APPL1

Chr 3p14.3

adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1

Aliases:: APPL
MANE:: ENST00000288266.8

OMIM: 604299 ↗NCBI: 26060 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

APPL1 · Q9UKG1

v62025-08-01

Predicted Aligned Error matrix for APPL1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

80.4/ 100

Confident

709 residues

Confidence breakdown

Very high(≥ 90)53%
Confident(70–90)26%
Low(50–70)4%
Very low(< 50)17%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Familial diabetes
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic diabetes
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

MODY
0.64
neurodegenerative disease
0.29
atrial fibrillation
0.27
monogenic diabetes
0.15
Alzheimer disease
0.10
osteoporosis
0.10
neoplasm
0.09
placenta praevia
0.08
cancer
0.08
Huntington disease
0.07

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

Protein function (UniProt)

DCC-interacting protein 13-alpha

Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:10490823, PubMed:15016378, PubMed:19661063, PubMed:26073777, PubMed:26583432). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). Regulates TLR4 signaling in activated macrophages (By similarity). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (PubMed:19661063, PubMed:24879834, PubMed:26073777). Required for fibroblast migration through HGF cell signaling (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865)