AP2S1

Chr 19q13.32

adaptor related protein complex 2 subunit sigma 1

Aliases:: FBHOk, FBH3
MANE:: ENST00000263270.11

OMIM: 602242 ↗NCBI: 1175 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

AP2S1 · P53680

v62025-08-01

Predicted Aligned Error matrix for AP2S1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

97.0/ 100

Very high

142 residues

Confidence breakdown

Very high(≥ 90)97%
Confident(70–90)4%
Low(50–70)0%
Very low(< 50)0%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial hyperparathyroidism or hypocalciuric hypercalcaemia
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Renal tubulopathies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Nephrocalcinosis or nephrolithiasis
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

familial hypocalciuric hypercalcemia 3
0.70
Familial hypocalciuric hypercalcemia type 3
0.68
neurodegenerative disease
0.55
HIV infectious disease
0.55
Alzheimer disease
0.48
multiple sclerosis
0.46
Parkinson disease
0.46
lysosomal storage disease
0.46
familial hypocalciuric hypercalcemia
0.38
dengue disease
0.37

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

Protein function (UniProt)

AP-2 complex subunit sigma

Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). May also play a role in extracellular calcium homeostasis