USP53

Summary

USP53 (ubiquitin specific peptidase 53, HGNC:29255) is a protein-coding gene on chromosome 4q26, encoding Ubiquitin carboxyl-terminal hydrolase 53 (Q70EK8). Deubiquitinase that mediates ‘Lys-63’-linked deubiquitination of tight junction proteins, such as MARVELD2 and LSR, and which is involved in the survival of auditory hair cells and hearing.

Enables K63-linked deubiquitinase activity. Predicted to be involved in response to auditory stimulus and sensory perception of sound. Predicted to act upstream of or within action potential; epithelial cell apoptotic process; and outer hair cell apoptotic process. Located in bicellular tight junction. Implicated in progressive familial intrahepatic cholestasis.

Source: NCBI Gene 54532 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cholestasis (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 271 total — 19 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 17
• MANE Select transcript: NM_001371395

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29255
Approved symbol	USP53
Name	ubiquitin specific peptidase 53
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1350
Ensembl gene	ENSG00000145390
Ensembl biotype	protein_coding
OMIM	617431
Entrez	54532

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000274030, ENST00000450251, ENST00000507597, ENST00000507906, ENST00000509769, ENST00000510737, ENST00000510852, ENST00000514305, ENST00000514665, ENST00000688980, ENST00000692078, ENST00000883044, ENST00000883045, ENST00000883046, ENST00000883047, ENST00000916005, ENST00000971122, ENST00000971123

RefSeq mRNA: 16 — MANE Select: NM_001371395 NM_001371395, NM_001371396, NM_001371397, NM_001371398, NM_001371399, NM_001389658, NM_001389659, NM_001389660, NM_001389661, NM_001389662, NM_001389663, NM_001389664, NM_001389665, NM_001389666, NM_001389667, NM_019050

CCDS: CCDS43265, CCDS93614

Canonical transcript exons

ENST00000692078 — 19 exons

Exon	Start	End
ENSE00000970335	119256441	119256523
ENSE00000970336	119259820	119259925
ENSE00000970337	119260507	119260653
ENSE00000970338	119261715	119261864
ENSE00001482300	119256246	119256359
ENSE00001482301	119248748	119248882
ENSE00001482303	119245337	119245429
ENSE00001482305	119239218	119239903
ENSE00001482306	119214070	119214222
ENSE00001482307	119212713	119212873
ENSE00001536378	119235290	119235411
ENSE00001536381	119217550	119217673
ENSE00001743932	119292338	119295518
ENSE00003474013	119269691	119269837
ENSE00003526693	119273632	119273708
ENSE00003594106	119267320	119267482
ENSE00003622693	119268268	119268420
ENSE00003641701	119271296	119272034
ENSE00003691023	119291165	119291261

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.0186 / max 565.4007, expressed in 1726 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49481	15.4191	1675
49480	1.9528	1058
49479	1.3499	660
49478	1.0763	510
49484	0.5031	225
49483	0.2652	131
49485	0.2146	90
49486	0.1422	67
49482	0.0953	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.56	gold quality
tibial nerve	UBERON:0001323	98.05	gold quality
mucosa of stomach	UBERON:0001199	97.00	gold quality
right lung	UBERON:0002167	96.57	gold quality
germinal epithelium of ovary	UBERON:0001304	95.81	gold quality
sural nerve	UBERON:0015488	95.29	gold quality
lower lobe of lung	UBERON:0008949	95.24	gold quality
colonic epithelium	UBERON:0000397	95.03	gold quality
trigeminal ganglion	UBERON:0001675	94.97	gold quality
tibia	UBERON:0000979	94.96	gold quality
caput epididymis	UBERON:0004358	94.49	gold quality
corpus epididymis	UBERON:0004359	94.33	gold quality
buccal mucosa cell	CL:0002336	94.26	gold quality
right uterine tube	UBERON:0001302	94.18	gold quality
tendon	UBERON:0000043	94.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.65	gold quality
cauda epididymis	UBERON:0004360	93.48	gold quality
colonic mucosa	UBERON:0000317	92.99	gold quality
biceps brachii	UBERON:0001507	92.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.91	gold quality
pericardium	UBERON:0002407	92.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.63	gold quality
upper lobe of lung	UBERON:0008948	92.24	gold quality
gastrocnemius	UBERON:0001388	92.21	gold quality
upper lobe of left lung	UBERON:0008952	92.20	gold quality
amniotic fluid	UBERON:0000173	92.13	gold quality
thoracic aorta	UBERON:0001515	92.03	gold quality
ascending aorta	UBERON:0001496	91.94	gold quality
muscle of leg	UBERON:0001383	91.71	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2897.98
E-HCAD-10	yes	52.14
E-MTAB-10287	yes	35.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

