UBQLN2

Summary

UBQLN2 (ubiquilin 2, HGNC:12509) is a protein-coding gene on chromosome Xp11.21, encoding Ubiquilin-2 (Q9UHD9). 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.

This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases; and thus, are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein.

Source: NCBI Gene 29978 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 15 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 248 total — 3 pathogenic, 4 likely-pathogenic
• GTEx eGene: eQTL in 13 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 96
• MANE Select transcript: NM_013444
• Interaction hub: 2,370 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12509
Approved symbol	UBQLN2
Name	ubiquilin 2
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	Chap1, Dsk2, RIHFB2157, LIC-2, CHAP1/DSK2, PLIC-2, N4BP4, PLIC2
Ensembl gene	ENSG00000188021
Ensembl biotype	protein_coding
OMIM	300264
Entrez	29978

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000338222

ENST00000338222

RefSeq mRNA: 1 — MANE Select: NM_013444 NM_013444

CCDS: CCDS14374

Canonical transcript exons

ENST00000338222 — 1 exons

Exon	Start	End
ENSE00001368073	56563627	56567868

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.7432 / max 198.7226, expressed in 1807 samples.

Highest expression (Bgee): cerebellar vermis, pons, postcentral gyrus, parietal lobe, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

UBQLN2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	1.0e-37	-0.65	X:56599664:T:A
Brain Cerebellum	eqtl	2.7e-06	-0.15	X:57049373:C:T
Thyroid	eqtl	8.0e-06	-0.12	X:56638797:A:C
Brain Cerebellar Hemisphere	eqtl	1.1e-04	+0.16	X:56380409:T:C
Skin Sun Exposed Lower leg	eqtl	2.2e-04	-0.09	X:56349136:C:G
Colon Transverse	eqtl	1.5e-02	-0.48	X:56272592:A:G
Esophagus Gastroesophageal Junction	eqtl	1.8e-02	+0.08	X:56349136:C:G
Brain Caudate basal ganglia	eqtl	2.3e-02	-0.22	X:56079693:T:C
Whole Blood	eqtl	2.5e-02	+0.04	X:56638797:A:C
Skin Not Sun Exposed Suprapubic	eqtl	3.0e-02	+0.14	X:56431322:T:C
Brain Hypothalamus	eqtl	3.4e-02	+0.44	X:55571634:G:A
Brain Anterior cingulate cortex BA24	eqtl	4.4e-02	+0.38	X:55621778:C:T
Brain Nucleus accumbens basal ganglia	eqtl	4.9e-02	+0.13	X:56207188:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
196491	30.6592	1805
196492	2.0840	1231

