PDE4D

phosphodiesterase 4D, the group of Phosphodiesterases|MicroRNA protein coding host genes

Basic information

Region (hg38): 5:58969037-60522120

Previous symbols: [ "DPDE3" ]

Links

ENSG00000113448 ∙ NCBI:5144 ∙ OMIM:600129 ∙ HGNC:8783 ∙ Uniprot:Q08499 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Acrodysostosis 1 with or without hormone resistance (Definitive), mode of inheritance: AD
• acrodysostosis 2 with or without hormone resistance (Moderate), mode of inheritance: AD
• acrodysostosis (Supportive), mode of inheritance: AD
• acrodysostosis with multiple hormone resistance (Supportive), mode of inheritance: AD
• chromosome 5q12 deletion syndrome (Supportive), mode of inheritance: Unknown
• acrodysostosis 2 with or without hormone resistance (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acrodysostosis 2, with or without hormone resistance	AD	Cardiovascular; Endocrine	Individuals have been described with cardiovascular anomalies, including deep vein thrombosis, and awareness may allow early recognition and treatment; Individuals have been described with endocrine anomalies, including parathyroid hormone resistance and hypogonadism, and awareness may allow surveillance and early medical interventions	Cardiovascular;Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	11200992; 22464252; 22464250; 22464252; 23033274; 24203977

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE4D gene.

• not provided (273 variants)
• Acrodysostosis 2 with or without hormone resistance (150 variants)
• Acrodysostosis (24 variants)
• Inborn genetic diseases (22 variants)
• PDE4D-related condition (4 variants)
• not specified (3 variants)
• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE4D 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			3	42	6	51
missense	6	6	91	6	4	113
nonsense			1			1
start loss			1			1
frameshift			5			5
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)						0
splice region			4	9	4	17
non coding			66	39	128	233
Total	6	7	169	87	138

Variants in PDE4D

This is a list of pathogenic ClinVar variants found in the PDE4D region.

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

Position	Type	Phenotype	Significance	ClinVar
5-58969119-G-T		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 12, 2018)
5-58969251-C-G		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)
5-58969360-G-A		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 13, 2018)
5-58969369-C-A		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)
5-58969381-T-C		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 12, 2018)
5-58969404-A-G		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 13, 2018)
5-58969423-A-G		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 13, 2018)
5-58969463-C-T		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 12, 2018)
5-58969474-T-C		Acrodysostosis	Uncertain significance (Jun 14, 2016)
5-58969539-G-A		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 13, 2018)
5-58969546-A-C		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 12, 2018)
5-58969664-T-C		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)
5-58969683-G-C		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 12, 2018)
5-58969699-C-A		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 12, 2018)
5-58969749-G-A		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 13, 2018)
5-58969778-T-G		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)
5-58969937-G-C		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)
5-58969961-T-C		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 12, 2018)
5-58969989-C-T		Acrodysostosis 2 with or without hormone resistance	Likely benign (Jan 13, 2018)
5-58970004-G-A		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 12, 2018)
5-58970005-A-C		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 12, 2018)
5-58970042-C-A		Acrodysostosis 2 with or without hormone resistance	Benign (Jan 12, 2018)
5-58970135-G-A		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)
5-58970140-G-A		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 15, 2018)
5-58970151-G-A		Acrodysostosis 2 with or without hormone resistance	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE4D	protein_coding	protein_coding	ENST00000340635	15	1553083

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000198	124878	0	9	124887	0.0000360

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.75	190	402	0.473	0.0000209	5309
Missense in Polyphen		39	152.95	0.25498		1969
Synonymous	0.953	131	146	0.900	0.00000745	1540
Loss of Function	5.23	3	37.6	0.0798	0.00000219	439

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000631	0.0000619
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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:15260978, ECO:0000269|PubMed:15576036}.
• Disease: DISEASE: Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. {ECO:0000269|PubMed:17006457}.; DISEASE: Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems. {ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252, ECO:0000269|PubMed:23033274, ECO:0000269|PubMed:23043190}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Dipyridamole (Antiplatelet) Action Pathway;Cilostazol Action Pathway;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Myometrial Relaxation and Contraction Pathways;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: 0.345

Intolerance Scores

• loftool: 0.327
• rvis_EVS: -1.38
• rvis_percentile_EVS: 4.39

Haploinsufficiency Scores

• pHI: 0.245
• hipred: Y
• hipred_score: 0.786
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde4d
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: pde4d
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: regulation of heart rate;cAMP catabolic process;smooth muscle contraction;G protein-coupled receptor signaling pathway;aging;regulation of signaling receptor activity;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;cAMP-mediated signaling;neutrophil chemotaxis;positive regulation of interferon-gamma production;positive regulation of interleukin-2 production;positive regulation of interleukin-5 production;negative regulation of peptidyl-serine phosphorylation;multicellular organism growth;negative regulation of cAMP-mediated signaling;negative regulation of heart contraction;T cell receptor signaling pathway;regulation of ryanodine-sensitive calcium-release channel activity;establishment of endothelial barrier;cellular response to lipopolysaccharide;cellular response to epinephrine stimulus;adrenergic receptor signaling pathway;regulation of cardiac muscle cell contraction;adenylate cyclase-activating adrenergic receptor signaling pathway involved in positive regulation of heart rate;regulation of cell communication by electrical coupling involved in cardiac conduction;negative regulation of relaxation of cardiac muscle
• Cellular component: centrosome;cytosol;plasma membrane;voltage-gated calcium channel complex;apical plasma membrane;nuclear membrane;calcium channel complex
• Molecular function: 3',5'-cyclic-nucleotide phosphodiesterase activity;3',5'-cyclic-AMP phosphodiesterase activity;protein binding;drug binding;enzyme binding;cAMP binding;beta-2 adrenergic receptor binding;ion channel binding;metal ion binding;ATPase binding;scaffold protein binding