150 targeting USP53, 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-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
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-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 8)

• Low-GGT intrahepatic cholestasis associated with biallelic USP53 variants: Clinical, histological and ultrastructural characterization. (PMID:32124521)
• Knockdown of Ubiquitin-Specific Protease 53 Enhances the Radiosensitivity of Human Cervical Squamous Cell Carcinoma by Regulating DNA Damage-Binding Protein 2. (PMID:32508265)
• USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling. (PMID:32511815)
• New paradigms of USP53 disease: normal GGT cholestasis, BRIC, cholangiopathy, and responsiveness to rifampicin. (PMID:32759993)
• Cholestasis Due to USP53 Deficiency. (PMID:33075013)
• Ubiquitin-specific protease 53 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. (PMID:33664230)
• Ubiquitin-specific peptidase 53 inhibits the occurrence and development of clear cell renal cell carcinoma through NF-kappaB pathway inactivation. (PMID:33973730)
• USP53 activated by H3K27 acetylation regulates cell viability, apoptosis and metabolism in esophageal carcinoma via the AMPK signaling pathway. (PMID:34919659)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp53b	ENSDARG00000076499
danio_rerio	USP53	ENSDARG00000078615
mus_musculus	Usp53	ENSMUSG00000039701
rattus_norvegicus	Usp53	ENSRNOG00000014660

Paralogs (1): USP54 (ENSG00000166348)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 53 — Q70EK8 (reviewed: Q70EK8)

Alternative names: Ubiquitin-specific peptidase 53

All UniProt accessions (5): A0A8I5KT61, A0A8J9FKG6, D6RF54, H0Y8Q1, Q70EK8

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase that mediates ‘Lys-63’-linked deubiquitination of tight junction proteins, such as MARVELD2 and LSR, and which is involved in the survival of auditory hair cells and hearing. Specifically cleaves ‘Lys-63’-linked polyubiquitin chains composed of at least 3 ubiquitin molecules, while it is not able to deubiquitinate substrates with shorter ubiquitin chains: recognizes ubiquitin chain in position S2 and catalyzes en bloc cleavage of polyubiquitin chains from substrate proteins. Probably acts by modulating the barrier properties and mechanical stability of tight junctions via deubiquitination of MARVELD2 and LSR.

Subunit / interactions. Interacts (via the C-terminal region) with the heterodimer TJP1:TJP2.

Subcellular location. Cell junction. Tight junction.

Tissue specificity. Expressed predominantly in skeletal muscle and heart.

Disease relevance. Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss (PFIC7) [MIM:619658] An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. Some PFIC7 patients develop hearing loss in childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase C19 family.

RefSeq proteins (16): NP_001358324, NP_001358325, NP_001358326, NP_001358327, NP_001358328, NP_001376587, NP_001376588, NP_001376589, NP_001376590, NP_001376591, NP_001376592, NP_001376593, NP_001376594, NP_001376595, NP_001376596, NP_061923 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR052398	Ubiquitin_hydrolase_53/54	Family

Pfam: PF00443

UniProt features (58 total): sequence variant 30, binding site 12, sequence conflict 5, compositionally biased region 4, region of interest 2, active site 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70EK8-F1	55.34	0.29

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): 41 (nucleophile); 301 (proton acceptor)

Ligand- & substrate-binding residues (12): 66; 68; 73; 76; 132; 144; 149; 152; 165; 168; 224; 228

Mutagenesis-validated functional residues (1):

Position	Phenotype
160	reduced ability to mediate cleavage of tri- and tetra-ubiquitin chains.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 215 (showing top): FISCHER_G1_S_CELL_CYCLE, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, CADWELL_ATG16L1_TARGETS_DN, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, CORRE_MULTIPLE_MYELOMA_UP, GOBP_RESPONSE_TO_AUDITORY_STIMULUS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_NEURON_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_SENSORY_PERCEPTION, ZHAN_MULTIPLE_MYELOMA_LB_UP, FISCHER_DREAM_TARGETS, LINDVALL_IMMORTALIZED_BY_TERT_UP, GOCC_CELL_CELL_JUNCTION

GO Biological Process (7): action potential (GO:0001508), sensory perception of sound (GO:0007605), response to auditory stimulus (GO:0010996), protein deubiquitination (GO:0016579), epithelial cell apoptotic process (GO:1904019), outer hair cell apoptotic process (GO:1905584), neuron apoptotic process (GO:0051402)

GO Molecular Function (5): metal ion binding (GO:0046872), K63-linked deubiquitinase activity (GO:0061578), cysteine-type deubiquitinase activity (GO:0004843), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
deubiquitinase activity	2
regulation of membrane potential	1
sensory perception of mechanical stimulus	1
response to mechanical stimulus	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
neuron apoptotic process	1
cation binding	1
cysteine-type peptidase activity	1
binding	1
catalytic activity	1
anchoring junction	1
apical junction complex	1
tight junction	1
cell junction	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP53	TJP2	Q9UDY2	675
USP53	USP50	Q70EL3	567
USP53	PAN2	Q504Q3	552
USP53	USP39	Q53GS9	504
USP53	USP48	Q86UV5	498
USP53	USPL1	Q5W0Q7	491
USP53	USP45	Q70EL2	482
USP53	USP49	Q70CQ1	464
USP53	USP38	Q8NB14	458
USP53	USP35	Q9P2H5	457
USP53	JOSD2	Q8TAC2	433
USP53	USP13	Q92995	432
USP53	USP44	Q9H0E7	431
USP53	AZGP1	P25311	430
USP53	USP5	P45974	428

IntAct

31 interactions, top by confidence:

A	B	Type	Score
USP53	CRK	psi-mi:“MI:0915”(physical association)	0.790
CRK	USP53	psi-mi:“MI:0915”(physical association)	0.790
CRKL	USP53	psi-mi:“MI:0915”(physical association)	0.560
SAMD4B	USP53	psi-mi:“MI:0915”(physical association)	0.560
IREB2	USP53	psi-mi:“MI:0915”(physical association)	0.370
USP53	NECTIN2	psi-mi:“MI:0915”(physical association)	0.370
TRAF2	USP53	psi-mi:“MI:0915”(physical association)	0.370
USP53	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
USP53	CRK	psi-mi:“MI:0915”(physical association)	0.000
USP53	CRKL	psi-mi:“MI:0915”(physical association)	0.000
USP53	SAMD4B	psi-mi:“MI:0915”(physical association)	0.000
USP53		psi-mi:“MI:0915”(physical association)	0.000
USP53	GRB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (154): USP53 (Two-hybrid), USP53 (Two-hybrid), ZEB1 (Affinity Capture-Western), USP53 (Affinity Capture-Western), USP53 (Affinity Capture-RNA), USP53 (Affinity Capture-RNA), USP53 (Reconstituted Complex), CRK (Two-hybrid), USP53 (Two-hybrid), EZH2 (Affinity Capture-Western), USP53 (Affinity Capture-Western), USP53 (Proximity Label-MS), CTNNB1 (Affinity Capture-Western), USP53 (Proximity Label-MS), USP53 (Proximity Label-MS)

ESM2 similar proteins: A0A509AC44, A2BDC9, A6NM62, A6ZQG7, B4HWI2, B7TB45, O35607, O61643, P25435, P28003, P28466, P36168, P38742, P38970, P42519, P50104, P53253, P56715, P70041, P85828, Q00805, Q07G34, Q09101, Q12202, Q13873, Q1W7Q6, Q24741, Q25132, Q26307, Q3HXX8, Q3HXX9, Q3HXY9, Q3HXZ1, Q53TS8, Q59Y11, Q5RA75, Q5RJX8, Q5YF90, Q6GP17, Q6PCB5

Diamond homologs: P15975, Q6IE24, Q70EK8, Q70EL1, Q8BL06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	19
Uncertain significance	136
Likely benign	45
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1328227	NM_001371395.1(USP53):c.951del (p.Phe317fs)	Pathogenic
1328232	NM_001371395.1(USP53):c.725C>T (p.Pro242Leu)	Pathogenic
1328233	NM_001371395.1(USP53):c.510del (p.Ser171fs)	Pathogenic
1686292	NM_001371395.1(USP53):c.1687del (p.Ser563fs)	Pathogenic
2054558	NM_001371395.1(USP53):c.108del (p.Gly37fs)	Pathogenic
2062610	NM_001371395.1(USP53):c.21dup (p.Arg8fs)	Pathogenic
2066808	NM_001371395.1(USP53):c.1948dup (p.Ile650fs)	Pathogenic
2075241	NM_001371395.1(USP53):c.2068dup (p.Ser690fs)	Pathogenic
2692225	NM_001371395.1(USP53):c.153G>A (p.Trp51Ter)	Pathogenic
3370325	NM_001371395.1(USP53):c.1069dup (p.Ser357fs)	Pathogenic
3572956	NM_001371395.1(USP53):c.1219A>T (p.Lys407Ter)	Pathogenic
4701410	NM_001371395.1(USP53):c.209del (p.Gly70fs)	Pathogenic
694273	NM_001371395.1(USP53):c.1012C>T (p.Arg338Ter)	Pathogenic
694473	NM_001371395.1(USP53):c.169C>T (p.Arg57Ter)	Pathogenic
694474	NM_001371395.1(USP53):c.297G>T (p.Arg99Ser)	Pathogenic
694476	NM_001371395.1(USP53):c.569+2T>C	Pathogenic
694477	NM_001371395.1(USP53):c.583del (p.Arg195fs)	Pathogenic
694478	NM_001371395.1(USP53):c.834_835dup (p.Val279fs)	Pathogenic
694481	NM_001371395.1(USP53):c.1558C>T (p.Arg520Ter)	Pathogenic
1333554	NM_001371395.1(USP53):c.205C>T (p.Gln69Ter)	Likely pathogenic
1526033	NM_001371395.1(USP53):c.158T>A (p.Leu53Ter)	Likely pathogenic
1526171	NM_001371395.1(USP53):c.331C>T (p.Arg111Ter)	Likely pathogenic
1705415	NM_001371395.1(USP53):c.972+3_972+6del	Likely pathogenic
1705494	NM_001371395.1(USP53):c.973-1G>A	Likely pathogenic
1705629	NM_001371395.1(USP53):c.78_79dup (p.Ala27fs)	Likely pathogenic
2434496	NM_001371395.1(USP53):c.829del (p.Tyr277fs)	Likely pathogenic
2584943	NM_001371395.1(USP53):c.1295_1299del (p.Leu432fs)	Likely pathogenic
2585608	NM_001371395.1(USP53):c.822+1del	Likely pathogenic
2637328	NM_001371395.1(USP53):c.1636dup (p.Ile546fs)	Likely pathogenic
2671669	NM_001371395.1(USP53):c.237+1G>A	Likely pathogenic

