PDE5A

phosphodiesterase 5A, the group of Phosphodiesterases

Basic information

Region (hg38): 4:119494396-119628804

Links

ENSG00000138735 ∙ NCBI:8654 ∙ OMIM:603310 ∙ HGNC:8784 ∙ Uniprot:O76074 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE5A gene.

• Inborn genetic diseases (17 variants)
• not provided (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE5A 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				4	4	8
missense			16	3	3	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	16	7	7

Variants in PDE5A

This is a list of pathogenic ClinVar variants found in the PDE5A region.

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

Position	Type	Phenotype	Significance	ClinVar
4-119498633-T-C		not specified	Uncertain significance (May 22, 2023)
4-119501164-A-AAAT			Benign (Jun 08, 2018)
4-119501236-C-T			Benign (Jun 13, 2018)
4-119502583-T-A		not specified	Uncertain significance (Jan 31, 2024)
4-119502607-T-G			Benign (Mar 01, 2018)
4-119502610-C-T		not specified	Uncertain significance (Aug 30, 2021)
4-119502636-G-C		not specified	Likely benign (Aug 12, 2021)
4-119502654-A-G			Likely benign (Jun 16, 2018)
4-119504547-T-C		not specified	Uncertain significance (Jun 30, 2022)
4-119505903-C-T			Likely benign (Jul 10, 2018)
4-119505936-C-T			Benign (Feb 09, 2018)
4-119511122-T-G			Benign (Apr 10, 2018)
4-119511125-A-G			Likely benign (Apr 01, 2022)
4-119519083-A-G			Likely benign (Jul 17, 2018)
4-119519102-A-G		not specified	Uncertain significance (Jan 08, 2024)
4-119519123-A-G			Benign (Jan 19, 2018)
4-119521050-C-T		not specified	Uncertain significance (Nov 01, 2022)
4-119525571-T-C		not specified	Uncertain significance (Jun 13, 2022)
4-119542576-G-T		not specified	Uncertain significance (Jan 09, 2024)
4-119542593-T-G			Benign (Feb 08, 2018)
4-119542606-C-T			Benign/Likely benign (Feb 01, 2024)
4-119542623-G-T		not specified	Uncertain significance (May 04, 2022)
4-119552585-G-A		not specified	Uncertain significance (Aug 10, 2023)
4-119552613-G-C		not specified	Uncertain significance (Dec 01, 2022)
4-119552622-T-C		not specified	Uncertain significance (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE5A	protein_coding	protein_coding	ENST00000354960	21	134597

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000106	1.00	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.10	327	453	0.722	0.0000224	5828
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000489	0.000460
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000163	0.000163
Finnish	0.000232	0.000231
European (Non-Finnish)	0.000216	0.000211
Middle Eastern	0.000163	0.000163
South Asian	0.000113	0.0000980
Other	0.000327	0.000326

dbNSFP

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}.
• Pathway: Purine metabolism - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Phosphodiesterases in neuronal function;Purine nucleotides nucleosides metabolism;Hemostasis;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.238

Intolerance Scores

• loftool: 0.457
• rvis_EVS: 1.05
• rvis_percentile_EVS: 91.34

Haploinsufficiency Scores

• pHI: 0.178
• hipred: Y
• hipred_score: 0.641
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.443

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde5a

Gene ontology

• 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;cGMP catabolic process;negative regulation of cardiac muscle contraction;relaxation of cardiac muscle;positive regulation of oocyte development
• Cellular component: cellular_component;cytosol
• Molecular function: 3',5'-cyclic-nucleotide phosphodiesterase activity;protein binding;cGMP binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity