USP12

Summary

USP12 (ubiquitin specific peptidase 12, HGNC:20485) is a protein-coding gene on chromosome 13q12.13, encoding Ubiquitin carboxyl-terminal hydrolase 12 (O75317). Deubiquitinating enzyme that plays various roles in the regulation of the immune response and inflammation.

Enables cysteine-type deubiquitinase activity and cysteine-type endopeptidase activity. Involved in protein deubiquitination. Located in cytoplasm; nucleus; and plasma membrane.

Source: NCBI Gene 219333 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 38 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_182488

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20485
Approved symbol	USP12
Name	ubiquitin specific peptidase 12
Location	13q12.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152484
Ensembl biotype	protein_coding
OMIM	603091
Entrez	219333

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000282344, ENST00000612674, ENST00000620323, ENST00000915651, ENST00000963737

RefSeq mRNA: 1 — MANE Select: NM_182488 NM_182488

CCDS: CCDS31952

Canonical transcript exons

ENST00000282344 — 9 exons

Exon	Start	End
ENSE00001005457	27090082	27090158
ENSE00001005458	27071071	27071149
ENSE00001005460	27089883	27089966
ENSE00001005463	27075191	27075388
ENSE00001005466	27095601	27095830
ENSE00001005467	27105731	27105944
ENSE00001005468	27116516	27116596
ENSE00001373218	27066156	27069384
ENSE00001488438	27171592	27171811

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 93.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.3233 / max 67.8986, expressed in 924 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136484	30.5276	1801
136483	2.3233	924

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	93.57	gold quality
saphenous vein	UBERON:0007318	93.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.04	gold quality
islet of Langerhans	UBERON:0000006	92.71	gold quality
cartilage tissue	UBERON:0002418	92.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.66	gold quality
calcaneal tendon	UBERON:0003701	92.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.18	gold quality
lower esophagus	UBERON:0013473	92.14	gold quality
epithelium of nasopharynx	UBERON:0001951	91.79	gold quality
dorsal root ganglion	UBERON:0000044	91.74	gold quality
bone marrow	UBERON:0002371	91.64	gold quality
corpus callosum	UBERON:0002336	91.60	gold quality
trabecular bone tissue	UBERON:0002483	91.55	gold quality
frontal pole	UBERON:0002795	91.40	gold quality
right lung	UBERON:0002167	91.35	gold quality
bone element	UBERON:0001474	91.34	gold quality
rectum	UBERON:0001052	91.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.32	gold quality
colonic epithelium	UBERON:0000397	91.31	gold quality
germinal epithelium of ovary	UBERON:0001304	91.25	gold quality
sigmoid colon	UBERON:0001159	91.20	gold quality
monocyte	CL:0000576	91.09	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.06	gold quality
paraflocculus	UBERON:0005351	91.02	gold quality
mononuclear cell	CL:0000842	90.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.96	gold quality
visceral pleura	UBERON:0002401	90.63	gold quality
choroid plexus epithelium	UBERON:0003911	90.61	gold quality
leukocyte	CL:0000738	90.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

241 targeting USP12, 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-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-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Literature-anchored findings (GeneRIF, showing 20)

• two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 (PMID:19075014)
• WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1 x USP12 complexes (PMID:20147737)
• The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradation. (PMID:22778262)
• Usp12 acts in a pro-proliferative manner by stabilizing AR and enhancing its cellular function. (PMID:24056413)
• our results reveal WDR48 and USP12 as novel PHLPP1 regulators and potential suppressors of tumor cell survival (PMID:24145035)
• Coimmunoprecipitation experiments indicated that human papillomavirus type 31 E1 assembles into a ternary complex with UAF1 and any one of these three USPs: USP1, USP12 and USP46. (PMID:24850727)
• Usp12 directly deubiquitinates and stabilises the Akt phosphatases PHLPP and PHLPPL resulting in decreased levels of active pAkt. (PMID:25216524)
• Results suggest role for USP46/USP12 in Epstein-Barr virus induced growth transformation. (PMID:25855980)
• Usp12 deubiquitylates and prevents lysosomal degradation of LAT and Trat1 to maintain the proximal TCR complex for the duration of signaling. (PMID:26811477)
• UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center, allosterically activating the enzyme. (PMID:27373336)
• Our results highlight the interfaces essential for regulation of USP12 activity and show a conserved second binding of UAF1 which could be important for regulatory functions independent of USP12 activity. (PMID:27650958)
• USP12 deubiquitinates MDM2 and AR, which in turn controls the levels of the TP53 tumour suppressor and AR oncogene in prostate cancer. (PMID:29755129)
• Findings indicate that deubiquitinase Usp12 (Usp12) overexpression accelerates autophagic flux and induces an approximately sixfold increase in autophagic structures as determined by ultrastructural analyses. (PMID:30266909)
• WDR20 plays a crucial role in as a “targeting subunit” that modulates CRM1-dependent shuttling of the USP12/UAF1/WDR20 complex between the plasma membrane, cytoplasm and nucleus. (PMID:30466959)
• Downregulation of USP12 inhibits tumor growth via the p38/MAPK pathway in hepatocellular carcinoma. (PMID:33174033)
• USP12 downregulation orchestrates a protumourigenic microenvironment and enhances lung tumour resistance to PD-1 blockade. (PMID:34381028)
• USP12 positively regulates M-MDSC function to inhibit antitumour immunity through deubiquitinating and stabilizing p65. (PMID:35898171)
• USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2. (PMID:37341611)
• USP12 regulates ER stress-associated osteogenesis in human periodontal ligament cells under tension stress. (PMID:38113977)
• WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc. (PMID:39432777)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp12b	ENSDARG00000074367
danio_rerio	usp12a	ENSDARG00000078109
mus_musculus	Usp12	ENSMUSG00000029640
rattus_norvegicus	Usp12	ENSRNOG00000033411
rattus_norvegicus	Usp12l1	ENSRNOG00000064535
drosophila_melanogaster	Usp12-46	FBGN0039025
caenorhabditis_elegans		WBGENE00011216

Paralogs (2): USP46 (ENSG00000109189), USP39 (ENSG00000168883)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 12 — O75317 (reviewed: O75317)

Alternative names: Deubiquitinating enzyme 12, Ubiquitin specific peptidase 12, Ubiquitin thioesterase 12, Ubiquitin-hydrolyzing enzyme 1, Ubiquitin-specific-processing protease 12

All UniProt accessions (3): O75317, A0A087WUU2, A0A087WWP2

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme that plays various roles in the regulation of the immune response and inflammation. During TCR engagement and activation, translocates into the cytoplasm and deubiquitinates its substrates LAT and TRAT1 and prevents their lysosome-dependent degradation to stabilize the TCR signaling complex at the plasma membrane. Plays an essential role in the selective LPS-induced macrophage response through the activation of NF-kappa-B pathway. In addition, promotes that antiviral immune response through targeting DNA sensor IFI16 to inhibit its proteasome-dependent degradation. Participates in the interferon signaling pathway and antiviral response independently of its deubiquitinase activity by maintaining nuclear phosphorylated STAT1 levels via inhibition of its CREBBP-mediated acetylation and subsequent dephosphorylation. Plays an intrinsic role in promoting the differentiation, activation and proliferation of CD4(+) T-cell by activating the NF-kappa-B signaling pathway through deubiquitinating and stabilizing B-cell lymphoma/leukemia 10/BCL10. In myeloid-derived suppressor cells promotes the activation of the NF-kappa-B via deubiquitination and stabilization of RELA. Regulates the ‘Lys-63’-linked polyubiquitin chains of BAX and thereby modulates the mitochondrial apoptotic process. Negative regulator of NOTCH signaling that specifically deubiquitinates non-activated NOTCH receptors to target them for lysosomal degradation; deubiquitination of NOTCH stimulates its transport form late endosomes to lysosomes. Protects neurons against HTT/huntingtin-induced polyglutamine expansion-dependent neurodegeneration through regulation of autophagic flux. This function is independent of deubiquitinase activity or of other components of the USP12-WDR20-WDR48 deubiquitinating complex. In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability. (Microbial infection) Forms a complex with Epstein-Barr virus protein EBNA3 which is an active deubiquitinase activity that may select specific substrates to promote B-lymphocyte transformation.

Subunit / interactions. Interacts with WDR48. Interacts with WDR20; this interaction promotes translocation of the USP12 complex to the plasma membrane. Component of the USP12-WDR20-WDR48 deubiquitinating complex. Component of the USP12-DMWD-WDR48 deubiquitinating complex. Interacts with PHLPP1. Interacts with RBPJ. Interacts with CBP; this interaction blocks the acetyltransferase activity of CREBBP. Interacts with ITCH; the interaction is more efficient when both USP12 and WDR48/UAF1 are involved and may mediate recruitment of the USP12 deubiquitinating complex to Notch. Interacts with OPTN and SQSTM1/p62; the interaction is independent of deubiquitinase activity and may be involved in regulation of autophagic flux. (Microbial infection) Interacts with Epstein-Barr virus protein EBNA3.

Subcellular location. Nucleus. Cytoplasm. Cell membrane.

Activity regulation. Activated by interaction with WDR20, WDR48 and DMWD through different allosteric mechanisms.

Induction. By LPS in stimulated macrophages.

