The human caspase-9 gene contains 9 exons and 8 introns and was predicted to span over approximately 35 kb of the genomic DNA.

Three mRNA isoforms have been identified in Homo sapiens.
Caspase-9S, also classified as caspase-9b or caspase-9beta, is a small variant of caspase-9 lacking exons 3-6, which contain the catalytic domain. Caspase-9S functions as an endogenous dominant-negative isoform of full-length caspase-9 by binding to the Apaf-1 protein thus hampering its binding and processing of the full-length procaspase-9.
Recently, it has been cloned and characterized a novel caspase-9 splice variant, named caspase9-gamma. Caspase9-gamma is generated from an alternative splicing of the fourth exon of caspase-9 gene, that results in a 58 nucleotide-long insertion, absent in caspase-9 full length. As the inserted fragment introduces a stop codon, the resulting RNA sequence is prematurely terminated and translated in a 154 aminoacids protein corresponding to only the CARD domain of the caspase-9 full length. Caspase9-gamma does not contain small and large catalytic subunits and cannot promote apoptosis, but like caspase-S, it can function as an apoptosis inhibitor by interferring with the CARD-CARD interaction between procaspase-9 and Apaf-1.

Like for other caspase genes, caspase-9 mRNA is translated in a precursor protein, the procaspase, that is subsequently converted to the active enzyme. The procaspase-9 consists of 416 amino acids corresponding to a molecular weight of 46281 Da. Cleavages at Asp315 and Asp330 by granzyme B and CPP32 (caspase-3), respectively, generate two active peptides. The active caspase-9 is, in fact, constituted by an heterodimer of a 35kDa (p35) and a 10 kDa (p10) subunit. It belongs to the peptidase C14 family and contains three major domains: a prodomain (in which a CARD domain is located), a large subunit catalytic domain (LSCD) and a small subunit catalytic domain (SSCD).

Caspase-9 expression is ubiquitous, with highest expression in the heart and a moderate expression in liver, skeletal muscle, and pancreas.

Mainly cytosolic, but both proenzyme and active caspase-9 have been also observed in the mitochondria and in the nucleus.

Caspase-9 is a member of the cysteine aspartic acid protease, or caspase, family. The procaspase-9 is activated in apoptotic conditions and it is involved in the activation of the caspase cascade responsible for apoptosis execution. The procaspase-9 and Apaf-1 interact each other through their CARD domains generating, in presence of cytochrome c and ATP, the protein complex named "apoptosome". The latter one, in turn, cleaves and activates the effector caspases such the caspase-3.
Caspase-9 plays an essential role in apoptosis during normal development. The majority of homozygous CASP-9 null mice die perinatally with an enlarged and malformed cerebrum caused by a reduced apoptosis during brain development.

CASP9 (Canis familiaris, Pan troglodytes, Gallus gallus), Casp9 (Rattus norvegicus, Mus musculus), Casp9-A (Xenopous Laevis), Dr.16035 (Danio Rerio).

Not known in Homo sapiens

Three different somatic mutations have been detected in two colorectal carcinomas and in one gastric carcinoma among 353 cancer specimen analyzed, including 180 gastric, 104 colorectal and 69 lung adenocarcinomas. However, all these mutations were silent mutation, thus not contributing to the pathogenesis of these cancers.