GeneBe

PDE11A

protein-coding

phosphodiesterase 11A, the group of Phosphodiesterases

Gene summary

The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016953.4

Inheritance

AD

ClinVar variants

P:13U:173B:58

Top phenotype

Pigmented nodular adrenocortical disease, primary, 2

gnomAD constraint

pLI —, LoF o/e 1.11

Max pathogenic AF

—

Genomic locus

chr2:177,623,244-178,108,339

External References & Databases

Ensembl (ENSG00000128655)NCBI Gene (50940)OMIM (604961)HGNC:8773GenCCUniProt (Q9HCR9)AlphaFoldClinVar (PDE11A)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~485.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pigmented nodular adrenocortical disease, primary, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012505

Submitter: PanelApp Australia

pigmented nodular adrenocortical disease, primary, 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012505

Submitter: Genomics England PanelApp

pigmented nodular adrenocortical disease, primary, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012505

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Pigmented nodular adrenocortical disease, primary, 2AD

Manifestation: Endocrine

Intervention: Endocrine

Rationale: Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial

Refs: 16767104; 20351491; 21115159Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDE11A variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 155
not providedTotal: 82
Pigmented nodular adrenocortical disease, primary, 2Total: 38
PDE11A-related disorderTotal: 30
Bardet-Biedl syndrome 16Total: 1
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016953.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
31
clinvar
6
clinvar
 38
missense
149
clinvar
12
clinvar
6
clinvar
 167
nonsense
5
clinvar
8
clinvar
 13
start loss
0
frameshift
7
clinvar
9
clinvar
2
clinvar
 18
splice donor/acceptor (+/-2bp)
1
clinvar
6
clinvar
1
clinvar
 8
Total0131734612244

Highest pathogenic variant AF is 0.00007252108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_016953.4RefSeqNP_058649.320MANE Select
ENST00000286063.11EnsemblENSP00000286063.520MANE Select
NM_001077196.2RefSeqNP_001070664.116Standard
NM_001077197.2RefSeqNP_001070665.120Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cushing,s syndrome - Homo sapiens (human)
  • Purine metabolism - Homo sapiens (human)
  • Morphine addiction - Homo sapiens (human)
  • Phosphodiesterases in neuronal function
  • Signaling by GPCR

Biological Process

  • signal transduction
  • G protein-coupled receptor signaling pathway
  • metabolic process
  • negative regulation of cGMP-mediated signaling
  • negative regulation of cAMP-mediated signaling

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

Cellular Component

  • cellular_component
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000286063
Coding exons
20
Length
485087
Individuals with no LoFs
122846
Homozygous LoFs
43
Heterozygous LoFs
2859
Defined
125748
p
0.0116
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.004015155151.000.00002926152
Missense (PolyPhen)211223.520.943982690
Synonymous0.4451871950.9590.00001171772
Loss of Function-0.7235246.71.110.00000252550

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00260.0026notable
Latino/Admixed American0.00490.0048notable
Ashkenazi Jewish0.0110.011notable
East Asian0.00790.0079notable
Finnish0.00290.0029notable
European (Non-Finnish)0.00820.0081notable
South Asian0.0520.047notable
Other0.00890.0082notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.141

Intolerance Scores

LoFtool
0.506
RVIS EVS
0.76
RVIS percentile EVS
86.86

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.726

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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