RSPO2

Chr 8AR

R-spondin 2

Also known as: CRISTIN2, HHRRD, TETAMS2

NCBI Gene: 340419 ENSG00000147655 UniProt: Q6UXX9 OMIM: 610575

The protein is a secreted ligand that activates canonical Wnt signaling by binding to LGR4-6 receptors and plays a crucial role in embryonic limb specification. Autosomal recessive mutations cause tetraamelia syndrome 2 (absence of all four limbs) and humerofemoral hypoplasia with radiotibial ray deficiency, representing severe limb malformation disorders. The gene shows tolerance to loss-of-function variants in the general population (low pLI), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the R-spondin family of proteins. These proteins are secreted ligands of leucine-rich repeat containing G protein-coupled receptors that enhance Wnt signaling through the inhibition of ubiquitin E3 ligases. A chromosomal translocation including this locus that results in the formation of a gene fusion has been identified in multiple human cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Humerofemoral hypoplasia with radiotibial ray deficiencyMIM #618022

Tetraamelia syndrome 2MIM #618021

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

LOF

Mechanism· G2P