PDE3A

phosphodiesterase 3A, the group of Phosphodiesterases

Basic information

Region (hg38): 12:20368536-20688583

Links

ENSG00000172572 ∙ NCBI:5139 ∙ OMIM:123805 ∙ HGNC:8778 ∙ Uniprot:Q14432 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• brachydactyly-arterial hypertension syndrome (Strong), mode of inheritance: AD
• brachydactyly-arterial hypertension syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypertension with brachydactyly syndrome	AD	Cardiovascular	Individuals have been described as suffering from death by stroke by age 50 when untreated, and awareness may allow early management of hypertension, which has been described as having onset in childhood	Cardiovascular; Musculoskeletal	4774535; 9415685; 25961942

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE3A gene.

• not provided (127 variants)
• Inborn genetic diseases (39 variants)
• Brachydactyly-arterial hypertension syndrome (9 variants)
• not specified (4 variants)
• PDE3A-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE3A 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			2	20	15	37
missense	2	1	60	7	6	76
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding				4	45	49
Total	2	1	64	32	66

Variants in PDE3A

This is a list of pathogenic ClinVar variants found in the PDE3A region.

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

Position	Type	Phenotype	Significance	ClinVar
12-20369180-A-AGCGT			Benign (Jun 19, 2021)
12-20369190-CGTGT-C			Benign (Jun 19, 2021)
12-20369190-C-CGT			Benign (Jun 21, 2021)
12-20369279-T-G		PDE3A-related disorder	Benign (Jun 07, 2019)
12-20369289-C-T			Uncertain significance (Jul 17, 2023)
12-20369308-A-G		PDE3A-related disorder	Benign (Sep 13, 2022)
12-20369309-C-G		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
12-20369318-G-A			Benign (Jan 31, 2024)
12-20369330-C-T		Inborn genetic diseases	Uncertain significance (Apr 13, 2023)
12-20369357-G-A			Uncertain significance (Mar 20, 2023)
12-20369361-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
12-20369364-G-A		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
12-20369375-C-T		Inborn genetic diseases	Uncertain significance (Mar 13, 2023)
12-20369387-C-T		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
12-20369425-G-A			Uncertain significance (Jun 01, 2021)
12-20369453-A-G		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
12-20369484-C-T			Uncertain significance (May 20, 2022)
12-20369496-C-G			Uncertain significance (Feb 01, 2024)
12-20369514-T-A		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
12-20369515-G-A			Benign (Jan 15, 2024)
12-20369526-T-C		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
12-20369530-C-T			Likely benign (Aug 10, 2022)
12-20369553-A-G		PDE3A-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 27, 2024)
12-20369565-A-AGGC			Likely benign (Oct 20, 2023)
12-20369569-G-A			Benign (Jan 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE3A	protein_coding	protein_coding	ENST00000359062	16	315137

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000193	1.00	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.592	586	628	0.933	0.0000313	7379
Missense in Polyphen		121	202.59	0.59725		2297
Synonymous	-2.00	296	255	1.16	0.0000135	2322
Loss of Function	4.13	15	44.8	0.335	0.00000207	555

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000894	0.000858
Ashkenazi Jewish	0.00	0.00
East Asian	0.000660	0.000598
Finnish	0.0000978	0.0000924
European (Non-Finnish)	0.000245	0.000229
Middle Eastern	0.000660	0.000598
South Asian	0.000263	0.000261
Other	0.000333	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cyclic nucleotide phosphodiesterase with a dual- specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. {ECO:0000250|UniProtKB:Q9Z0X4}.
• Disease: DISEASE: Hypertension and brachydactyly syndrome (HTNB) [MIM:112410]: A syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. {ECO:0000269|PubMed:25961942}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Renin secretion - Homo sapiens (human);Purine metabolism - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;NO-cGMP-PKG mediated Neuroprotection;Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;actions of nitric oxide in the heart;Purine nucleotides nucleosides metabolism;Hemostasis;Leptin;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.399
• rvis_EVS: -1.1
• rvis_percentile_EVS: 6.89

Haploinsufficiency Scores

• pHI: 0.0948
• hipred: Y
• hipred_score: 0.746
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.956

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde3a
• Phenotype: normal phenotype; reproductive system phenotype

Gene ontology

• Biological process: oocyte maturation;lipid metabolic process;G protein-coupled receptor signaling pathway;cAMP-mediated signaling;cGMP-mediated signaling;regulation of meiotic nuclear division;response to drug;negative regulation of apoptotic process;negative regulation of vascular permeability;positive regulation of vascular permeability;negative regulation of cAMP-mediated signaling;positive regulation of oocyte development;cellular response to cGMP;cellular response to transforming growth factor beta stimulus
• Cellular component: cytosol;integral component of membrane
• Molecular function: 3',5'-cyclic-AMP phosphodiesterase activity;cGMP-inhibited cyclic-nucleotide phosphodiesterase activity;protein binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity