PDE11A is the most recently discovered PDE enzyme family. In this family, only one gene, PDE11A, has been identified. It is a dual phosphodiesterase that hydrolyzes both cAMP and cGMP.

Four different isoforms of PDE11A (PDE11A1→A4) have been identified. The longest variant, PDE11A4 is composed of 20 coding exons of varying length, separated by introns, giving the gene a total length of 4441 bps.

PDE11A4 is a protein of 104 kDa: it contains two N-terminal GAF domains (between exons 3-12) and one C-terminal catalytic domain (between exons 14-22).

Isoform 1 is present in prostate, pituitary, heart, liver and skeletal muscle. Isoform 2 and 3 are expressed in the testis. Isoform 4 is the only isoform of the enzyme expressed in the adrenal cortex, where it is expressed substantially less than in the prostate.

Cytoplasm > cytosol.

PDE11A enzymes catalyze the hydrolysis of both cAMP and cGMP to 5-AMP and 5-GMP, respectively. This takes part in the down-regulation of the cAMP and cGMP signaling.
Inactive mutations of the isoform PDE11A4 gene have been identified in patients with adrenal Cushing syndrome due to micronodular adrenocortical hyperplasia. An association of PDE11A4 variants and other neoplasms is suggested since a higher frequency of PDE11A4 missense mutations is observed in patients with macronodular adrenal hyperplasia and testicular tumors than in the controls.

The catalytic domain is conserved among the 4 isoforms of PDE11A.
A high sequence similarity of 42-51% is found within the amino acid sequences of the catalytic regions of PDEs containing a Gaf sequence (i.e. PDE2A, PDE5A, PDE6B, PDE6C, PDE10A and PDE11A).
Gene conserved among species: Pan troglodytes: 98.6%; Canis lupus familiaris: 96.4%; Bos taurus: 95.9%; Mus musculus: 94.6%; Rattus norvegicus: 94.5%; Gallus gallus: 90%; Danio rerio: 90%.

Non sense.
Three PDE11A nonsense mutations leading to a premature stop codon were identified in 3 kindreds with adrenal Cushing syndrome due to micronodular adrenocortical hyperplasia.
Other missense mutations (genetic variants) are described in adrenocortical tumor, as macronodular adrenal hyperplasia (AIMAH), adrenocortical adenoma (ACA), adrenocortical carcinoma (ACC) and testicular tumors.

Loss of heterozygosity with loss of wild type allele have been reported in adrenocortical tumor (benign and malignant) with PDE11A4 missense mutations.