DENND5B

Chr 12

DENN domain containing 5B

NCBI Gene: 160518 ENSG00000170456 UniProt: Q6ZUT9 OMIM: 617279

The protein functions as a guanine nucleotide exchange factor that activates RAB39A and RAB39B by promoting GDP to GTP exchange. Mutations cause autosomal recessive intellectual disability with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variation (pLI = 1.0, LOEUF = 0.155), indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in positive regulation of triglyceride transport. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADLimitednot for standalone diagnostic reporting

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

0.15

LOEUF· LoF intol.

LOF

Mechanism· G2P