DENND3

Chr 8q24.3

DENN domain containing 3

Aliases:: KIAA0870
MANE:: ENST00000519811.6

OMIM: 617503 ↗NCBI: 22898 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

DENND3 · A2RUS2

v62025-08-01

Predicted Aligned Error matrix for DENND3 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

81.0/ 100

Confident

1,198 residues

Confidence breakdown

Very high(≥ 90)41%
Confident(70–90)41%
Low(50–70)7%
Very low(< 50)11%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Familial Hirschsprung Disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

hypothyroidism
0.40
liver disorder
0.30
Jaundice
0.28
Lower limb pain
0.27
color vision disorder
0.27
psoriatic arthritis
0.26
Oculomotor palsy
0.26
Alzheimer disease
0.25
placenta praevia
0.24
skull disorder
0.24

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

DENN domain-containing protein 3

Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity)