PDE4A

phosphodiesterase 4A, the group of Phosphodiesterases

Basic information

Region (hg38): 19:10416772-10469630

Previous symbols: [ "DPDE2" ]

Links

ENSG00000065989 ∙ NCBI:5141 ∙ OMIM:600126 ∙ HGNC:8780 ∙ Uniprot:P27815 ∙ 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 PDE4A gene.

• Inborn genetic diseases (19 variants)
• not provided (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE4A 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	5	9
missense			18	3	1	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	18	7	6

Variants in PDE4A

This is a list of pathogenic ClinVar variants found in the PDE4A region.

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

Position	Type	Phenotype	Significance	ClinVar
19-10417700-T-A			Uncertain significance (-)
19-10420798-C-G		not specified	Uncertain significance (Sep 16, 2021)
19-10420815-C-T			Benign (Aug 22, 2018)
19-10420824-G-C			Benign (Aug 14, 2018)
19-10449096-G-A		not specified	Uncertain significance (Sep 16, 2021)
19-10449102-T-C		not specified	Uncertain significance (Aug 30, 2021)
19-10450899-C-T			Likely benign (Mar 01, 2022)
19-10450945-T-G			Benign (Aug 14, 2018)
19-10454882-C-T			Benign (Dec 31, 2019)
19-10457893-G-A		not specified	Uncertain significance (Jul 19, 2023)
19-10457912-C-T		not specified	Uncertain significance (Mar 29, 2022)
19-10457945-G-A		not specified	Uncertain significance (Jun 28, 2022)
19-10457969-C-T		not specified	Uncertain significance (May 31, 2022)
19-10457992-C-T			Benign/Likely benign (Dec 31, 2019)
19-10459411-C-T			Likely benign (Dec 31, 2019)
19-10459474-C-T			Likely benign (Mar 28, 2018)
19-10459656-C-T		not specified	Uncertain significance (Aug 02, 2021)
19-10459676-G-A		not specified	Uncertain significance (May 11, 2022)
19-10459733-G-A		not specified	Uncertain significance (May 25, 2022)
19-10461083-A-G		not specified	Uncertain significance (Feb 27, 2024)
19-10461628-A-G		not specified	Uncertain significance (Dec 15, 2023)
19-10461908-C-T		not specified	Uncertain significance (Nov 14, 2023)
19-10463800-G-A		not specified	Uncertain significance (Aug 30, 2022)
19-10463819-C-T			Benign (Dec 31, 2019)
19-10463832-C-G		not specified	Uncertain significance (Aug 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE4A	protein_coding	protein_coding	ENST00000352831	15	52857

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.982	0.0183	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.42	383	541	0.708	0.0000336	5699
Missense in Polyphen		100	190.32	0.52544		1983
Synonymous	0.448	227	236	0.963	0.0000160	1801
Loss of Function	4.63	5	34.2	0.146	0.00000191	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000141	0.0000924
European (Non-Finnish)	0.0000365	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:11566027, ECO:0000269|PubMed:17727341}.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;G Protein Signaling Pathways;Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;DARPP-32 events;Purine nucleotides nucleosides metabolism;Opioid Signalling;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.422
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.86

Haploinsufficiency Scores

• pHI: 0.0852
• hipred: Y
• hipred_score: 0.711
• ghis: 0.617

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde4a
• Phenotype: taste/olfaction phenotype

Gene ontology

• Biological process: cAMP catabolic process;signal transduction;G protein-coupled receptor signaling pathway;sensory perception of smell;regulation of protein kinase A signaling;cellular response to drug;regulation of cAMP-mediated signaling
• Cellular component: nucleoplasm;cytosol;plasma membrane;membrane;ruffle membrane;perinuclear region of cytoplasm
• Molecular function: 3',5'-cyclic-AMP phosphodiesterase activity;protein binding;cAMP binding;metal ion binding