.1	14	MANE Select
ENST00000264424.13	Ensembl	ENSP00000264424.8	14	MANE Select
NM_001291951.3	RefSeq	NP_001278880.1	15	Standard
NM_001291952.3	RefSeq	NP_001278881.1	13	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
cGMP-mediated signaling
nitric oxide-cGMP-mediated signaling pathway

Molecular Function

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

Cellular Component

guanylate cyclase complex, soluble
presynaptic active zone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264424
Coding exons: 14
Length: 48600
Individuals with no LoFs: 124641
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 124658
p: 0.0000682

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.12	173	333	0.519	0.0000171	4082
Missense (PolyPhen)		42	119.99	0.35002		1443
Synonymous	-0.324	121	117	1.04	0.00000585	1163
Loss of Function	2.95	13	30.6	0.424	0.00000162	388

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000093	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000080	0.000080	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP. {ECO:0000250|UniProtKB:P16068, ECO:0000269|PubMed:1352257}.;

Recessive Scores

pRec: 0.138

Intolerance Scores

RVIS EVS: -0.56
RVIS percentile EVS: 19.54

Essentials

Essential (gene trap): N