MGRN1

Chr 16

mahogunin ring finger 1

Also known as: RNF156

NCBI Gene: 23295 ENSG00000102858 UniProt: O60291 OMIM: 607559

MGRN1 encodes an E3 ubiquitin-protein ligase that mediates protein monoubiquitination and regulates endosome-to-lysosome trafficking, while also inhibiting melanocortin receptor signaling and hedgehog pathway activity. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants, indicating that complete loss of MGRN1 function has significant developmental consequences.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein sequestering activity and ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; and protein monoubiquitination. Located in early endosome; nucleus; and plasma membrane. Is active in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

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

Mechanism· predicted