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	98.17	gold quality
pons	UBERON:0000988	97.19	gold quality
postcentral gyrus	UBERON:0002581	97.17	gold quality
parietal lobe	UBERON:0001872	97.16	gold quality
endothelial cell	CL:0000115	97.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.91	gold quality
pigmented layer of retina	UBERON:0001782	96.89	gold quality
entorhinal cortex	UBERON:0002728	96.77	gold quality
superior vestibular nucleus	UBERON:0007227	96.53	gold quality
seminal vesicle	UBERON:0000998	96.49	gold quality
middle temporal gyrus	UBERON:0002771	96.45	gold quality
visceral pleura	UBERON:0002401	96.20	gold quality
dorsal root ganglion	UBERON:0000044	96.17	gold quality
parietal pleura	UBERON:0002400	96.13	gold quality
ventral tegmental area	UBERON:0002691	96.12	gold quality
superior frontal gyrus	UBERON:0002661	96.07	gold quality
urethra	UBERON:0000057	96.05	gold quality
pericardium	UBERON:0002407	96.04	gold quality
trigeminal ganglion	UBERON:0001675	95.94	gold quality
pleura	UBERON:0000977	95.93	gold quality
inferior vagus X ganglion	UBERON:0005363	95.93	gold quality
substantia nigra pars compacta	UBERON:0001965	95.90	gold quality
cranial nerve II	UBERON:0000941	95.77	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.71	gold quality
CA1 field of hippocampus	UBERON:0003881	95.60	gold quality
lower lobe of lung	UBERON:0008949	95.44	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.36	gold quality
subthalamic nucleus	UBERON:0001906	95.30	gold quality
occipital lobe	UBERON:0002021	95.30	gold quality
oral cavity	UBERON:0000167	95.14	gold quality
pylorus	UBERON:0001166	95.12	gold quality
medulla oblongata	UBERON:0001896	95.06	gold quality
orbitofrontal cortex	UBERON:0004167	95.04	gold quality
primary visual cortex	UBERON:0002436	94.97	gold quality
cauda epididymis	UBERON:0004360	94.91	gold quality
pharyngeal mucosa	UBERON:0000355	94.90	gold quality
penis	UBERON:0000989	94.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.82	gold quality
superior surface of tongue	UBERON:0007371	94.76	gold quality
nipple	UBERON:0002030	94.67	gold quality
lateral globus pallidus	UBERON:0002476	94.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.36	gold quality
synovial joint	UBERON:0002217	94.31	gold quality
caput epididymis	UBERON:0004358	94.31	gold quality
tongue	UBERON:0001723	94.26	gold quality
superficial temporal artery	UBERON:0001614	94.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.22	gold quality
saphenous vein	UBERON:0007318	94.16	gold quality
cortical plate	UBERON:0005343	94.12	gold quality
blood vessel layer	UBERON:0004797	94.10	gold quality
bronchial epithelial cell	CL:0002328	94.09	gold quality
corpus epididymis	UBERON:0004359	94.04	gold quality
body of tongue	UBERON:0011876	94.03	gold quality
globus pallidus	UBERON:0001875	93.94	gold quality
germinal epithelium of ovary	UBERON:0001304	93.91	gold quality
frontal pole	UBERON:0002795	93.90	gold quality
choroid plexus epithelium	UBERON:0003911	93.86	gold quality
tibia	UBERON:0000979	93.85	gold quality
biceps brachii	UBERON:0001507	93.61	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.61	gold quality
medial globus pallidus	UBERON:0002477	93.59	gold quality
jejunum	UBERON:0002115	93.51	gold quality
renal medulla	UBERON:0000362	93.49	gold quality
ganglionic eminence	UBERON:0004023	93.35	gold quality
prefrontal cortex	UBERON:0000451	93.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.05	gold quality
adult organism	UBERON:0007023	93.04	gold quality
temporal lobe	UBERON:0001871	93.01	gold quality
mammary duct	UBERON:0001765	92.96	gold quality
trabecular bone tissue	UBERON:0002483	92.95	gold quality
palpebral conjunctiva	UBERON:0001812	92.91	gold quality
gingiva	UBERON:0001828	92.89	gold quality
upper leg skin	UBERON:0004262	92.85	gold quality
paraflocculus	UBERON:0005351	92.82	gold quality
epithelium of mammary gland	UBERON:0003244	92.78	gold quality
skin of hip	UBERON:0001554	92.75	gold quality
jejunal mucosa	UBERON:0000399	92.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.69	gold quality
cerebral cortex	UBERON:0000956	92.63	gold quality
periodontal ligament	UBERON:0008266	92.61	gold quality
vena cava	UBERON:0004087	92.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.55	gold quality
mammalian vulva	UBERON:0000997	92.53	gold quality
Ammon’s horn	UBERON:0001954	92.51	gold quality
nucleus accumbens	UBERON:0001882	92.46	gold quality
telencephalon	UBERON:0001893	92.38	gold quality
heart right ventricle	UBERON:0002080	92.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.36	gold quality
gingival epithelium	UBERON:0001949	92.34	gold quality
frontal cortex	UBERON:0001870	92.20	gold quality
neocortex	UBERON:0001950	92.06	gold quality
esophagus squamous epithelium	UBERON:0006920	91.99	gold quality
middle frontal gyrus	UBERON:0002702	91.93	gold quality
islet of Langerhans	UBERON:0000006	91.92	gold quality
tongue squamous epithelium	UBERON:0006919	91.89	gold quality
forebrain	UBERON:0001890	91.83	gold quality
thymus	UBERON:0002370	91.83	gold quality
epithelium of esophagus	UBERON:0001976	91.82	gold quality
embryo	UBERON:0000922	91.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-36552	no	118.49
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	133.6
Putamen	tissue	132.7
Cerebral cortex	tissue	131.7	high
Somatosensory cortex	tissue	131.7
Hippocampal formation	tissue	130.5
Basal ganglia	tissue	127.1	high
Occipital cortex	tissue	124.4
Motor cortex	tissue	120.1
Prefrontal cortex	tissue	119.9
Cerebellum	tissue	118.3	high
Ventral forebrain	tissue	115.0
Thalamus	tissue	110.9
Septum	tissue	110.8
Retrosplenial and cingulate cortex	tissue	109.9
Frontal cortex	tissue	109.2
Temporal cortex	tissue	109.2
Entorhinal cortex	tissue	108.6
Midbrain	tissue	104.4
Pons	tissue	103.3
Superior colliculi	tissue	102.4
Hypothalamus	tissue	102.0
Retrosplenial cortex	tissue	98.3
Insular cortex	tissue	97.4
Olfactory bulb	tissue	96.9
Amygdala	tissue	89.1
Medulla oblongata	tissue	88.7
Substantia nigra	tissue	88.3
Periaqueductal gray	tissue	84.4
Spinal cord	tissue	82.6
Corpus callosum	tissue	77.5
Nucleus accumbens	tissue	63.0
Postcentral gyrus	tissue	57.6
Locus coeruleus	tissue	54.5
Hippocampus	tissue	50.2	high
Choroid plexus	tissue	34.0
Skeletal muscle	tissue	26.3	low
Parathyroid gland	tissue	22.2	high
Tongue	tissue	21.2
Retina	tissue	20.6
Ovary	tissue	20.5	medium
Heart muscle	tissue	20.2	medium
Thyroid gland	tissue	19.4	medium
Prostate	tissue	19.0	high
Adrenal gland	tissue	19.0	medium
Seminal vesicle	tissue	18.8
Liver	tissue	18.1	medium
Thymus	tissue	17.6
Urinary bladder	tissue	17.4	medium
Tonsil	tissue	17.4	high
Lymph node	tissue	17.2	high
Smooth muscle	tissue	17.2	medium
Esophagus	tissue	16.6	high
Fallopian tube	tissue	16.5	medium
Endometrium 1	tissue	15.5	medium
Pituitary gland	tissue	15.2
Epididymis	tissue	15.1	medium
Cervix	tissue	15.0
Placenta	tissue	14.9	high
Spleen	tissue	14.1	medium
Appendix	tissue	14.0	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (130.5), Ventral hippocampus (122.2), Subiculum (121.8), Dorsal spinal cord (82.6), Ventral spinal cord (77.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting UBQLN2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 134 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548A-5P	99.94	71.27	3482

Functional genomics

Regional missense constraint (gnomAD)

ENST00000338222 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
X:56,563,874–56,563,959	39 / 27.6	1.41	no
X:56,563,960–56,564,717	129 / 198.1	0.65	no
X:56,564,718–56,565,745	278 / 279.4	1.00	no

Literature-anchored findings (GeneRIF, showing 40)

• solution structure of the ubl domain of hPLIC-2 (PMID:11827521)
• hPLIC-2 interferes with the ubiquitin-mediated proteolysis of p53 and interacts with proteasomes (PMID:12972570)
• knockdown of ubiquilin-1 and -2 protein expression by RNAi (RNA interference) increased Pen-2 and nicastrin levels (PMID:15975090)
• Ubiquilin is capable of forming dimers. Dimerization requires the central region of ubiquilin, but not its UBL or the UBA domains. Monomeric ubiquilin is likely to be the active form that is involved in binding presenilin proteins. (PMID:16813565)
• hHR23a and hPLIC2 interact via UBL/UBA domain interactions (PMID:17098253)
• Ubiquitin-like protein PLIC-2 is identified as a negative regulator of G protein-coupled receptor endocytosis. (PMID:18199683)
• siRNA-mediated UBQLN2 depletion made cells more susceptible to starvation-induced cell death. UBQLN2 regulates cell survival during starvation. (PMID:19148225)
• findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention (PMID:21857683)
• The results of this study suggested that UBQLN2 gene mutations are rare in French amyotrophic lateral sclerosis. (PMID:22169395)
• Found a pathophysiological link between C9ORF72 expansions and ubiquilin-2 (UBQLN) proteins in amyotrophic lateral sclerosis and frontotemporal lobar degeneration that is associated with a highly characteristic pattern of UBQLN pathology. (PMID:22426854)
• The results of this study support support a causative role of the UBQLN2 gene in the pathogenesis of ALS and suggest that UBQLN2 mutations are rare in the French and French-Canadian population. (PMID:22560112)
• The results of this study suggested that UBQLN2 was not found to be a cause of familial ALS in the Netherlands. (PMID:22676852)
• A novel missense UBQLN2 mutation (c.1460C>T, p.T487I) was identified in 2 apparently unrelated multigenerational amyotrophic lateral sclerosis families with no evidence of frontotemporal dementia. This mutation segregated with the disease. (PMID:22717235)
• No causative mutations within the PXX domain of the UBQLN2 gene are found in familial frontotemoral dementia patients. (PMID:22729385)
• This study reported 3 novel UBQLN2 mutations, accounting for 1.2% (2/161) ALS and 2.2% (1/45) FTD patients, including a patient with pure FTD. (PMID:22892309)
• data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD. (PMID:23138764)
• Genetic variations in UBQLN2 in a predominantly Flanders-Belgian cohort of frontotemporal lobar degeneration patients are extremely rare. (PMID:23312802)
• The 4-aminoquinolines were competitive inhibitors of UBQLN2 binding to TDP-43. (PMID:23541532)
• Its mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients. (PMID:23582661)
• results were confirmed by similar findings for ubiquilin-1 and -2 in human brain tissue sections, where accumulation was observed in huntingtin inclusions (PMID:23774650)
• The P506S mutation in UBQLN2 can affect both males and females with frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). (PMID:23944734)
• Its mutations are not frequent cause of amyotrophic lateral sclerosis in Ireland. (PMID:23973441)
• The dtat of study suggest that UBQLN2 is generally involved in the pathogenesis of ALS. (PMID:24085347)
• no evidence for involvement of ubiquilin 2 in tau pathology (PMID:24086754)
• Causative mutation in the UBQLN2 gene is rare in Korean patients with either familial or sporadic ALS. (PMID:24684794)
• As ubiquilin-2-positive inclusions are identified in brain, this mutant peptide predisposes to protein misfolding and accumulation. (PMID:24771548)
• A single putative mutation of UBQLN2 in a cohort of patients with front temporal lobar degeneration was found. (PMID:25179229)
• Data indicate cognitive deficits in mutant ubiquilin 2 protein UBQLN2P497H transgenic mice. (PMID:25246588)
• ALS-linked mutations in both OPTN and UBQLN2 interfere with the constitution of specific endosomal vesicles, suggesting that the vesicles are involved in protein homeostasis and that these proteins function in common pathological processes. (PMID:25398946)
• ALS-linked mutations in ubiquilin-2 or hnRNPA1 reduce interaction between ubiquilin-2 and hnRNPA1 (PMID:25616961)
• UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma. (PMID:25672654)
• Mutations in UBQLN2 gene cause dominant inheritance of amyotrophic lateral sclerosis due to Defective Proteasome Delivery. (PMID:26075709)
• Results showed that UBQLN2 is selectively recruited to nuclear inclusions in Huntington’s disease but not spinocerebellar ataxia type 3 (PMID:26141599)
• UBQLN2 is specifically expressed in the urine of urothelial carcinoma patients. (PMID:26303000)
• These findings provide a molecular basis for the development of ALS/FTD-associated proteinopathy and establish novel therapeutic targets for ALS. (PMID:26944018)
• Frontotemporal dementia -linked mutations in gene ubiquilin 2 encoding autophagy adaptor proteins , indicate that impaired autophagy might cause Frontotemporal dementia. (PMID:27166223)
• Ubiquilin-2 immunostaining - a new marker as a diagnostic supplement in urine cytology? (PMID:27168037)
• Ubiquilins are a family of chaperones for cytosolically exposed transmembrane domains and use ubiquitin to triage clients for degradation via coordinated intra- and intermolecular interactions. (PMID:27345149)
• The structures of proteasome substrate receptor complexes with the shuttle factors that deliver ubiquitinated proteins to proteasomes have been solved, namely human Rpn13 complexed with PLIC2 and Saccharomyces cerevisiae Rpn1 with Rad23. (PMID:27396824)
• excess UBQLN2 is toxic rather than protective to neurons and that uncontrolled enhancement of UBQLN2 function is involved in UBQLN2 pathogenesis (PMID:27456931)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ubqln2	ENSMUSG00000050148
rattus_norvegicus	Ubqln2	ENSRNOG00000003099
drosophila_melanogaster	CG31528	FBGN0051528

Paralogs (5): UBQLN1 (ENSG00000135018), UBL7 (ENSG00000138629), UBQLN4 (ENSG00000160803), UBQLNL (ENSG00000175518), UBQLN3 (ENSG00000175520)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R684	99.8%	Diamond
Arabidopsis thaliana	Q9SII8	85.6%	Diamond
Saccharomyces cerevisiae S288C	P48510	52.1%	Diamond
Dictyostelium discoideum	Q9NIF3	52.1%	Diamond
Danio rerio	A3KPW9	49.1%	Diamond
Caenorhabditis elegans	G5EFF7	34.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KLF8	protein-coding	11279
RRAGB	protein-coding	10325
SPIN3	protein-coding	169981
NBDY	protein-coding	550643

Protein

Protein identifiers

Ubiquilin-2 — Q9UHD9 (reviewed: Q9UHD9)

Alternative names: Chap1, DSK2 homolog, Protein linking IAP with cytoskeleton 2, Ubiquitin-like product Chap1/Dsk2

All UniProt accessions (1): Q9UHD9

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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. 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. 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).

Subunit / interactions. Homodimer. Forms heterodimer with UBQLN1. Binds UBE3A and BTRC. Interacts with the 19S proteasome subunit. Interacts with C9orf72. Interacts with HNRNPA1 and HNRNPU. Found in a complex with UBQLN1 and MAP1LC3A/B/C. Interacts with EPS15, EPN1 and EPN2. Interacts with HERPUD1. Interacts with RAD23A. Interacts with TARDBP. Interacts (via C-terminus) with FAF2 (via N-terminus). Interacts with UBQLN4. Binds CD47.

Subcellular location. Cytoplasm. Nucleus. Membrane. Cytoplasmic vesicle. Autophagosome.

Post-translational modifications. Degraded during macroautophagy.

Disease relevance. Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (ALS15) [MIM:300857] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ubiquitin-like domain is essential for its inhibitory effect on GPCR endocytosis. Mediates its association with the subunits of the proteasome. The UBA domain is essential for its association with microtubule-associated protein 1 light chain 3 (MAP1LC3). Mediates its association with ubiquitinated substrates. Dimerization is dependent upon the central region of the protein containing the STI1 domains and is independent of its ubiquitin-like and UBA domains.

Induction. Highly expressed in mitotic cells from metaphase to telophase. Expression in non-mitotic cells is very low.

RefSeq proteins (1): NP_038472* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR006636	STI1_HS-bd	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR015496	Ubiquilin	Family
IPR015940	UBA	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily

Pfam: PF00240, PF00627, PF23195

UniProt features (58 total): repeat 12, sequence variant 12, compositionally biased region 7, domain 6, strand 6, region of interest 5, helix 5, initiator methionine 1, chain 1, modified residue 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
1J8C	Solution Structure of the Ubiquitin-like Domain of hPLIC-2	SOLUTION NMR
2NBV	Solution structure of the Rpn13 Pru domain engaging the hPLIC2 UBL domain	SOLUTION NMR
6MUN	Structure of hRpn10 bound to UBQLN2 UBL	SOLUTION NMR
7F7X	Protein complex between phosphorylated ubiquitin and Ubqln2 UBA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHD9-F1	62.24	0.03

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
N-acetylalanine	2

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 303 (showing top): GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_VACUOLE_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, TTTGTAG_MIR520D, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, CREBP1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION

GO Biological Process (10): autophagosome assembly (GO:0000045), ubiquitin-dependent protein catabolic process (GO:0006511), regulation of macroautophagy (GO:0016241), ERAD pathway (GO:0036503), negative regulation of clathrin-dependent endocytosis (GO:1900186), negative regulation of G protein-coupled receptor internalization (GO:1904021), positive regulation of ERAD pathway (GO:1904294), regulation of autophagosome assembly (GO:2000785), autophagy (GO:0006914), negative regulation of transport (GO:0051051)

GO Molecular Function (4): polyubiquitin modification-dependent protein binding (GO:0031593), identical protein binding (GO:0042802), molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), autophagosome (GO:0005776), cytosol (GO:0005829), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Clathrin-mediated endocytosis	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

43 GO namespaces:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
regulation of autophagy	1
macroautophagy	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
negative regulation of receptor-mediated endocytosis	1
clathrin-dependent endocytosis	1
regulation of clathrin-dependent endocytosis	1
G protein-coupled receptor internalization	1
negative regulation of receptor internalization	1
regulation of G protein-coupled receptor internalization	1
ERAD pathway	1
positive regulation of proteasomal protein catabolic process	1
regulation of ERAD pathway	1
positive regulation of response to endoplasmic reticulum stress	1
autophagosome assembly	1
regulation of vacuole organization	1
regulation of organelle assembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
transport	1
negative regulation of biological process	1
regulation of transport	1
modification-dependent protein binding	1
protein binding	1
protein-macromolecule adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
vacuole	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
ERAD pathway	BP	mutant phenotype
negative regulation of G protein-coupled receptor internalization	BP	mutant phenotype
negative regulation of clathrin-dependent endocytosis	BP	mutant phenotype
positive regulation of ERAD pathway	BP	mutant phenotype
regulation of autophagosome assembly	BP	mutant phenotype
regulation of macroautophagy	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
identical protein binding	MF	physical interaction
molecular condensate scaffold activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,370 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBQLN2	C9orf72	Q96LT7	857
UBQLN2	HSPA13	P48723	825
UBQLN2	UBL7	Q96S82	824
UBQLN2	VCP	P55072	819
UBQLN2	TARDBP	Q13148	805
UBQLN2	FUS	P35637	799
UBQLN2	ATXN2	Q99700	778
UBQLN2	STIP1	P31948	777
UBQLN2	OPTN	Q96CV9	773
UBQLN2	PSMD4	P55036	751
UBQLN2	CHMP2B	Q9UQN3	750
UBQLN2	SOD1	P00441	741
UBQLN2	A0A087WTZ4	A0A087WTZ4	724
UBQLN2	ALS2	Q96Q42	719
UBQLN2	DDI1	Q8WTU0	719

IntAct

Human interaction partners of UBQLN2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 251 partners by confidence:

Partner	Interaction type	MIscore	Records
RAD23A	physical association	0.710	6
ADRM1	direct interaction	0.710	4
C1QA	physical association	0.670	6
HSPA13	physical association	0.670	6
RNF11	physical association	0.670	4
VENTX	physical association	0.670	3
HNRNPA1	physical association	0.590	6
HTT	physical association	0.560	12
C6orf15	physical association	0.560	8
AGR3	physical association	0.560	6
CLPSL2	physical association	0.560	6
CSN2	physical association	0.560	6
DEFA6	physical association	0.560	6
GALP	physical association	0.560	6
PRAP1	physical association	0.560	6
PRR4	physical association	0.560	6
PTGDS	physical association	0.560	6
RNF208	physical association	0.560	6
SFTPA2	physical association	0.560	6
WFDC12	physical association	0.560	6
ZG16B	physical association	0.560	6
AGR2	physical association	0.560	5
C1QC	physical association	0.560	5
CEACAM6	physical association	0.560	5
COL1A2	physical association	0.560	5
CSTF2	physical association	0.560	5
CSTF2T	physical association	0.560	5
DDR1	physical association	0.560	5
DESI1	physical association	0.560	5
DUSP21	physical association	0.560	5

BioGRID (979 interactions; top human partners by supporting records in a sample of 600 records): UBC (Affinity Capture-Western; 7 records), HNRNPU (Two-hybrid; 4 records), ATP6V1G1 (Affinity Capture-Western; 3 records), FUS (Affinity Capture-MS; 3 records), HNRNPA1 (Two-hybrid; 3 records), HSPA13 (Affinity Capture-MS; 3 records), HSPA1A (Affinity Capture-MS; 3 records), HSPA8 (Affinity Capture-MS; 3 records), PSMD4 (Affinity Capture-MS; 3 records), ADRM1 (Reconstituted Complex; 2 records), ALDH3A2 (Affinity Capture-MS; 2 records), AZGP1 (Affinity Capture-MS; 2 records), BAG6 (Affinity Capture-MS; 2 records), COL1A2 (Affinity Capture-MS; 2 records), CSTF2 (Two-hybrid; 2 records)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
UBQLN2	“down-regulates quantity by destabilization”	TARDBP	binding
UBQLN2	up-regulates	Stress_granules
UBQLN2	down-regulates	Unfolded_Proteins
UBQLN2	“up-regulates quantity by stabilization”	HNRNPA1	binding
UBQLN2	“up-regulates quantity by stabilization”	HNRNPU	binding
UBQLN2	“up-regulates quantity by stabilization”	HNRNPA3	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ Ubiquilin-proteasome complex	6	UBQLN2, PSMA1, PSMA2, PSMA6, UBE3A, UBQLN1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 251 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
InlB-mediated entry of Listeria monocytogenes into host cell	6	28.0×	8e-06
Regulation of innate immune responses to cytosolic DNA	5	23.4×	8e-05
Stabilization of p53	5	23.4×	8e-05
Negative regulation of MET activity	6	19.1×	5e-05
TICAM1, RIP1-mediated IKK complex recruitment	5	18.4×	2e-04
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	5	15.9×	3e-04
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	6	15.6×	9e-05
activated TAK1 mediates p38 MAPK activation	5	15.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cell-substrate adhesion	8	17.8×	1e-05
complement activation, classical pathway	6	14.6×	9e-04
antibacterial humoral response	7	10.4×	1e-03
antimicrobial humoral immune response mediated by antimicrobial peptide	11	8.0×	8e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	15	3.5×	6e-03

Disease & clinical

Genetic variants

Variant evidence for UBQLN2: 248 ClinVar records (7 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

248 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	158
Likely benign	54
Benign	8

Top pathogenic / likely-pathogenic (7)

Showing all 7 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
29950	NM_013444.4(UBQLN2):c.1490C>A (p.Pro497His)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
29951	NM_013444.4(UBQLN2):c.1489C>T (p.Pro497Ser)	Pathogenic	criteria provided, single submitter	2
29952	NM_013444.4(UBQLN2):c.1516C>A (p.Pro506Thr)	Pathogenic	criteria provided, single submitter	2
157594	NM_013444.4(UBQLN2):c.1490C>T (p.Pro497Leu)	Likely pathogenic	criteria provided, single submitter	2
1175827	NM_013444.4(UBQLN2):c.1174A>G (p.Met392Val)	Likely pathogenic	criteria provided, single submitter	1
2630374	NM_013444.4(UBQLN2):c.1517C>T (p.Pro506Leu)	Likely pathogenic	criteria provided, single submitter	1
3336842	NM_013444.4(UBQLN2):c.1663C>T (p.Pro555Ser)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore UBQLN2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 15 predictions of 21):

Position(s)	Effect	Δscore	Sites
X:56563741–56563742	donor_loss	0.4200	5
X:56563742	donor_loss	0.4100
X:56563740	donor_loss	0.3900	2
X:56563743	donor_loss	0.3900
X:56563740	donor_loss	0.3800
X:56563743	donor_loss	0.3700
X:56563739	donor_loss	0.3300
X:56563739	donor_loss	0.3200
X:56563743	donor_loss	0.3100
X:56563718	donor_loss	0.3000

AlphaMissense

1,857 missense substitutions predicted likely pathogenic (of 4,124 scored), across 430 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M592	9	0.979	0.999
F594	8	0.998	1.000
H99	8	0.988	1.000
D252	8	0.987	0.998
F76	8	0.982	1.000
N312	8	0.976	0.997
F65	8	0.971	0.999
F57	8	0.970	0.999
N600	8	0.970	0.999
D610	8	0.961	0.996
N318	8	0.957	0.999
D83	8	0.949	0.996
F292	8	0.932	0.995
F46	8	0.916	0.999
N240	8	0.901	0.994
F433	8	0.900	0.996
D85	8	0.861	0.972
D274	8	0.861	0.988
H90	8	0.855	0.989
F364	8	0.855	0.956

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000219
Breast Invasive Carcinoma (TCGA)	unfavorable	0.00091

Disease associations

OMIM: gene MIM:300264 | disease phenotypes: MIM:300857

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
amyotrophic lateral sclerosis type 15	Definitive	X-linked	4
amyotrophic lateral sclerosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 15	Definitive	XL

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Adult-onset neurological disorders	green
Amyotrophic lateral sclerosis/motor neuron disease	green
Early onset dementia (encompassing fronto-temporal dementia and prion disease)	green
Neurodegenerative disorders, adult onset	green

Mondo (2): amyotrophic lateral sclerosis type 15 (MONDO:0010459), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

showing 60 of 96 phenotypes (HPO-id order):

HPO	Term
HP:0000020	Urinary incontinence
HP:0000217	Xerostomia
HP:0000252	Microcephaly
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001308	Tongue fasciculations
HP:0001317	Abnormal cerebellum morphology
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001423	X-linked dominant inheritance
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002061	Lower limb spasticity
HP:0002072	Chorea
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002167	Abnormal speech pattern
HP:0002169	Clonus
HP:0002171	Gliosis
HP:0002179	Opisthotonus
HP:0002180	Neurodegeneration
HP:0002305	Athetosis
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002425	Anarthria
HP:0002460	Distal muscle weakness
HP:0002463	Language impairment
HP:0002483	Bulbar signs
HP:0002530	Axial dystonia
HP:0002540	Inability to walk
HP:0002544	Retrocollis
HP:0002599	Head titubation
HP:0002650	Scoliosis
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003324	Generalized muscle weakness
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003429	CNS hypomyelination
HP:0003447	Axonal loss
HP:0003470	Paralysis
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067354 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
resorcinol	increases expression	1
M-VAC protocol	increases response to substance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	affects expression	1
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652759	Binding	Binding affinity to human UBQLN2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

4 cell lines: 2 induced pluripotent stem cell, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E7N1	KOLF2.1J UBQLN2 P497H SNV/Y	Induced pluripotent stem cell	Male
CVCL_E7N3	KOLF2.1J UBQLN2 P506T SNV/Y	Induced pluripotent stem cell	Male
CVCL_TW09	HAP1 UBQLN2 (-) 1	Cancer cell line	Male
CVCL_TW10	HAP1 UBQLN2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 390 trials:

NCT	Phase	Status	Title
NCT00542412	Phase 4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	Phase 4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	Phase 4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	Phase 4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	Phase 4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00165763	Phase 4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	Phase 4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	Phase 4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	Phase 4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00021697	Phase 3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	Phase 3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	Phase 3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	Phase 3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	Phase 3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	Phase 3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	Phase 3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	Phase 3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	Phase 3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	Phase 3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	Phase 3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	Phase 3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	Phase 3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	Phase 3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	Phase 3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	Phase 3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	Phase 3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	Phase 3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	Phase 3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	Phase 3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	Phase 3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	Phase 3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	Phase 3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	Phase 3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	Phase 3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	Phase 3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	Phase 3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	Phase 3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	Phase 3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	Phase 3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	Phase 3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	Phase 3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04577404	Phase 3	COMPLETED	Safety Extension Study of Oral Edaravone Administered in Subjects With Amyotrophic Lateral Sclerosis (ALS)
NCT04745299	Phase 3	COMPLETED	Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS
NCT04768972	Phase 3	ACTIVE_NOT_RECRUITING	FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
NCT04944784	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT05021536	Phase 3	UNKNOWN	Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
NCT05151471	Phase 3	TERMINATED	Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS
NCT05178810	Phase 3	COMPLETED	Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
NCT05193994	Phase 3	TERMINATED	Triumeq in Amyotrophic Lateral Sclerosis
NCT05442775	Phase 3	TERMINATED	A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
NCT05568615	Phase 3	COMPLETED	Extension Study Following the Studies MT-1186-A03 or A04 to Evaluate the Safety of Oral Edaravone in Subjects With ALS
NCT05619783	Phase 3	COMPLETED	Extension Study Evaluating The Safety And Tolerability of AMX0035
NCT05753852	Phase 3	UNKNOWN	Open Label Extension of TUDCA-ALS Study
NCT05866926	Phase 3	TERMINATED	Study to Investigate the Long-term Safety of FAB122 in Patients With Amyotrophic Lateral Sclerosis
NCT06008249	Phase 3	TERMINATED	Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)
NCT06658977	Phase 3	TERMINATED	RolloverTreatment With Triumeq for People With ALS Following the Lighthouse II Trial
NCT06973629	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for UBQLN2 across ~30M SureChEMBL compounds — explore on Sugi Predict.