RNF19A

Chr 8

ring finger protein 19A, RBR E3 ubiquitin protein ligase

Also known as: RNF19

NCBI Gene: 25897 ENSG00000034677 UniProt: Q9NV58 OMIM: 607119

The protein functions as an E3 ubiquitin ligase that targets specific substrates including synphilin-1 and pathogenic SOD1 variants for proteasomal degradation. Mutations cause autosomal recessive spastic paraplegia, which primarily affects the corticospinal tracts leading to progressive lower limb spasticity and weakness. This gene is highly constrained against loss-of-function variants, suggesting that complete protein loss is not well tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the ring between ring fingers (RBR) protein family, and the encoded protein contains two RING-finger motifs and an in between RING fingers motif. This protein is an E3 ubiquitin ligase that is localized to Lewy bodies, and ubiquitylates synphilin-1, which is an interacting protein of alpha synuclein in neurons. The encoded protein may be involved in amyotrophic lateral sclerosis and Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

OMIM 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

0.47

LOEUF

Multiple*

Mechanism· predicted