DENND5A

Chr 11AR

DENN domain containing 5A

Also known as: DEE49, EIEE49, RAB6IP1

NCBI Gene: 23258 ENSG00000184014 UniProt: Q6IQ26 OMIM: 617278

The protein functions as a guanine nucleotide exchange factor that activates Rab proteins by catalyzing GDP to GTP conversion and is recruited by RAB6 to Golgi membranes where it regulates membrane trafficking. Biallelic loss-of-function mutations cause developmental and epileptic encephalopathy 49, inherited in an autosomal recessive pattern. The pathogenic mechanism involves gain-of-function effects that disrupt normal Golgi-mediated cellular processes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a DENN-domain-containing protein that functions as a RAB-activating guanine nucleotide exchange factor (GEF). This protein catalyzes the conversion of GDP to GTP and thereby converts inactive GDP-bound Rab proteins into their active GTP-bound form. The encoded protein is recruited by RAB6 onto Golgi membranes and is therefore referred to as RAB6-interacting protein 1. This protein binds with RAB39 as well. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene are associated with early infantile epileptic encephalopathy-49. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 49MIM #617281

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.38

LOEUF

LOF

Mechanism· G2P