DESI2

Chr 1

desumoylating isopeptidase 2

Also known as: C1orf121, CGI-146, DeSI-2, FAM152A, PNAS-4, PPPDE1

NCBI Gene: 51029 ENSG00000121644 UniProt: Q9BSY9 OMIM: 614638

The protein functions as a deubiquitinase that removes ubiquitin chains from target proteins and exhibits palmitoyl protein thioesterase activity that removes palmitoyl groups from proteins. Mutations cause autosomal recessive neurodegeneration with brain iron accumulation, typically presenting in childhood with progressive movement disorders and cognitive decline. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables deubiquitinase activity and long-chain fatty acyl-CoA hydrolase activity. Predicted to be involved in macromolecule depalmitoylation and proteolysis. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

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

0.45

LOEUF

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Mechanism