SpliceAI

2868 predictions. Top by Δscore:

Variant	Effect	Δscore
4:119214068:A:AG	acceptor_gain	1.0000
4:119214069:G:GG	acceptor_gain	1.0000
4:119214069:GTTCC:G	acceptor_gain	1.0000
4:119214114:A:G	donor_gain	1.0000
4:119214221:GT:G	donor_gain	1.0000
4:119245400:G:GT	donor_gain	1.0000
4:119248743:CCCA:C	acceptor_loss	1.0000
4:119248744:CCA:C	acceptor_loss	1.0000
4:119248745:CA:C	acceptor_loss	1.0000
4:119248746:A:AG	acceptor_gain	1.0000
4:119248746:AGAC:A	acceptor_gain	1.0000
4:119248747:G:GA	acceptor_gain	1.0000
4:119248747:GAC:G	acceptor_gain	1.0000
4:119248747:GACG:G	acceptor_gain	1.0000
4:119248878:GCTTT:G	donor_gain	1.0000
4:119248879:CTTT:C	donor_gain	1.0000
4:119248880:TTT:T	donor_gain	1.0000
4:119248880:TTTG:T	donor_loss	1.0000
4:119248881:TT:T	donor_gain	1.0000
4:119248882:TG:T	donor_loss	1.0000
4:119248883:G:GG	donor_gain	1.0000
4:119248883:GTAAG:G	donor_loss	1.0000
4:119248884:TA:T	donor_loss	1.0000
4:119248885:A:AT	donor_loss	1.0000
4:119256355:AACAG:A	donor_loss	1.0000
4:119256358:AGG:A	donor_loss	1.0000
4:119256359:GGTG:G	donor_loss	1.0000
4:119256360:G:GA	donor_loss	1.0000
4:119256361:T:G	donor_loss	1.0000
4:119256438:T:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10000726 (4:119289609 G>A), RS1000100275 (4:119238624 A>T), RS1000119215 (4:119225619 G>A), RS10001498 (4:119249522 G>A,T), RS1000167836 (4:119246149 CTG>C), RS1000178171 (4:119265246 A>G), RS1000186764 (4:119215584 A>T), RS1000212942 (4:119269214 A>G), RS1000270183 (4:119268688 G>A), RS1000296787 (4:119253100 A>C), RS1000323168 (4:119281473 T>C,G), RS1000397030 (4:119262164 T>G), RS1000424771 (4:119222634 T>C), RS1000498892 (4:119228923 T>C,G), RS1000503078 (4:119236358 A>G)

Disease associations

OMIM: gene MIM:617431 | disease phenotypes: MIM:619658

GenCC curated gene-disease

Disease	Classification	Inheritance
cholestasis	Strong	Autosomal recessive
cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Strong	Autosomal recessive

Mondo (3): cholestasis, progressive familial intrahepatic, 7, with or without hearing loss (MONDO:0030503), premature menopause (MONDO:0001119), cholestasis (MONDO:0001751)

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000952	Jaundice
HP:0000989	Pruritus
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001744	Splenomegaly
HP:0002901	Hypocalcemia
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0011463	Childhood onset
HP:0012852	Hepatic bridging fibrosis
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0410053	Elevated circulating gamma-aminobutyric acid concentration

