UBL3

Summary

UBL3 (ubiquitin like 3, HGNC:12504) is a protein-coding gene on chromosome 13q12.3, encoding Ubiquitin-like protein 3 (O95164).

Located in extracellular exosome.

Source: NCBI Gene 5412 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_007106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12504
Approved symbol	UBL3
Name	ubiquitin like 3
Location	13q12.3
Locus type	gene with protein product
Status	Approved
Aliases	HCG-1, DKFZP434K151, FLJ32018
Ensembl gene	ENSG00000122042
Ensembl biotype	protein_coding
OMIM	604711
Entrez	5412

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380680

RefSeq mRNA: 1 — MANE Select: NM_007106 NM_007106

CCDS: CCDS9334

Canonical transcript exons

ENST00000380680 — 5 exons

Exon	Start	End
ENSE00000827431	29767618	29767695
ENSE00001376114	29777155	29777263
ENSE00001391075	29772112	29772198
ENSE00001485939	29764371	29767307
ENSE00001485973	29849512	29850617

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4502 / max 392.7530, expressed in 1767 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136616	9.2094	1597
136618	7.7056	1646
136617	3.7281	1238
136611	2.8547	1002
136619	0.5052	248
136614	0.4516	244
136610	0.3270	135
136609	0.1966	100
136613	0.1686	75
136615	0.1316	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior olivary complex	UBERON:0002127	98.99	gold quality
amniotic fluid	UBERON:0000173	98.77	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.45	gold quality
subthalamic nucleus	UBERON:0001906	98.35	gold quality
substantia nigra pars compacta	UBERON:0001965	98.33	gold quality
medulla oblongata	UBERON:0001896	98.32	gold quality
lateral globus pallidus	UBERON:0002476	98.30	gold quality
superior vestibular nucleus	UBERON:0007227	98.19	gold quality
postcentral gyrus	UBERON:0002581	98.18	gold quality
CA1 field of hippocampus	UBERON:0003881	98.08	gold quality
inferior vagus X ganglion	UBERON:0005363	98.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.91	gold quality
bronchial epithelial cell	CL:0002328	97.90	gold quality
pons	UBERON:0000988	97.89	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.84	gold quality
middle temporal gyrus	UBERON:0002771	97.84	gold quality
parietal lobe	UBERON:0001872	97.80	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.71	gold quality
entorhinal cortex	UBERON:0002728	97.57	gold quality
oral cavity	UBERON:0000167	97.48	gold quality
upper leg skin	UBERON:0004262	97.42	gold quality
orbitofrontal cortex	UBERON:0004167	97.34	gold quality
ventral tegmental area	UBERON:0002691	97.24	gold quality
esophagus squamous epithelium	UBERON:0006920	97.20	gold quality
globus pallidus	UBERON:0001875	97.12	gold quality
superior frontal gyrus	UBERON:0002661	96.93	gold quality
medial globus pallidus	UBERON:0002477	96.83	gold quality
cardia of stomach	UBERON:0001162	96.78	gold quality
biceps brachii	UBERON:0001507	96.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

235 targeting UBL3, 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-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 5)

• posttranslational modification factor that regulates protein sorting to small extracellular vesicles (PMID:30258067)
• We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function (PMID:30323354)
• Identification of a potential tumor suppressor gene, UBL3, in non-small cell lung cancer. (PMID:32296577)
• Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles. (PMID:35197392)
• PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia. (PMID:36672247)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubl3a	ENSDARG00000099532
mus_musculus	Ubl3	ENSMUSG00000001687
rattus_norvegicus	Ubl3	ENSRNOG00000000921
caenorhabditis_elegans		WBGENE00008121

Protein

Protein identifiers

Ubiquitin-like protein 3 — O95164 (reviewed: O95164)

Alternative names: Membrane-anchored ubiquitin-fold protein, Protein HCG-1

All UniProt accessions (1): O95164

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous.

