PDE5A

protein-coding

phosphodiesterase 5A, the group of Phosphodiesterases

Gene summary

This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001083.4

Inheritance

—

ClinVar variants

U:106B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr4:119,494,397-119,628,804

External References & Databases

Ensembl (ENSG00000138735)

Transcript & Mutation Effects

hg38 • Region Span ~134.4 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 PDE5A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001083.4. 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			2 clinvar	5 clinvar	3 clinvar	10
missense			99 clinvar	5 clinvar	2 clinvar	106
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	106	10	5	121

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001083.4	RefSeq	NP_001074.2	21	MANE Select
ENST00000354960.8	Ensembl	ENSP00000347046.3	21	MANE Select
NM_033430.3	RefSeq	NP_236914.2	21	Standard
NM_033437.4	RefSeq	NP_246273.2	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
cGMP-PKG signaling pathway - Homo sapiens (human)
Phosphodiesterases in neuronal function
Purine nucleotides nucleosides metabolism
Hemostasis

Biological Process

signal transduction
positive regulation of cardiac muscle hypertrophy
regulation of nitric oxide mediated signal transduction
negative regulation of T cell proliferation
positive regulation of MAP kinase activity

Molecular Function

3',5'-cyclic-nucleotide phosphodiesterase activity
protein binding
cGMP binding
metal ion binding
3',5'-cyclic-GMP phosphodiesterase activity

Cellular Component

cellular_component
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354960
Coding exons: 21
Length: 134597
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.10	327	453	0.722	0.0000224	5828
Missense (PolyPhen)		96	169.63	0.56595		2206
Synonymous	1.33	136	157	0.865	0.00000777	1532
Loss of Function	4.25	16	47.6	0.336	0.00000235	588

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00043	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00022	0.00021	rare
South Asian	0.00011	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'- GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334). {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9714779}.;

Recessive Scores

pRec: 0.238

Intolerance Scores

LoFtool: 0.457
RVIS EVS: 1.05
RVIS percentile EVS: 91.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.443

Gene Damage Prediction

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