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST008129_15	Body mass index	2.000000e-09
GCST010002_14	Refractive error	5.000000e-18
GCST90000025_282	Appendicular lean mass	7.000000e-22
GCST90020024_677	A body shape index	4.000000e-11
GCST90020025_609	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_1836	Waist-hip index	5.000000e-11
GCST90020029_752	Waist circumference adjusted for body mass index	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002779	Cholestasis	C06.130.120.135
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	3
bisphenol A	increases expression, decreases expression, decreases methylation, affects cotreatment	3
(+)-JQ1 compound	increases expression	3
Cisplatin	decreases expression, increases expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Folic Acid	affects cotreatment, increases expression, affects expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
diallyl trisulfide	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Bortezomib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Ethanol	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0SM	Ubigene HeLa USP53 KO	Cancer cell line	Female
CVCL_TX08	HAP1 USP53 (-) 1	Cancer cell line	Male
CVCL_TX09	HAP1 USP53 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01373918	PHASE4	TERMINATED	Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders
NCT01585935	PHASE4	COMPLETED	Preventing Cholestasis Using SMOFLipid®
NCT01998620	PHASE4	UNKNOWN	Efficacy and Safety of S-adenosyl-L-methionine in Treatment of Chronic Hepatitis B Patients With Cholestasis
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT00058890	PHASE3	COMPLETED	Gabapentin to Treat Itch in Patients With Liver Disease
NCT01194063	PHASE3	COMPLETED	Use of Omegaven Fish Oil Emulsion for Parenteral Nutrition Associated Liver Disease in Infants and Children
NCT02357576	PHASE3	COMPLETED	Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD
NCT02663453	PHASE3	COMPLETED	Effectiveness of Multicomponent Lipid Emulsion in Preterm Infants Requiring Parenteral Nutrition
NCT03662282	PHASE3	COMPLETED	Omegaven as Alternative Parenteral Fat Nutrition
NCT04167358	PHASE3	ACTIVE_NOT_RECRUITING	Linerixibat Long-term Safety, and Tolerability Study
NCT04309773	PHASE3	UNKNOWN	Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00004315	PHASE2	UNKNOWN	Phase II Pilot Study to Compare the Bioavailability of Buffered, Enteric-Coated Ursodiol With Unmodified Ursodiol for Chronic Cholestatic Liver Disease and Cystic Fibrosis-Associated Liver Disease
NCT00080236	PHASE2	COMPLETED	Safety and Efficacy Study of a Caspase Inhibitor in Patients Undergoing Liver Transplantation
NCT00816348	PHASE2	TERMINATED	Compassionate Use of Omegaven IV Fat Emulsion
NCT00826020	PHASE2	COMPLETED	Evaluation of Omegaven™ Parenteral Nutrition in Patients With Total Parenteral Nutrition (TPN)-Induced Cholestasis
NCT00969332	PHASE2	TERMINATED	A Safety and Efficacy Study to Determine if Giving Intravenous Fish Oil Helps Children With Liver Disease
NCT01739517	PHASE2	UNKNOWN	Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease
NCT02420496	PHASE2	WITHDRAWN	Enteral Fish Oil is Superior to Ursodeoxycholic Acid (UDCA) and Placebo for the Treatment of Cholestasis in Infants
NCT02966834	PHASE2	COMPLETED	Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants With Primary Biliary Cholangitis
NCT03586674	PHASE2	COMPLETED	Fibrates in Pediatric Cholestasis
NCT04604652	PHASE2	COMPLETED	Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00512629	PHASE1	COMPLETED	Cholestasis Prevention: Efficacy of IV Fish Oil
NCT01879735	PHASE1	COMPLETED	Biliary Excretion of Conjugated Bile Acids in Humans Measured by 11C-cholylsarcosine PET/CT
NCT02267707	PHASE1	TERMINATED	Pharmacokinetic and Safety Study of Nab®-Paclitaxel (ABI-007) Plus Gemcitabine in Subjects With Advanced Pancreatic Cancer Who Have Cholestatic Hyperbilirubinemia
NCT02801981	PHASE1	COMPLETED	Dose-escalation Study of GSK2330672 in Japanese Healthy Male Volunteers
NCT03992014	PHASE1	COMPLETED	Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat
NCT04053023	PHASE1	COMPLETED	Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects