UBQLN3

Summary

UBQLN3 (ubiquilin 3, HGNC:12510) is a protein-coding gene on chromosome 11p15.4, encoding Ubiquilin-3 (Q9H347).

This gene encodes a ubiquitin-like protein (ubiquilin) that shares a high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and are thus thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This gene is specifically expressed in the testis. It has been suggested that this gene may regulate cell-cycle progression during spermatogenesis, however, it has been shown that the ortholgous mouse gene is dispensable for embryonic development and spermatogenesis.

Source: NCBI Gene 50613 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_017481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12510
Approved symbol	UBQLN3
Name	ubiquilin 3
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	TUP-1
Ensembl gene	ENSG00000175520
Ensembl biotype	protein_coding
OMIM	605473
Entrez	50613

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000311659, ENST00000445998

RefSeq mRNA: 2 — MANE Select: NM_017481 NM_001347096, NM_017481

CCDS: CCDS7758

Canonical transcript exons

ENST00000311659 — 2 exons

Exon	Start	End
ENSE00001375996	5509874	5509957
ENSE00001376629	5507300	5509594

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 98.73.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3478 / max 312.6019, expressed in 10 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118374	0.3328	6
118373	0.0090	5
118375	0.0060	4

Top tissues by expression

226 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.73	gold quality
male germ cell	CL:0000015	97.18	gold quality
left testis	UBERON:0004533	97.17	gold quality
right testis	UBERON:0004534	96.80	gold quality
testis	UBERON:0000473	94.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.85	gold quality
adult organism	UBERON:0007023	88.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.66	gold quality
decidua	UBERON:0002450	56.55	gold quality
tibialis anterior	UBERON:0001385	56.53	silver quality
pancreatic ductal cell	CL:0002079	54.85	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
deltoid	UBERON:0001476	52.12	silver quality
epithelial cell of pancreas	CL:0000083	50.30	silver quality
quadriceps femoris	UBERON:0001377	49.54	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
thymus	UBERON:0002370	48.49	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
sural nerve	UBERON:0015488	48.16	silver quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.11
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting UBQLN3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-424-3P	97.20	65.86	385
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 3)

• Includes the identification of the ubiquilin 3 gene upstream of the beta-globin gene cluster and surrounding olfactory receptor genes. (PMID:11121057)
• Functional analysis of the orthologous mouse gene. (PMID:25776854)
• MicroRNA-targeting in spermatogenesis: Over-expressions of microRNA-23a/b-3p and its affected targeting of the genes ODF2 and UBQLN3 in spermatozoa of patients with oligoasthenozoospermia. (PMID:33784796)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ubqln3	ENSMUSG00000051618
rattus_norvegicus	Ubqln3	ENSRNOG00000023833
drosophila_melanogaster	CG31528	FBGN0051528

Paralogs (5): UBQLN1 (ENSG00000135018), UBL7 (ENSG00000138629), UBQLN4 (ENSG00000160803), UBQLNL (ENSG00000175518), UBQLN2 (ENSG00000188021)

Protein

Protein identifiers

Ubiquilin-3 — Q9H347 (reviewed: Q9H347)

All UniProt accessions (3): Q9H347, A0A140VJZ3, C9IYQ4

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Testis specific.

RefSeq proteins (2): NP_001334025, NP_059509* (*=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
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily

Pfam: PF00240, PF00627, PF23195

UniProt features (29 total): sequence variant 6, helix 6, compositionally biased region 5, strand 4, region of interest 4, domain 3, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1YQB	X-RAY DIFFRACTION	2
1WX7	SOLUTION NMR
2DAH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H347-F1	56.38	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2, YGACNNYACAR_UNKNOWN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, WEBER_METHYLATED_LCP_IN_FIBROBLAST_DN, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GNF2_CCNA1, ATF3_Q6, WEBER_METHYLATED_LCP_IN_SPERM_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, MARTENS_TRETINOIN_RESPONSE_UP

GO Biological Process (3): ubiquitin-dependent protein catabolic process (GO:0006511), cellular response to stress (GO:0033554), regulation of proteasomal protein catabolic process (GO:0061136)

GO Molecular Function (2): polyubiquitin modification-dependent protein binding (GO:0031593), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	1
modification-dependent protein catabolic process	1
response to stress	1
cellular response to stimulus	1
proteasomal protein catabolic process	1
regulation of protein catabolic process	1
modification-dependent protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBQLN3	TARDBP	Q13148	691
UBQLN3	CCNA1	P78396	550
UBQLN3	GARIN1B	Q96KD3	549
UBQLN3	SPATA3	Q8NHX4	540
UBQLN3	EPS15	P42566	518
UBQLN3	SPACA4	Q8TDM5	514
UBQLN3	OPTN	Q96CV9	504
UBQLN3	STIP1	P31948	496
UBQLN3	TRIM58	Q8NG06	493
UBQLN3	PSMD4	P55036	490
UBQLN3	HTT	P42858	478
UBQLN3	TMEM225	Q6GV28	474
UBQLN3	RAD23A	P54725	451
UBQLN3	SPATS1	Q496A3	438
UBQLN3	ADRM1	Q16186	415

IntAct

20 interactions, top by confidence:

A	B	Type	Score
UBQLN3	ASPA	psi-mi:“MI:0915”(physical association)	0.560
HEXB	UBQLN3	psi-mi:“MI:0915”(physical association)	0.560
NOS3	UBQLN3	psi-mi:“MI:0915”(physical association)	0.560
KLF11	UBQLN3	psi-mi:“MI:0915”(physical association)	0.560
NUP58	UBQLN3	psi-mi:“MI:0915”(physical association)	0.560
UBQLN3	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
EPS15	UBQLN3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (3): UBQLN3 (Protein-peptide), UBQLN3 (Positive Genetic), UBQLN3 (Affinity Capture-MS)