RefSeq proteins (1): NP_009037* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR017000	MUB	Family
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039540	UBL3-like_ubiquitin_dom	Domain
IPR040015	UBL3-like	Family
IPR047977	UBL3_Ubl_met	Domain

Pfam: PF13881

UniProt features (16 total): strand 5, helix 3, lipid moiety-binding region 2, sequence conflict 2, chain 1, propeptide 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2GOW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95164-F1	78.61	0.31

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 (3): 114, 113, 114

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 312 (showing top): GCM_MAP4K4, RORA1_01, LFA1_Q6, TGACCTY_ERR1_Q2, ATGCAGT_MIR217, AP2_Q3, FOXO1_01, GOLDRATH_ANTIGEN_RESPONSE, MODULE_66, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, YY1_02, BRN2_01, BROWNE_HCMV_INFECTION_14HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBL3	UBL5	Q9BZL1	929
UBL3	NEDD8	Q15843	800
UBL3	SUMO1	P55856	798
UBL3	UBL4A	P11441	534
UBL3	LRRC25	Q8N386	480
UBL3	EPS15	P42566	461
UBL3	NOL7	Q9UMY1	447
UBL3	ISG15	P05161	418
UBL3	TP53	P04637	413
UBL3	CLPX	O76031	413
UBL3	HSP90AB1	P08238	393
UBL3	HSP90AA1	P07900	392
UBL3	RAD18	Q9NS91	390
UBL3	CLPP	Q16740	380
UBL3	UFM1	P61960	372

IntAct

31 interactions, top by confidence:

A	B	Type	Score
HDAC7	UBL3	psi-mi:“MI:0915”(physical association)	0.560
	UBL3	psi-mi:“MI:0915”(physical association)	0.560
UBL3	HDAC7	psi-mi:“MI:0915”(physical association)	0.560
UBL3	RBFOX1	psi-mi:“MI:0915”(physical association)	0.560
UBL3	GORASP2	psi-mi:“MI:0915”(physical association)	0.560
UBL3	M1AP	psi-mi:“MI:0915”(physical association)	0.560
UBL3	HEXB	psi-mi:“MI:0915”(physical association)	0.560
UBL3	TTR	psi-mi:“MI:0915”(physical association)	0.560
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
UBL3	RCCD1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
EDAR	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
PDE6D	SUN1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
PDE6D	UBL3	psi-mi:“MI:0914”(association)	0.350
SLC37A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
UBL3		psi-mi:“MI:0915”(physical association)	0.000
UBL3	GORASP2	psi-mi:“MI:0915”(physical association)	0.000
UBL3	RBFOX1	psi-mi:“MI:0915”(physical association)	0.000
UBL3	M1AP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): UBL3 (Affinity Capture-MS), UBL3 (Two-hybrid), UBL3 (Two-hybrid), UBL3 (Two-hybrid), UBL3 (Two-hybrid), M1AP (Two-hybrid), UBL3 (Affinity Capture-MS), UBL3 (Affinity Capture-MS), UBL3 (Affinity Capture-MS), PCP4 (Affinity Capture-MS), UBL3 (Affinity Capture-MS), UBL3 (Affinity Capture-MS), TAX1BP3 (Affinity Capture-MS), TCEAL1 (Affinity Capture-MS), RCCD1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMG1, A2VE52, D3K5L7, E0CZ16, E1C6Q1, E2R222, F1LZ52, F1LZF0, F1MBP6, O13016, O35345, O43791, O60684, O95164, O95198, O95544, P35815, P36993, P54797, P58058, P63143, P63144, Q0IHH9, Q0V7M0, Q0VCW1, Q15645, Q28528, Q28F89, Q2M2N2, Q2TA46, Q3UA06, Q4PJK1, Q5BL35, Q5NVK7, Q5RBV0, Q5REP9, Q5U1X1, Q5XHZ9, Q6GR09, Q6IQ16

Diamond homologs: O95164, Q2TA46, Q5BJT2, Q6Z8K4, Q9Z2M6, Q67UI2, Q75GT2, Q7XRU4, Q8GWJ6, Q8LCS8, Q9LSD8, Q9MAB9, Q9SH14, Q9SW27

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

982 predictions. Top by Δscore:

