ARK2C

Chr 18

arkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C

This gene encodes an E3 ubiquitin-protein ligase that regulates motor axon elongation by enhancing BMP signaling through ubiquitination and degradation of SMAD inhibitors. Mutations cause autosomal recessive spinal muscular atrophy with congenital bone fractures, affecting both the neuromuscular system and skeletal development. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.32), indicating intolerance to protein-truncating mutations.

ResearchSummary from RefSeq, UniProt

E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation. Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.32

LOEUF· LoF intol.

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Mechanism

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