ESM2 similar proteins: A0A482PJY4, A2AH22, A3KPW9, A4IH17, A5D9M6, A7X5R6, A8Y4B2, D5LXJ0, E7FAG6, O22197, O42967, O74757, P0CH30, P38428, P46379, Q09463, Q0II22, Q15011, Q20798, Q2KIS3, Q3KPV4, Q5R5B0, Q68FU0, Q6DIP3, Q6IRP0, Q6MG49, Q6P135, Q6PA26, Q7T0Q3, Q7ZXQ3, Q8C5U9, Q8LPN7, Q8WUU8, Q91W67, Q91YL2, Q94AK4, Q96S82, Q9BV68, Q9C0C7, Q9C1X4

Diamond homologs: G5EFF7, P48510, Q14DL0, Q5R684, Q5XIP4, Q8C5U9, Q8R317, Q99NB8, Q9H347, Q9JJP9, Q9NIF3, Q9NRR5, Q9QZM0, Q9SII8, Q9SII9, Q9UHD9, Q9UMX0, Q8IYU4, P49633, Q54L35, A3KPW9, Q10169, O42967, A5D9M6, A7X5R6, B5X9S9, B5XFI8, C1BGZ8, C1BHN7, C1BXU5, C3KHF2, D5LXJ0, P0C032, P16709, P42739, P42740, P46379, P84589, Q05120, Q64339

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

188 predictions. Top by Δscore:

Variant	Effect	Δscore
11:5507594:CGA:C	donor_gain	0.9800
11:5509872:A:AC	donor_gain	0.8900
11:5509873:C:CC	donor_gain	0.8900
11:5509868:ACAT:A	donor_loss	0.8600
11:5509869:CATA:C	donor_loss	0.8600
11:5509870:AT:A	donor_loss	0.8600
11:5509871:TA:T	donor_loss	0.8600
11:5509872:ACC:A	donor_loss	0.8600
11:5509873:CCAGT:C	donor_gain	0.8100
11:5509592:CAG:C	acceptor_gain	0.8000
11:5509590:CACAG:C	acceptor_gain	0.7900
11:5509594:GCT:G	acceptor_gain	0.7800
11:5509865:TGTAC:T	donor_loss	0.7800
11:5508673:T:TA	donor_gain	0.7700
11:5509866:GTACA:G	donor_loss	0.7700
11:5509867:TACAT:T	donor_loss	0.7700
11:5509593:AGC:A	acceptor_gain	0.7600
11:5509595:C:A	acceptor_gain	0.7600
11:5509259:ATTGC:A	donor_gain	0.7500
11:5509259:ATTG:A	donor_gain	0.7400
11:5507593:A:AC	donor_gain	0.7300
11:5507594:C:CC	donor_gain	0.7300
11:5509591:ACAGC:A	acceptor_gain	0.7200
11:5509592:CAGCT:C	acceptor_gain	0.7200
11:5509596:T:A	acceptor_gain	0.7200
11:5508615:C:CT	donor_gain	0.7100
11:5508616:T:TT	donor_gain	0.7100
11:5509593:AGCT:A	acceptor_gain	0.6800
11:5509595:C:CC	acceptor_gain	0.6600
11:5507605:G:C	donor_gain	0.6500

AlphaMissense

4267 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:5509418:C:A	K47N	0.986
11:5509418:C:G	K47N	0.986
11:5507675:A:C	F628L	0.985
11:5507675:A:T	F628L	0.985
11:5507677:A:G	F628L	0.985
11:5509364:A:C	F65L	0.984
11:5509364:A:T	F65L	0.984
11:5509366:A:G	F65L	0.984
11:5509422:A:G	L46P	0.984
11:5507676:A:G	F628S	0.983
11:5509299:A:T	V87D	0.983
11:5507691:A:G	L623P	0.976
11:5509410:A:T	I50K	0.973
11:5507646:A:T	L638H	0.968
11:5509293:A:G	L89P	0.968
11:5509350:A:T	L70H	0.968
11:5509397:A:C	F54L	0.968
11:5509397:A:T	F54L	0.968
11:5509399:A:G	F54L	0.968
11:5509482:A:T	V26E	0.968
11:5509410:A:C	I50R	0.965
11:5507646:A:G	L638P	0.963
11:5507650:C:G	A637P	0.963
11:5509350:A:G	L70P	0.963
11:5509455:A:G	F35S	0.961
11:5509359:C:A	G67V	0.956
11:5509371:A:T	L63Q	0.956
11:5507657:A:C	N634K	0.955
11:5507657:A:T	N634K	0.955
11:5509454:G:C	F35L	0.955

dbSNP variants (sampled 300 via entrez): RS1000252841 (11:5510276 T>C), RS1000927466 (11:5511040 T>C), RS1001836136 (11:5510245 C>G,T), RS1002438801 (11:5511564 G>C,T), RS1003208400 (11:5507463 T>A), RS1003323464 (11:5507228 C>A,G), RS1003670493 (11:5507652 T>C), RS1004912754 (11:5510282 A>G), RS1005739416 (11:5509998 G>A), RS1005925955 (11:5511604 G>A,C), RS1007008206 (11:5511021 G>C), RS1007222732 (11:5506858 G>A), RS1008223662 (11:5508092 A>G), RS1008952832 (11:5506902 C>T), RS1010351139 (11:5510497 G>C)

Disease associations

OMIM: gene MIM:605473 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methotrexate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.