Variant	Effect	Δscore
13:29767691:TAATG:T	acceptor_gain	1.0000
13:29767694:TG:T	acceptor_gain	1.0000
13:29767696:C:CC	acceptor_gain	1.0000
13:29767698:A:C	acceptor_gain	1.0000
13:29767700:G:C	acceptor_gain	1.0000
13:29767700:G:GC	acceptor_gain	1.0000
13:29772113:T:TA	donor_gain	1.0000
13:29777150:CTCA:C	donor_loss	1.0000
13:29777151:TCACC:T	donor_loss	1.0000
13:29777152:CACCC:C	donor_loss	1.0000
13:29777153:A:AC	donor_gain	1.0000
13:29777153:AC:A	donor_gain	1.0000
13:29777154:C:CC	donor_gain	1.0000
13:29777154:C:T	donor_loss	1.0000
13:29777154:CC:C	donor_gain	1.0000
13:29777259:TTTAT:T	acceptor_gain	1.0000
13:29777260:TTAT:T	acceptor_gain	1.0000
13:29777261:TAT:T	acceptor_gain	1.0000
13:29777263:TCT:T	acceptor_loss	1.0000
13:29777264:C:CC	acceptor_gain	1.0000
13:29777264:CTG:C	acceptor_loss	1.0000
13:29777265:T:C	acceptor_loss	1.0000
13:29820031:A:C	donor_gain	1.0000
13:29820035:ATT:A	donor_gain	1.0000
13:29767692:AATG:A	acceptor_gain	0.9900
13:29767693:ATG:A	acceptor_gain	0.9900
13:29767694:TGC:T	acceptor_loss	0.9900
13:29767695:GC:G	acceptor_loss	0.9900
13:29767697:T:C	acceptor_loss	0.9900
13:29767698:A:AC	acceptor_gain	0.9900

AlphaMissense

770 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:29767646:T:A	R91S	1.000
13:29767646:T:G	R91S	1.000
13:29767647:C:A	R91I	1.000
13:29767647:C:G	R91T	1.000
13:29767656:A:C	L88W	1.000
13:29767656:A:G	L88S	1.000
13:29767658:A:C	H87Q	1.000
13:29767658:A:T	H87Q	1.000
13:29767659:T:C	H87R	1.000
13:29767660:G:C	H87D	1.000
13:29767660:G:T	H87N	1.000
13:29767662:A:C	M86R	1.000
13:29767662:A:T	M86K	1.000
13:29772117:A:G	L73S	1.000
13:29772135:A:G	L67P	1.000
13:29772135:A:T	L67Q	1.000
13:29772137:A:C	F66L	1.000
13:29772137:A:T	F66L	1.000
13:29772138:A:C	F66C	1.000
13:29772138:A:G	F66S	1.000
13:29772139:A:C	F66V	1.000
13:29772139:A:G	F66L	1.000
13:29772141:C:G	R65P	1.000
13:29772144:C:A	G64V	1.000
13:29772144:C:G	G64A	1.000
13:29772144:C:T	G64E	1.000
13:29772145:C:G	G64R	1.000
13:29772145:C:T	G64R	1.000
13:29772147:T:G	Q63P	1.000
13:29772153:A:C	I61S	1.000

dbSNP variants (sampled 300 via entrez): RS1000017030 (13:29849358 G>C), RS1000059176 (13:29807895 T>C), RS1000061417 (13:29786776 G>A), RS1000078232 (13:29816412 G>A), RS1000121705 (13:29764030 T>G), RS1000129117 (13:29806223 A>G,T), RS1000130179 (13:29832161 G>A), RS1000164200 (13:29812897 T>C), RS1000170721 (13:29824861 T>C), RS1000183015 (13:29817120 C>A,T), RS1000209652 (13:29813115 T>C), RS1000220138 (13:29782739 T>C), RS1000233725 (13:29780247 G>A,C), RS1000320134 (13:29806149 C>T), RS1000323042 (13:29789352 T>A,C)

Disease associations

OMIM: gene MIM:604711 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000681_3	Biliary atresia	2.000000e-06
GCST002059_1	Non-word repetition	8.000000e-06
GCST003983_32	Male-pattern baldness	2.000000e-09
GCST004267_6	Blood osmolality (transformed sodium)	5.000000e-06
GCST008163_89	Height	6.000000e-06
GCST008760_7	Perceived sweetness of sucrose	5.000000e-06
GCST009835_2	Left ventricular mass x antihypertensive treatment interaction	5.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005299	non-word reading
EFO:0005405	response to antihypertensive drug
EFO:0009289	left ventricular mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Cadmium Chloride	increases abundance, increases expression	2
dicrotophos	decreases expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
nickel sulfate	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cytarabine	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Etoposide	affects response to substance	1
Lead	affects expression	1
Mitoxantrone	affects response to substance	1
Quercetin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TW02	HAP1 UBL3 (-) 1	Cancer cell line	Male
CVCL_TW03	HAP1 UBL3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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