USP48

Summary

USP48 (ubiquitin specific peptidase 48, HGNC:18533) is a protein-coding gene on chromosome 1p36.12, encoding Ubiquitin carboxyl-terminal hydrolase 48 (Q86UV5). Deubiquitinase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin.

This gene encodes a protein containing domains that associate it with the peptidase family C19, also known as family 2 of ubiquitin carboxyl-terminal hydrolases. Family members function as deubiquitinating enzymes, recognizing and hydrolyzing the peptide bond at the C-terminal glycine of ubiquitin. Enzymes in peptidase family C19 are involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 84196 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal dominant 85 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 348 total — 2 pathogenic
• Phenotypes (HPO): 73
• MANE Select transcript: NM_032236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18533
Approved symbol	USP48
Name	ubiquitin specific peptidase 48
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23277, FLJ11328, FLJ20103, FLJ23054, MGC14879
Ensembl gene	ENSG00000090686
Ensembl biotype	protein_coding
OMIM	617445
Entrez	84196

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 28 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000308271, ENST00000374730, ENST00000374732, ENST00000400301, ENST00000421625, ENST00000464577, ENST00000471752, ENST00000479177, ENST00000487880, ENST00000489108, ENST00000526044, ENST00000527823, ENST00000529637, ENST00000532737, ENST00000534705, ENST00000903043, ENST00000903044, ENST00000903045, ENST00000903046, ENST00000903047, ENST00000903048, ENST00000903049, ENST00000903050, ENST00000903051, ENST00000922669, ENST00000922670, ENST00000922671, ENST00000963813, ENST00000963814, ENST00000963815, ENST00000963816, ENST00000963817, ENST00000963818, ENST00000963819

RefSeq mRNA: 7 — MANE Select: NM_032236 NM_001032730, NM_001330394, NM_001350164, NM_001350166, NM_001350167, NM_001350168, NM_032236

CCDS: CCDS30623, CCDS44084, CCDS81277

Canonical transcript exons

ENST00000308271 — 27 exons

Exon	Start	End
ENSE00000956267	21752527	21752651
ENSE00000956269	21748138	21748271
ENSE00001066209	21706467	21706589
ENSE00001066217	21703512	21703618
ENSE00001132916	21752992	21753119
ENSE00001133036	21728570	21728719
ENSE00001133052	21736446	21736625
ENSE00001177843	21705727	21705837
ENSE00001177848	21706126	21706187
ENSE00001178092	21715389	21715457
ENSE00001178139	21704262	21704392
ENSE00001178188	21706744	21706868
ENSE00001178217	21687191	21687239
ENSE00001276944	21751507	21751615
ENSE00001360466	21678298	21679439
ENSE00001370663	21680808	21680834
ENSE00001746178	21747067	21747149
ENSE00003477833	21721036	21721166
ENSE00003531260	21695066	21695221
ENSE00003558061	21757663	21757783
ENSE00003570833	21756546	21756702
ENSE00003586591	21729704	21729832
ENSE00003606017	21689974	21690099
ENSE00003639615	21701498	21701602
ENSE00003685736	21721650	21721764
ENSE00003784384	21723898	21724095
ENSE00003890465	21782824	21783149

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8962 / max 517.9376, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10876	13.2210	1773
10874	8.4605	1619
10877	2.4098	1269
10875	1.6386	901
10873	0.7265	371
10872	0.3808	222
10871	0.0590	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.30	gold quality
cerebellar hemisphere	UBERON:0002245	97.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.98	gold quality
endothelial cell	CL:0000115	96.86	gold quality
cerebellar cortex	UBERON:0002129	96.83	gold quality
right adrenal gland cortex	UBERON:0035827	96.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.46	gold quality
cerebellum	UBERON:0002037	96.37	gold quality
choroid plexus epithelium	UBERON:0003911	96.23	gold quality
right adrenal gland	UBERON:0001233	96.20	gold quality
tendon	UBERON:0000043	96.08	gold quality
left adrenal gland cortex	UBERON:0035825	96.08	gold quality
adrenal cortex	UBERON:0001235	96.03	gold quality
left adrenal gland	UBERON:0001234	95.88	gold quality
cranial nerve II	UBERON:0000941	95.78	gold quality
adrenal gland	UBERON:0002369	95.62	gold quality
sural nerve	UBERON:0015488	95.51	gold quality
corpus callosum	UBERON:0002336	95.39	gold quality
inferior olivary complex	UBERON:0002127	95.23	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.19	gold quality
tonsil	UBERON:0002372	94.69	gold quality
right ovary	UBERON:0002118	94.53	gold quality
tendon of biceps brachii	UBERON:0008188	94.53	gold quality
colonic epithelium	UBERON:0000397	94.46	gold quality
left ovary	UBERON:0002119	94.42	gold quality
monocyte	CL:0000576	94.34	gold quality
primary visual cortex	UBERON:0002436	94.32	gold quality
ventricular zone	UBERON:0003053	94.28	gold quality
mucosa of stomach	UBERON:0001199	94.26	gold quality
mononuclear cell	CL:0000842	94.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.87
E-CURD-88	no	3.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting USP48, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3202	99.66	67.70	2737

Literature-anchored findings (GeneRIF, showing 21)

• Northern blot analysis revealed a single USP31 transcript of approximately 4 kb, which was primarily expressed in the testis and lung. (PMID:15354349)
• The Overexpression of USP31 in HEK 293T cells inhibited TNFalpha, CD40, LMP1, TRAF2, TRAF6 and IKKbeta-mediated NF-kappaB activation, but did not inhibit Smad-mediated transcription activation. (PMID:16214042)
• data demonstrate a crucial role for the dynamic interaction between D3R and USP48 in the regulation of NHE3 expression and function (PMID:24308971)
• this study demonstrates that USP48 controls the Ubiquitin/proteasome-system-dependent turnover of activated NF-kappaB/RelA in the nucleus. (PMID:25486460)
• In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels. (PMID:28233861)
• study reveals that the USP48-Gli1 regulatory axis is critical for glioma cell proliferation and glioblastoma tumorigenesis. (PMID:28623188)
• down-regulation of USP48 increases E-cadherin expression and epithelial barrier integrity through reducing TRAF2 stability (PMID:28874458)
• Data suggest that ubiquitin specific protease-48 (USP48) promotes genome stability by antagonizing BRCA1 E3 ligase function. (PMID:29335415)
• USP48 inactivation reduces chromosomal instability of Fanconi anemia (FA)-defective cells. Our results highlight a role for USP48 in controlling DNA repair and suggest it as a potential target that could be therapeutically exploited for FA. (PMID:29891926)
• USP48 and BRAF mutations have a role in Cushing’s disease (PMID:30093687)
• the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA. (PMID:30628021)
• USP48 pathogenic variants are relatively frequent in USP8 wild-type Cushing’s disease tumors (PMID:31222332)
• LINC00467 enhances head and neck squamous cell carcinoma progression and the epithelial-mesenchymal transition process via miR-299-5p/ubiquitin specific protease-48 axis. (PMID:32159247)
• USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer. (PMID:32359336)
• USP48 Is Upregulated by Mettl14 to Attenuate Hepatocellular Carcinoma via Regulating SIRT6 Stabilization. (PMID:33903120)
• USP48 Governs Cell Cycle Progression by Regulating the Protein Level of Aurora B. (PMID:34445214)
• USP8, USP48, and BRAF mutations differ in their genotype-phenotype correlation in Asian Indian patients with Cushing’s disease. (PMID:34664215)
• miR-489-3p promotes malignant progression of non-small cell lung cancer through the inactivation of Wnt/beta-catenin signaling pathway via regulating USP48. (PMID:35413838)
• USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection. (PMID:35913642)
• CircUSP48 promotes malignant behavior by regulating CYR61 via miR-365 in osteosarcoma. (PMID:37553503)
• USP48 deubiquitination stabilizes SLC1A5 to inhibit retinal pigment epithelium cell inflammation, oxidative stress and ferroptosis in the progression of diabetic retinopathy. (PMID:38427128)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp48	ENSDARG00000090301
mus_musculus	Usp48	ENSMUSG00000043411
rattus_norvegicus	Usp48	ENSRNOG00000013602

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242), USP32 (ENSG00000170832)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 48 — Q86UV5 (reviewed: Q86UV5)

Alternative names: Deubiquitinating enzyme 48, Ubiquitin thioesterase 48, Ubiquitin-specific peptidase 48, Ubiquitin-specific protease 48, Ubiquitin-specific-processing protease 48

All UniProt accessions (7): Q86UV5, A0A0A0MRS6, E9PJ87, E9PJ93, E9PJH5, E9PRY5, H3BLX5

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of polyubiquitin precursors as well as that of ubiquitinated proteins. Plays a role in the regulation of NF-kappa-B activation by TNF receptor superfamily via its interactions with RELA and TRAF2. May also play a regulatory role at postsynaptic sites. Plays an important role in cell cycle progression by deubiquitinating Aurora B/AURKB and thereby extending its stability. In the context of H.pylori infection, stabilizes nuclear RELA through deubiquitination, thereby promoting the transcriptional activity of RELA to prolong TNFAIP3 de novo synthesis. Consequently, TNFAIP3 suppresses caspase activity and apoptotic cell death. Also functions in the modulation of the ciliary and synaptic transport as well as cytoskeleton organization, which are key for photoreceptor function and homeostasis. To achieve this, stabilizes the levels of the retinal degeneration-associated proteins ARL3 and UNC119 using distinct mechanisms. Plays a positive role in pyroptosis by stabilizing gasdermin E/GSDME through removal of its ‘Lys-48’-linked ubiquitination.

Subunit / interactions. Interacts with TRAF2 and RELA. Interacts with GPS1.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Cilium.

Tissue specificity. Widely expressed. Expressed in the fetal inner ear.

Disease relevance. Deafness, autosomal dominant, 85 (DFNA85) [MIM:620227] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA85 is characterized by progressive hearing loss, with onset in childhood or young adulthood. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase C19 family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q86UV5-1	1	yes
Q86UV5-2	2
Q86UV5-3	3
Q86UV5-4	4
Q86UV5-5	5
Q86UV5-6	6
Q86UV5-7	7, USP31S1
Q86UV5-8	8

RefSeq proteins (7): NP_001027902, NP_001317323, NP_001337093, NP_001337095, NP_001337096, NP_001337097, NP_115612* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR001394	Peptidase_C19_UCH	Domain
IPR006615	Pept_C19_DUSP	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033841	Pep_USP48	Domain
IPR035927	DUSP-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR044743	Ubl_USP48	Domain
IPR050164	Peptidase_C19	Family

Pfam: PF00443, PF06337

UniProt features (36 total): splice variant 13, domain 5, modified residue 4, sequence variant 4, compositionally biased region 3, active site 2, mutagenesis site 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UV5-F1	81.44	0.51

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): 98 (nucleophile); 353 (proton acceptor)

Post-translational modifications (4): 886, 887, 888, 956

Mutagenesis-validated functional residues (2):

Position	Phenotype
98	loss of deubiquitinase activity.
1019–1035	loss of deubiquitinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 514 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOLDRATH_IMMUNE_MEMORY, TGACCTY_ERR1_Q2, GGAMTNNNNNTCCY_UNKNOWN, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GGGCATT_MIR365, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, ATF1_Q6, BLALOCK_ALZHEIMERS_DISEASE_UP, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, USF_01, E4F1_Q6, LIAO_METASTASIS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

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

GO Molecular Function (7): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), deubiquitinase activity (GO:0101005), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), cilium (GO:0005929), cytoplasm (GO:0005737), cell projection (GO:0042995)

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
intracellular membrane-bounded organelle	2
cytoplasm	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
ubiquitin-like protein peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear lumen	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1419 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP48	USP5	P45974	601
USP48	ZUP1	Q96AP4	575
USP48	USP13	Q92995	574
USP48	USP39	Q53GS9	567
USP48	USP30	Q70CQ3	560
USP48	VCPIP1	Q96JH7	560
USP48	PSMD14	O00487	544
USP48	USP53	Q70EK8	498
USP48	JOSD1	Q15040	488
USP48	USP26	Q9BXU7	487
USP48	OTUB1	Q96FW1	486
USP48	UCHL3	P15374	484
USP48	USP37	Q86T82	483
USP48	USP32	Q8NFA0	482
USP48	OTUD6B	Q8N6M0	456
USP48	PAN2	Q504Q3	456

IntAct

30 interactions, top by confidence:

A	B	Type	Score
TARDBP	USP48	psi-mi:“MI:0915”(physical association)	0.560
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
	USP48	psi-mi:“MI:0915”(physical association)	0.400
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
USP21	ANKRD28	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
FMNL2	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCL16	USP9Y	psi-mi:“MI:0914”(association)	0.350
ZNF232	ZNF197	psi-mi:“MI:0914”(association)	0.350
H2BC11	FGA	psi-mi:“MI:0914”(association)	0.350
USP48	UBB	psi-mi:“MI:0914”(association)	0.350
NR1D2	NR1D1	psi-mi:“MI:0914”(association)	0.350
FCHO1	EPS15	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SNW1		psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
RBM15	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
UTP3	NACA	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
CEP63	USP48	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (255): SLC9A3 (Affinity Capture-Western), USP48 (Affinity Capture-MS), USP48 (Affinity Capture-Western), USP48 (Biochemical Activity), DYNC1LI1 (Co-fractionation), NCBP2 (Co-fractionation), NUP188 (Co-fractionation), USP48 (Co-fractionation), USP48 (Affinity Capture-MS), USP48 (Proximity Label-MS), USP48 (Proximity Label-MS), USP48 (Affinity Capture-MS), NDUFAF7 (Affinity Capture-MS), USP48 (Affinity Capture-MS), RNF123 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IB93, A1A5P5, A1Z7K9, A2XDG4, A3AF13, A3KMI0, A6QR55, B2GUZ1, D3ZJ96, F6V6I0, F6Z5C0, F8VPZ3, O22207, P29375, P35123, P51784, Q09879, Q13107, Q14149, Q2HJE4, Q30DN6, Q3UXZ9, Q3V0C5, Q5D006, Q5I043, Q5RCD3, Q5ZID5, Q5ZM45, Q62240, Q6NZP1, Q76LT8, Q80U87, Q80Y84, Q86UV5, Q8BWR4, Q8NFA0, Q8R5C8, Q8R5H1, Q93Y01, Q96RU2

Diamond homologs: A0A0R4IB93, A0JM59, A1CIL1, A1CW53, A2XDG4, A3AF13, A5PN09, A6QNM7, A7Z056, B1WBD7, B2GUZ1, B8NSV5, D3ZJ96, F6Z5C0, O22207, O60079, O94966, Q0CT11, Q0E2F9, Q0VA64, Q13107, Q2HJE4, Q2UUG8, Q3UJD6, Q3V0C5, Q4VSI4, Q5I043, Q5R5Z6, Q5RCD3, Q5ZM45, Q60MK8, Q6A4J8, Q6J1Y9, Q6PAW2, Q6U7I1, Q6ZQ93, Q70CQ2, Q76LT8, Q7JKC3, Q84WU2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
Amyloid fiber formation	5	24.5×	6e-04
Ub-specific processing proteases	5	12.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	263
Likely benign	16
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2443812	NM_032236.8(USP48):c.1216G>A (p.Gly406Arg)	Pathogenic
2443813	NM_032236.8(USP48):c.2215_2216delinsTT (p.Thr739Leu)	Pathogenic

SpliceAI

7900 predictions. Top by Δscore:

Variant	Effect	Δscore
16:23072058:C:CA	donor_gain	1.0000
16:23072193:GGAGC:G	acceptor_gain	1.0000
16:23072197:CCTG:C	acceptor_loss	1.0000
16:23072198:C:CC	acceptor_gain	1.0000
16:23073719:CAC:C	donor_loss	1.0000
16:23073720:A:AG	donor_loss	1.0000
16:23073721:CCT:C	donor_loss	1.0000
16:23073723:TGCC:T	donor_gain	1.0000
16:23073876:GTACG:G	acceptor_gain	1.0000
16:23073877:TACG:T	acceptor_gain	1.0000
16:23073879:CG:C	acceptor_gain	1.0000
16:23073881:C:CC	acceptor_gain	1.0000
16:23082554:CAAG:C	acceptor_gain	1.0000
16:23082558:C:CC	acceptor_gain	1.0000
16:23084854:TCTTA:T	donor_loss	1.0000
16:23084855:CTTAC:C	donor_loss	1.0000
16:23084856:TTA:T	donor_loss	1.0000
16:23084857:TACCC:T	donor_loss	1.0000
16:23084858:A:AC	donor_gain	1.0000
16:23084858:A:C	donor_loss	1.0000
16:23084858:AC:A	donor_gain	1.0000
16:23084859:C:CC	donor_gain	1.0000
16:23084859:CC:C	donor_gain	1.0000
16:23084859:CCCG:C	donor_gain	1.0000
16:23084985:ATAAG:A	acceptor_gain	1.0000
16:23084986:TAAG:T	acceptor_gain	1.0000
16:23084987:AAG:A	acceptor_gain	1.0000
16:23084988:AG:A	acceptor_gain	1.0000
16:23084988:AGC:A	acceptor_loss	1.0000
16:23084989:GC:G	acceptor_loss	1.0000

AlphaMissense

6878 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:21680808:C:G	G1029R	1.000
1:21680812:A:C	F1027L	1.000
1:21680812:A:T	F1027L	1.000
1:21680813:A:C	F1027C	1.000
1:21680813:A:G	F1027S	1.000
1:21680814:A:G	F1027L	1.000
1:21689978:A:C	L1002W	1.000
1:21689978:A:G	L1002S	1.000
1:21690059:A:G	L975S	1.000
1:21690064:C:A	Q973H	1.000
1:21690064:C:G	Q973H	1.000
1:21690065:T:G	Q973P	1.000
1:21690077:G:T	A969D	1.000
1:21690080:A:T	V968D	1.000
1:21695103:A:T	V949D	1.000
1:21703537:A:T	V866D	1.000
1:21703603:C:G	C844S	1.000
1:21703604:A:G	C844R	1.000
1:21703604:A:T	C844S	1.000
1:21703613:A:G	C841R	1.000
1:21705785:A:G	C776R	1.000
1:21706142:A:G	W753R	1.000
1:21706142:A:T	W753R	1.000
1:21715398:A:G	C652R	1.000
1:21721126:A:G	W602R	1.000
1:21721126:A:T	W602R	1.000
1:21724057:A:G	W497R	1.000
1:21724057:A:T	W497R	1.000
1:21724069:A:G	W493R	1.000
1:21724069:A:T	W493R	1.000

dbSNP variants (sampled 300 via entrez): RS1000060288 (1:21686114 A>C,T), RS1000107019 (1:21709042 C>T), RS1000134886 (1:21759660 T>C,G), RS1000152195 (1:21722455 C>T), RS1000163374 (1:21732360 G>A), RS1000166869 (1:21771804 A>C), RS1000179043 (1:21719458 G>T), RS1000265767 (1:21722746 G>C), RS1000310822 (1:21682692 T>C), RS1000359350 (1:21775072 A>G), RS1000366485 (1:21771519 A>C), RS1000384961 (1:21682547 T>C), RS1000400714 (1:21716734 C>T), RS1000493570 (1:21688431 C>G,T), RS1000537885 (1:21701219 A>G)

Disease associations

OMIM: gene MIM:617445 | disease phenotypes: MIM:620227

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal dominant 85	Strong	Autosomal dominant
schizophrenia	No Known Disease Relationship	Unknown

Mondo (4): prostate cancer (MONDO:0008315), hearing loss, autosomal dominant 85 (MONDO:0859366), sensorineural hearing loss disorder (MONDO:0020678), schizophrenia (MONDO:0005090)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000141	Amenorrhea
HP:0000407	Sensorineural hearing impairment
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000725	Psychotic episodes
HP:0000726	Dementia
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000869	Secondary amenorrhea
HP:0000876	Oligomenorrhea
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0000963	Thin skin
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0001007	Hirsutism
HP:0001050	Plethora
HP:0001058	Poor wound healing
HP:0001061	Acne
HP:0001065	Striae distensae
HP:0001123	Visual field defect
HP:0001297	Stroke
HP:0001324	Muscle weakness
HP:0001626	Abnormality of the cardiovascular system
HP:0001658	Myocardial infarction
HP:0001888	Decreased total lymphocyte count
HP:0001956	Truncal obesity

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST003784_15	Multiple system atrophy	5.000000e-06
GCST004611_103	High light scatter reticulocyte count	7.000000e-28
GCST004612_193	High light scatter reticulocyte percentage of red cells	2.000000e-28
GCST004628_3	Immature fraction of reticulocytes	8.000000e-62
GCST006288_339	Heel bone mineral density	1.000000e-08
GCST006288_445	Heel bone mineral density	4.000000e-10
GCST007576_209	Chronotype	5.000000e-09
GCST007847_92	Type 2 diabetes	2.000000e-09
GCST90002385_601	High light scatter reticulocyte count	6.000000e-39
GCST90002386_305	High light scatter reticulocyte percentage of red cells	4.000000e-20
GCST90002386_306	High light scatter reticulocyte percentage of red cells	6.000000e-40
GCST90002387_189	Immature fraction of reticulocytes	5.000000e-43
GCST90002387_190	Immature fraction of reticulocytes	5.000000e-81
GCST90002405_591	Reticulocyte count	8.000000e-21
GCST90002406_129	Reticulocyte fraction of red cells	5.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
Acetaminophen	increases expression, decreases expression	2
Rotenone	increases expression, decreases expression	2
Copper Sulfate	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases response to substance	1
Atrazine	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ivermectin	decreases expression	1
Methamphetamine	affects response to substance	1
Oligomycins	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	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_TX04	HAP1 USP48 (-) 1	Cancer cell line	Male
CVCL_TX05	HAP1 USP48 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety