PDE11A

phosphodiesterase 11A, the group of Phosphodiesterases

Basic information

Region (hg38): 2:177623243-178108339

Links

ENSG00000128655 ∙ NCBI:50940 ∙ OMIM:604961 ∙ HGNC:8773 ∙ Uniprot:Q9HCR9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pigmented nodular adrenocortical disease, primary, 2 (Strong), mode of inheritance: AD
• pigmented nodular adrenocortical disease, primary, 2 (Limited), mode of inheritance: AD
• primary pigmented nodular adrenocortical disease (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pigmented nodular adrenocortical disease, primary, 2	AD	Endocrine	Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial	Endocrine	16767104; 20351491; 21115159

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE11A gene.

• not provided (67 variants)
• Inborn genetic diseases (36 variants)
• Pigmented nodular adrenocortical disease, primary, 2 (34 variants)
• not specified (4 variants)
• PDE11A-related condition (2 variants)
• Bardet-Biedl syndrome 16 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE11A 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				14	12	26
missense			58	3	5	66
nonsense		3	2			5
start loss						0
frameshift		5	5			10
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)		1	3	1		5
splice region				1	3	4
non coding				1	5	6
Total	0	9	69	19	23

Highest pathogenic variant AF is 0.00258

Variants in PDE11A

This is a list of pathogenic ClinVar variants found in the PDE11A region.

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

Position	Type	Phenotype	Significance	ClinVar
2-177629409-A-G		PDE11A-related disorder	Uncertain significance (Feb 29, 2024)
2-177629445-G-GGGA		Pigmented nodular adrenocortical disease, primary, 2	Benign (Sep 05, 2021)
2-177629453-G-A		not specified	Uncertain significance (Dec 21, 2022)
2-177629466-C-G			Likely benign (Dec 31, 2019)
2-177629484-G-A		not specified	Uncertain significance (May 26, 2023)
2-177629531-G-A		not specified	Uncertain significance (Oct 29, 2021)
2-177629531-G-T		Pigmented nodular adrenocortical disease, primary, 2	Uncertain significance (Apr 16, 2021)
2-177629556-C-T		PDE11A-related disorder	Conflicting classifications of pathogenicity (Jan 24, 2020)
2-177629562-C-T		Pigmented nodular adrenocortical disease, primary, 2 • PDE11A-related disorder	Benign/Likely benign (Jul 09, 2021)
2-177663872-C-A			Benign (Dec 31, 2019)
2-177663880-T-C			Benign/Likely benign (Dec 31, 2019)
2-177663894-A-G		Pigmented nodular adrenocortical disease, primary, 2	Uncertain significance (Oct 03, 2019)
2-177663901-C-G		not specified	Uncertain significance (Nov 17, 2023)
2-177663913-G-A		not specified	Uncertain significance (Feb 13, 2023)
2-177663913-G-C			Benign (Aug 20, 2020)
2-177663936-C-T		not specified	Uncertain significance (Oct 12, 2022)
2-177663975-C-T		Pigmented nodular adrenocortical disease, primary, 2	Benign (Sep 05, 2021)
2-177669524-C-G		not specified	Uncertain significance (Oct 12, 2021)
2-177669542-A-G		not specified	Uncertain significance (Apr 11, 2023)
2-177669596-A-G		Pigmented nodular adrenocortical disease, primary, 2	Benign (Sep 05, 2021)
2-177675473-C-T			Likely benign (Jun 14, 2018)
2-177675475-G-GT			Uncertain significance (Nov 16, 2022)
2-177675506-C-T		Pigmented nodular adrenocortical disease, primary, 2	Uncertain significance (May 15, 2023)
2-177675519-C-G			Likely benign (Dec 31, 2019)
2-177675565-A-G		Pigmented nodular adrenocortical disease, primary, 2	Benign (Sep 05, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE11A	protein_coding	protein_coding	ENST00000286063	20	485087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.69e-37	7.12e-7	122846	43	2859	125748	0.0116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.00401	515	515	1.00	0.0000292	6152
Missense in Polyphen		211	223.52	0.94398		2690
Synonymous	0.445	187	195	0.959	0.0000117	1772
Loss of Function	-0.723	52	46.7	1.11	0.00000252	550

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00745	0.00745
Ashkenazi Jewish	0.0113	0.0112
East Asian	0.00790	0.00791
Finnish	0.00292	0.00287
European (Non-Finnish)	0.00818	0.00810
Middle Eastern	0.00790	0.00791
South Asian	0.0518	0.0470
Other	0.00887	0.00818

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'- GMP, respectively. {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148}.
• Disease: DISEASE: Primary pigmented nodular adrenocortical disease 2 (PPNAD2) [MIM:610475]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269|PubMed:16767104}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cushing,s syndrome - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Hemostasis;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.506
• rvis_EVS: 0.76
• rvis_percentile_EVS: 86.86

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.528
• ghis: 0.414

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.726

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde11a
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: signal transduction;G protein-coupled receptor signaling pathway;metabolic process;negative regulation of cGMP-mediated signaling;negative regulation of cAMP-mediated signaling
• Cellular component: cellular_component;cytosol
• Molecular function: cyclic-nucleotide phosphodiesterase activity;3',5'-cyclic-nucleotide phosphodiesterase activity;3',5'-cyclic-AMP phosphodiesterase activity;cGMP-stimulated cyclic-nucleotide phosphodiesterase activity;cGMP binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity