5 exons spanning 967kb of genomic

Alternative splicing generates at least three transcript variants, their sizes are 1212bp, 1307 bp and 1068 bp

WISP3 contains four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. It has three isoforms: 1) variant 1, 354 aa, 39292 Da; 2) variant 2, 331 aa, This variant differs from variant 1 in two regions. It has an alternate 5 end which results in a different N-terminus. It also uses two alternative donor and acceptor sites in the middle coding region which result in a few internal aa differences between variant 1 and 2. 3) variant 3, 372 aa, This variant differs in the 5 UTR and CDS, compared to variant 1. The resulting protein is longer and has a distinct N-terminus, compared to variant 1.

Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine. Also expressed in skeletally-derived cells such as synoviocytes and articular cartilage chondrocytes.

Secreted (Probable).

It is a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family and may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is over-expressed in colon tumors. It is essential for normal postnatal skeletal growth and cartilage homeostasis. It acts as a putative growth regulator contributing to the inflammatory breast cancer by regulating tumor cell growth, invasion and angiogenesis.

Wnt1-inducible signaling proteins

Various types of mutations have been described, dispersed throughout the gene, including nucleotide substitutions, small deletions and small insertions. There are patients who are compound heterozygous, heterozygous or homozygous. The mutations cause progressive pseudorheumatoid dysplasia.

Somatic mutations that cause reading frameshifts at a polyadenosine tract within the WISP3 coding sequence have been observed at higher-than-expected rates in gastrointestinal tumors from patients with mutations in the mismatch repair pathway.