Miscellaneous. Knockdown of USP12 increases Akt activation.

Similarity. Belongs to the peptidase C19 family. USP12/USP46 subfamily.

RefSeq proteins (1): NP_872294* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443

UniProt features (61 total): strand 21, helix 13, mutagenesis site 10, turn 5, binding site 4, active site 2, chain 1, domain 1, region of interest 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5K1A	X-RAY DIFFRACTION	2.3
5K16	X-RAY DIFFRACTION	2.6
5L8W	X-RAY DIFFRACTION	2.79
5K1C	X-RAY DIFFRACTION	3
5K1B	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75317-F1	89.00	0.72

Functional residue map

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

Catalytic / active sites (2): 48 (nucleophile); 317 (proton acceptor)

Ligand- & substrate-binding residues (4): 236; 186; 189; 233

Mutagenesis-validated functional residues (10):

Position	Phenotype
48	abolishes catalytic activity. retains the ability to protect against htt/huntingtin-induced polyglutamine expansion-depe
48	abolishes catalytic activity. reduced deubiquitination of notch. retains the ability to protect against htt/huntingtin-i
190	impaired binding to wdr48.
208–210	loss of activity.
219	loss of activity.
240	impaired binding to wdr48; when associated with a-241.
241	impaired binding to wdr48; when associated with a-240.
264	strong reduction of activity.
279	impaired binding to wdr20; when associated with a-287. impaired binding to dmwd; when associated with a-287. does not pr
287	impaired binding to wdr20; when associated with a-279. impaired binding to dmwd; when associated with a-279. does not pr

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 237 (showing top): GGGTGGRR_PAX4_03, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, EFC_Q6, LINDSTEDT_DENDRITIC_CELL_MATURATION_B, FOSTER_TOLERANT_MACROPHAGE_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, HNF4_DR1_Q3, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, TGANTCA_AP1_C, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, PPAR_DR1_Q2, GOBP_REGULATION_OF_PROTEIN_STABILITY, AACTTT_UNKNOWN, RFX1_02

GO Biological Process (3): proteolysis (GO:0006508), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647)

GO Molecular Function (8): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), deubiquitinase activity (GO:0101005)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cysteine-type peptidase activity	2
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
endopeptidase activity	1
deubiquitinase activity	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
ubiquitin-like protein peptidase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP12	WDR48	Q8TAF3	990
USP12	ZUP1	Q96AP4	938
USP12	WDR20	Q8TBZ3	934
USP12	PHLPP1	O60346	722
USP12	DMWD	Q09019	662
USP12	PHLPP2	Q6ZVD8	656
USP12	USP13	Q92995	552
USP12	USP7	Q93009	508
USP12	USP28	Q96RU2	507
USP12	JOSD1	Q15040	504
USP12	MYSM1	Q5VVJ2	504
USP12	UCHL3	P15374	489
USP12	YOD1	Q5VVQ6	487
USP12	USP46	P62068	478
USP12	USP25	Q9UHP3	478

IntAct

66 interactions, top by confidence:

A	B	Type	Score
USP12	WDR20	psi-mi:“MI:0915”(physical association)	0.800
WDR20	USP12	psi-mi:“MI:0914”(association)	0.800
PHLPP2	NHERF1	psi-mi:“MI:0914”(association)	0.760
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
WDR20	PHLPP1	psi-mi:“MI:0914”(association)	0.670
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
USP12	PHLPP1	psi-mi:“MI:0914”(association)	0.570
PHLPP1	USP12	psi-mi:“MI:0914”(association)	0.570
CALR	USP12	psi-mi:“MI:0915”(physical association)	0.560
DLST	USP12	psi-mi:“MI:0915”(physical association)	0.560
NEK7	USP12	psi-mi:“MI:0915”(physical association)	0.560
TSPYL6	NME4	psi-mi:“MI:0914”(association)	0.530
VSX2	USP12	psi-mi:“MI:0914”(association)	0.530
GPR161	USP12	psi-mi:“MI:0914”(association)	0.530
HSPB9	USP12	psi-mi:“MI:0914”(association)	0.530
WDR48	USP12	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
RAD51AP1	USP12	psi-mi:“MI:0914”(association)	0.530

BioGRID (148): USP12 (Affinity Capture-Western), USP12 (Affinity Capture-Western), USP12 (Affinity Capture-Western), NOTCH1 (Biochemical Activity), USP12 (Affinity Capture-MS), USP12 (Affinity Capture-Western), USP12 (Affinity Capture-MS), CBLB (Proximity Label-MS), ITCH (Proximity Label-MS), WDR48 (Proximity Label-MS), ZAP70 (Proximity Label-MS), WDR20 (Proximity Label-MS), USP46 (Proximity Label-MS), LAT (Proximity Label-MS), GRB2 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2JTR4, A4FUN7, A5D9H7, A5WWB0, A6H8I0, A6NNY8, A6QNS3, C0HB46, D0RB01, E1C1R4, F1M625, O24454, O75317, P09851, P0C8Z3, P20936, P50904, P62068, P62069, Q09LZ8, Q12979, Q16288, Q3TIX9, Q52KZ6, Q53GS9, Q5DU02, Q5F415, Q5F450, Q5IFJ9, Q5IS37, Q5IS82, Q5M981, Q5R573, Q5R761, Q5R8I6, Q5RBQ4, Q5RDP3, Q5SSL4, Q60969, Q6DCJ1

Diamond homologs: A0A0R4IB93, A1CIL1, A1CW53, A2Q9N1, A4FUN7, A5D9H7, A5PJS6, A5WWB0, A6QR55, B0Y4P5, B2GUZ1, B3LGK1, B8NSV5, C0HB46, D0RB01, E2RK09, E7F6T8, E9Q9U0, F1M625, F1N5V1, G5E8G2, G5E8I7, O22207, O24454, O57429, O60079, O75317, O94966, P34547, P35123, P35125, P38187, P39967, P40818, P50102, P51784, P52479, P62068, P62069, Q01988

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1048617	GRCh37/hg19 13q11-34(chr13:19053605-115108528)x3	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:27069300:A:C	Y366D	1.000
13:27069305:A:G	L364P	1.000
13:27069312:A:G	Y362H	1.000
13:27069350:C:T	G349E	1.000
13:27069351:C:A	G349W	1.000
13:27069351:C:G	G349R	1.000
13:27069351:C:T	G349R	1.000
13:27071083:G:C	D333E	1.000
13:27071083:G:T	D333E	1.000
13:27071084:T:A	D333V	1.000
13:27071084:T:C	D333G	1.000
13:27071084:T:G	D333A	1.000
13:27071085:C:A	D333Y	1.000
13:27071085:C:G	D333H	1.000
13:27071100:A:G	W328R	1.000
13:27071100:A:T	W328R	1.000
13:27071130:A:G	Y318H	1.000
13:27071131:A:C	H317Q	1.000
13:27071131:A:T	H317Q	1.000
13:27071133:G:C	H317D	1.000
13:27071135:C:A	G316V	1.000
13:27071135:C:T	G316D	1.000
13:27071136:C:G	G316R	1.000
13:27075194:C:T	G310E	1.000
13:27075201:G:C	H308D	1.000
13:27075213:C:G	A304P	1.000
13:27075218:A:G	L302P	1.000
13:27075272:A:G	L284P	1.000
13:27075283:A:C	F280L	1.000
13:27075283:A:T	F280L	1.000

dbSNP variants (sampled 300 via entrez): RS1000002765 (13:27099250 T>C), RS1000015659 (13:27131398 A>G), RS1000095417 (13:27099523 A>G), RS1000149130 (13:27167472 A>G,T), RS1000194748 (13:27123472 A>G), RS1000197663 (13:27122569 A>C), RS1000208480 (13:27118165 G>A), RS1000225838 (13:27123105 A>T), RS1000233106 (13:27073720 T>C), RS1000233314 (13:27079723 T>C), RS1000242147 (13:27073533 T>A), RS1000262636 (13:27117239 T>A), RS1000291989 (13:27160148 A>C,T), RS1000302472 (13:27092377 T>C), RS1000311267 (13:27086606 C>T)

Disease associations

OMIM: gene MIM:603091 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000529_3	Ulcerative colitis	7.000000e-08
GCST000977_2	Alcohol dependence	5.000000e-06
GCST003817_11	Mortality in sepsis	1.000000e-06
GCST005025_16	Anti-saccade response	8.000000e-06
GCST006110_19	Nose morphology	5.000000e-06
GCST90011899_153	Aspartate aminotransferase levels	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0006874	antisaccade response measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5291973 (PROTEIN COMPLEX), CHEMBL6067593 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression	4
Estradiol	affects cotreatment, increases expression, affects expression	3
sodium arsenite	affects methylation, increases expression	2
Lead	affects splicing, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Vehicle Emissions	decreases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Bucladesine	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Phenobarbital	affects expression	1
Rotenone	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5251154	Binding	Inhibition of USP12/UAF1/WDR20 (unknown origin) using ubiquitin rhodamine 110 as substrate at 1 to 10 uM by DUBprofiler fluorometric assay	Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KT	N/Tert-1 USP12	Telomerase immortalized cell line	Male
CVCL_TW53	HAP1 USP12 (-) 1	Cancer cell line	Male
CVCL_TW54	HAP1 USP12 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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