NHLRC1

Chr 6AR

NHL repeat containing E3 ubiquitin protein ligase 1

Also known as: EPM2B, MALIN, MELF2, bA204B7.2

NCBI Gene: 378884 ENSG00000187566 UniProt: Q6VVB1 OMIM: 608072

This gene encodes an E3 ubiquitin-protein ligase that works with laforin phosphatase to clear toxic polyglucosan and protein aggregates through both the ubiquitin-proteasome system and autophagy pathways. Biallelic mutations cause Lafora disease (progressive myoclonic epilepsy type 2), a devastating autosomal recessive neurodegenerative disorder typically presenting in adolescence with progressive myoclonic epilepsy and cognitive decline.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Myoclonic epilepsy of Lafora 2MIM #620681

Clinical highlights

Gene-disease validity (ClinGen)

Lafora disease · ARDefinitivesufficient evidence for diagnostic panels

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)

—

P/LP submissions

—

P/LP missense

0.88

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — NHLRC1