UBQLN2

Chr Xp11.21

ubiquilin 2

Aliases:: Chap1, Dsk2, RIHFB2157, LIC-2, CHAP1/DSK2
MANE:: ENST00000338222.7

OMIM: 300264 ↗NCBI: 29978 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

UBQLN2 · Q9UHD9

v62025-08-01

Predicted Aligned Error matrix for UBQLN2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

61.0/ 100

Low

624 residues

Confidence breakdown

Very high(≥ 90)3%
Confident(70–90)27%
Low(50–70)40%
Very low(< 50)30%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult onset neurodegenerative disorder
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Amyotrophic lateral sclerosis/motor neuron disease
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset dementia (encompassing fronto-temporal dementia and prion disease)
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Disease associations (Open Targets)

amyotrophic lateral sclerosis type 15
0.80
amyotrophic lateral sclerosis
0.64
familial amyotrophic lateral sclerosis
0.51
amyotrophic lateral sclerosis, dominant
0.37
hypertensive disorder
0.13
vascular dementia
0.11
frontotemporal dementia
0.11
Alzheimer disease
0.09
lung adenocarcinoma
0.08
neoplasm
0.08

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

Protein function (UniProt)

Ubiquilin-2

Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (PubMed:10983987). Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:18307982, PubMed:24215460). Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:19148225, PubMed:20529957). Negatively regulates the endocytosis of GPCR receptors: AVPR2 and ADRB2, by specifically reducing the rate at which receptor-arrestin complexes concentrate in clathrin-coated pits (CCPs) (PubMed:18199683)