USP45

Summary

USP45 (ubiquitin specific peptidase 45, HGNC:20080) is a protein-coding gene on chromosome 6q16.2, encoding Ubiquitin carboxyl-terminal hydrolase 45 (Q70EL2). Catalyzes the deubiquitination of SPDL1.

The protein encoded by this gene is a deubiquitylase that binds ERCC1, the catalytic subunit of the XPF-ERCC1 DNA repair endonuclease. This endonuclease is a critical regulator of DNA repair processes, and the deubiquitylase activity of the encoded protein is important for maintaining the DNA repair ability of XPF-ERCC1.

Source: NCBI Gene 85015 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leber congenital amaurosis 19 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 158 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• MANE Select transcript: NM_001346022

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20080
Approved symbol	USP45
Name	ubiquitin specific peptidase 45
Location	6q16.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC14793
Ensembl gene	ENSG00000123552
Ensembl biotype	protein_coding
OMIM	618439
Entrez	85015

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000327681, ENST00000329966, ENST00000369232, ENST00000369233, ENST00000472914, ENST00000496090, ENST00000496518, ENST00000500704, ENST00000506871, ENST00000507717, ENST00000508908, ENST00000511403, ENST00000513344, ENST00000917068, ENST00000917069, ENST00000917070

RefSeq mRNA: 13 — MANE Select: NM_001346022 NM_001080481, NM_001346021, NM_001346022, NM_001346023, NM_001346024, NM_001346025, NM_001346026, NM_001346027, NM_001346028, NM_001346029, NM_001346030, NM_001346033, NM_032929

CCDS: CCDS34501, CCDS87419

Canonical transcript exons

ENST00000500704 — 18 exons

Exon	Start	End
ENSE00001410872	99515392	99515423
ENSE00001449266	99482753	99482883
ENSE00001986720	99432325	99435846
ENSE00002047060	99468537	99468618
ENSE00003488944	99508610	99508782
ENSE00003492448	99488200	99488295
ENSE00003511395	99488681	99488820
ENSE00003513601	99464604	99464747
ENSE00003514558	99437246	99437399
ENSE00003555027	99439769	99439855
ENSE00003578373	99503765	99503865
ENSE00003601398	99466672	99466763
ENSE00003605683	99507428	99507531
ENSE00003618719	99476143	99476230
ENSE00003632413	99510121	99510230
ENSE00003648877	99445797	99446463
ENSE00003657792	99465080	99465136
ENSE00003690231	99443565	99443662

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 91.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5413 / max 162.6621, expressed in 1698 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74813	8.1030	1686
74812	0.4217	186
74811	0.0166	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	91.32	gold quality
secondary oocyte	CL:0000655	89.92	gold quality
epithelial cell of pancreas	CL:0000083	86.80	gold quality
oocyte	CL:0000023	86.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.50	gold quality
cerebellar hemisphere	UBERON:0002245	84.17	gold quality
cerebellar cortex	UBERON:0002129	84.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.99	gold quality
cerebellum	UBERON:0002037	83.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.48	gold quality
rectum	UBERON:0001052	82.38	gold quality
islet of Langerhans	UBERON:0000006	81.22	gold quality
gastrocnemius	UBERON:0001388	81.18	gold quality
gall bladder	UBERON:0002110	80.83	gold quality
muscle of leg	UBERON:0001383	80.72	gold quality
adrenal tissue	UBERON:0018303	79.93	gold quality
stromal cell of endometrium	CL:0002255	79.90	gold quality
pancreas	UBERON:0001264	79.88	gold quality
corpus callosum	UBERON:0002336	79.77	gold quality
smooth muscle tissue	UBERON:0001135	79.60	gold quality
right ovary	UBERON:0002118	79.41	gold quality
body of pancreas	UBERON:0001150	79.36	gold quality
descending thoracic aorta	UBERON:0002345	79.14	gold quality
left ovary	UBERON:0002119	79.10	gold quality
omental fat pad	UBERON:0010414	78.80	gold quality
left coronary artery	UBERON:0001626	78.78	gold quality
vermiform appendix	UBERON:0001154	78.77	gold quality
tibial artery	UBERON:0007610	78.77	gold quality
popliteal artery	UBERON:0002250	78.76	gold quality
peritoneum	UBERON:0002358	78.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.72

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• these results establish USP45 as a new regulator of XPF-ERCC1 crucial for efficient DNA repair (PMID:25538220)
• Using mass spectrometry this study identified CCDC99 as a new target of USP45. The data showed that CCDC99 and USP45 are part of the same complex and that their interaction specifically depends on the catalytic activity of USP45. (PMID:30258100)
• Our study implicates that biallelic mutations in USP45 are associated with the occurrence of LCA. Moreover, our results indicate that USP45 is indispensable to the maintenance of photoreceptor function. (PMID:30573563)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp45	ENSDARG00000075013
mus_musculus	Usp45	ENSMUSG00000040455
rattus_norvegicus	Usp45	ENSRNOG00000008688

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), 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 45 — Q70EL2 (reviewed: Q70EL2)

Alternative names: Deubiquitinating enzyme 45, Ubiquitin thioesterase 45, Ubiquitin-specific-processing protease 45

All UniProt accessions (9): D6RBV3, D6RC01, D6RE98, E2QRF0, Q70EL2, H0Y8J5, H0Y8Q0, H0Y986, H0YA21

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the deubiquitination of SPDL1. Plays a role in the repair of UV-induced DNA damage via deubiquitination of ERCC1, promoting its recruitment to DNA damage sites. May be involved in the maintenance of photoreceptor function. May play a role in normal retinal development. Plays a role in cell migration.

Subunit / interactions. Interacts with ERCC1. The catalytically active form interacts with SPDL1.

Subcellular location. Photoreceptor inner segment. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed. High expression is detected in the cerebellum. In the eye, it is expressed at high levels in the optic nerve, sclera and retina, with relatively low levels in the choroid, lens and retinal pigment epithelium.

Disease relevance. Leber congenital amaurosis 19 (LCA19) [MIM:618513] A form of Leber congenital amaurosis, a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. LCA19 is an autosomal recessive form characterized by reduced vision in early childhood and severely reduced responses of both rods and cones. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase C19 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q70EL2-1	1	yes
Q70EL2-2	2
Q70EL2-3	3

RefSeq proteins (13): NP_001073950, NP_001332950, NP_001332951, NP_001332952, NP_001332953, NP_001332954, NP_001332955, NP_001332956, NP_001332957, NP_001332958, NP_001332959, NP_001332962, NP_116318 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR001607	Znf_UBP	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050185	Ub_carboxyl-term_hydrolase	Family

Pfam: PF00443, PF02148

UniProt features (46 total): binding site 12, splice variant 5, sequence variant 5, mutagenesis site 5, modified residue 4, region of interest 4, sequence conflict 3, compositionally biased region 3, active site 2, chain 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70EL2-F1	66.28	0.27

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): 199 (nucleophile); 746 (proton acceptor)

Ligand- & substrate-binding residues (12): 38; 40; 62; 65; 85; 88; 93; 101; 105; 114; 127; 130

Post-translational modifications (4): 28, 29, 508, 526

Mutagenesis-validated functional residues (5):

Position	Phenotype
25	significant reduction in interaction with ercc1. complete loss of ability to interact with and deubiquitinate ercc1; whe
26	significant reduction in interaction with ercc1. complete loss of ability to interact with and deubiquitinate ercc1; whe
27	significant reduction in interaction with ercc1.
37	loss of protein expression.
199	catalytically inactive. loss of ability to deubiquitinate ercc1. loss of interaction with spdl1 and ability to deubiquit

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5696395	Formation of Incision Complex in GG-NER

MSigDB gene sets: 177 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, XU_GH1_AUTOCRINE_TARGETS_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_NUCLEOTIDE_EXCISION_REPAIR, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_RETINA_HOMEOSTASIS, REACTOME_DNA_REPAIR, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE

GO Biological Process (7): neural retina development (GO:0003407), DNA repair (GO:0006281), proteolysis (GO:0006508), cell migration (GO:0016477), protein deubiquitination (GO:0016579), photoreceptor cell maintenance (GO:0045494), global genome nucleotide-excision repair (GO:0070911)

GO Molecular Function (7): cysteine-type deubiquitinase activity (GO:0004843), zinc ion binding (GO:0008270), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): photoreceptor inner segment (GO:0001917), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
anatomical structure development	1
retina development in camera-type eye	1
DNA metabolic process	1
DNA damage response	1
protein metabolic process	1
cell motility	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
retina homeostasis	1
multicellular organismal process	1
nucleotide-excision repair	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
transition metal ion binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP45	USP39	Q53GS9	611
USP45	FAXC	Q5TGI0	552
USP45	OTUB1	Q96FW1	527
USP45	USP13	Q92995	507
USP45	OTUB2	Q96DC9	500
USP45	KLHL7	Q8IXQ5	500
USP45	USP28	Q96RU2	484
USP45	USP53	Q70EK8	482
USP45	USP14	P54578	470
USP45	PAN2	Q504Q3	461
USP45	USP5	P45974	459
USP45	COQ3	Q9NZJ6	458
USP45	OTUD6B	Q8N6M0	456
USP45	USP54	Q70EL1	450
USP45	PNISR	Q8TF01	438

IntAct

5 interactions, top by confidence:

A	B	Type	Score
USP45	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
USP45	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
USP45	RTCA	psi-mi:“MI:0914”(association)	0.350
CSNK2B	OSBPL8	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): USP45 (Affinity Capture-MS), USP45 (Affinity Capture-MS), USP45 (Affinity Capture-MS), USP45 (Affinity Capture-MS), USP45 (Affinity Capture-MS), USP45 (Affinity Capture-MS), SLX4 (Affinity Capture-Western), ERCC1 (Affinity Capture-Western), ERCC4 (Affinity Capture-Western), USP45 (Affinity Capture-Western), ERCC1 (Two-hybrid), USP45 (Two-hybrid), ERCC1 (Biochemical Activity), MYH10 (Affinity Capture-MS), RBMX (Affinity Capture-MS)

ESM2 similar proteins: A1A5G2, A4FUN7, A4IF63, A5WWB0, A6H8I0, A6NNY8, C0HB46, D2HBJ8, D3ZQG6, E1C1R4, F7H9X2, O24454, P0C8Z3, P15209, P24786, P34547, P42694, Q03351, Q0V9G5, Q16288, Q16620, Q504Q3, Q52KZ6, Q5DU02, Q5R7T2, Q5U252, Q5XGZ2, Q63604, Q6DCJ1, Q6DFV5, Q6GNI6, Q6IE70, Q6NTR6, Q6P9L4, Q70CQ1, Q70EL2, Q7ZUM8, Q8BGF7, Q8BY87, Q8CEG8

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

2 interactions.

A	Effect	B	Mechanism
USP45	“up-regulates activity”	ERCC4/ERCC1	deubiquitination
USP45	“up-regulates activity”	SPDL1	deubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	107
Likely benign	12
Benign	12

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
599555	NM_001346022.3(USP45):c.1990G>T (p.Gly664Ter)	Pathogenic
638072	NM_001346022.3(USP45):c.935G>A (p.Arg312Gln)	Pathogenic
2443296	NM_001346022.3(USP45):c.1327C>T (p.Arg443Ter)	Likely pathogenic
3901119	NM_001346022.3(USP45):c.931_932del (p.Lys311fs)	Likely pathogenic
4849450	NM_001346022.3(USP45):c.878_881del (p.Asp293fs)	Likely pathogenic

SpliceAI

3832 predictions. Top by Δscore:

Variant	Effect	Δscore
6:99437285:T:A	donor_gain	1.0000
6:99437302:A:AC	donor_gain	1.0000
6:99437303:C:CC	donor_gain	1.0000
6:99437396:CATT:C	acceptor_gain	1.0000
6:99437398:TT:T	acceptor_gain	1.0000
6:99437400:C:CC	acceptor_gain	1.0000
6:99437403:T:C	acceptor_gain	1.0000
6:99437403:T:TC	acceptor_gain	1.0000
6:99443658:CTTTT:C	acceptor_gain	1.0000
6:99443663:C:CC	acceptor_gain	1.0000
6:99443667:A:C	acceptor_gain	1.0000
6:99464598:TCTTA:T	donor_loss	1.0000
6:99464599:CTTA:C	donor_loss	1.0000
6:99464600:TTACC:T	donor_loss	1.0000
6:99464601:TACC:T	donor_loss	1.0000
6:99464602:ACC:A	donor_loss	1.0000
6:99465078:AC:A	donor_gain	1.0000
6:99465079:CC:C	donor_gain	1.0000
6:99465138:T:C	acceptor_gain	1.0000
6:99465138:T:TC	acceptor_gain	1.0000
6:99468619:C:CC	acceptor_gain	1.0000
6:99476137:CCTGA:C	donor_loss	1.0000
6:99476138:CTGA:C	donor_loss	1.0000
6:99476139:TGAC:T	donor_loss	1.0000
6:99476140:GAC:G	donor_loss	1.0000
6:99476142:C:CT	donor_loss	1.0000
6:99476227:TGCC:T	acceptor_gain	1.0000
6:99476228:GCC:G	acceptor_gain	1.0000
6:99476229:CC:C	acceptor_gain	1.0000
6:99476229:CCCTG:C	acceptor_gain	1.0000

AlphaMissense

5395 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:99466689:A:G	C364R	0.999
6:99443632:G:T	A669D	0.998
6:99445901:A:G	L624P	0.998
6:99435733:A:C	Y810D	0.997
6:99445851:A:G	C641R	0.997
6:99466687:A:C	C364W	0.997
6:99466688:C:G	C364S	0.997
6:99466689:A:T	C364S	0.997
6:99437372:A:C	Y730D	0.996
6:99439787:G:C	F714L	0.996
6:99439787:G:T	F714L	0.996
6:99439789:A:G	F714L	0.996
6:99443617:A:G	L674P	0.996
6:99443633:C:G	A669P	0.996
6:99445891:A:C	F627L	0.996
6:99445891:A:T	F627L	0.996
6:99445893:A:G	F627L	0.996
6:99466688:C:T	C364Y	0.996
6:99466712:C:T	G356D	0.996
6:99468617:C:G	R312P	0.996
6:99435811:A:G	W784R	0.995
6:99435811:A:T	W784R	0.995
6:99439803:A:G	L709P	0.995
6:99443602:G:C	P679R	0.995
6:99443623:T:G	Q672P	0.995
6:99445841:C:G	C644S	0.995
6:99445842:A:T	C644S	0.995
6:99465099:A:G	L382P	0.995
6:99443593:A:G	L682P	0.994
6:99443602:G:T	P679Q	0.994

dbSNP variants (sampled 300 via entrez): RS1000008548 (6:99461044 G>A), RS1000080320 (6:99460682 T>C), RS1000083214 (6:99450279 AC>A), RS1000129452 (6:99432458 A>G), RS1000160564 (6:99432102 T>C), RS1000184274 (6:99480116 T>C), RS1000195939 (6:99489211 A>C,G), RS1000198488 (6:99486265 C>T), RS1000205463 (6:99440755 T>C), RS1000232806 (6:99483052 C>G), RS1000308506 (6:99439355 A>G), RS1000353110 (6:99453893 G>C), RS1000393833 (6:99462252 A>C), RS1000449349 (6:99492619 T>C), RS1000452997 (6:99505129 G>A)

Disease associations

OMIM: gene MIM:618439 | disease phenotypes: MIM:618513, MIM:601086, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis 19	Strong	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant

Mondo (6): inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis 19 (MONDO:0032794), laterality defects, autosomal dominant (MONDO:0010991), Leber congenital amaurosis (MONDO:0018998), optic atrophy (MONDO:0003608), retinal disorder (MONDO:0005283)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Visceral heterotaxy (Orphanet:450), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000563	Keratoconus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000654	Decreased light- and dark-adapted electroretinogram amplitude
HP:0000729	Autistic behavior
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001483	Eye poking
HP:0002084	Encephalocele
HP:0002269	Abnormality of neuronal migration
HP:0004374	Hemiplegia/hemiparesis
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis
HP:0007703	Abnormal retinal pigmentation
HP:0007843	Attenuation of retinal blood vessels
HP:0012426	Optic disc drusen
HP:0012795	Abnormal optic disc morphology
HP:0030211	Slow pupillary light response
HP:0030466	Abnormal full-field electroretinogram

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005024_24	Pursuit maintenance gain	8.000000e-06
GCST007118_1	Erectile dysfunction	2.000000e-37

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C563391	Laterality Defects, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630841 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases expression, affects cotreatment, increases abundance, increases oxidation	3
Valproic Acid	decreases methylation, increases expression	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Gallic Acid	decreases expression	1
Manganese	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	increases expression, increases abundance	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
CHEMBL4605989	Binding	Inhibition of USP45 (unknown origin)	Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with In Vivo Antitumor Activity. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TW99	HAP1 USP45 (-) 1	Cancer cell line	Male
CVCL_TX00	HAP1 USP45 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT03913143	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT00749957	PHASE1/PHASE2	COMPLETED	Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
NCT01208389	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
NCT01496040	PHASE1/PHASE2	COMPLETED	Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65
NCT02781480	PHASE1/PHASE2	COMPLETED	Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)
NCT03913130	PHASE1/PHASE2	TERMINATED	Extension Study to Study PQ-110-001 (NCT03140969)
NCT03920007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D
NCT05203939	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
NCT05906953	PHASE1/PHASE2	RECRUITING	Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
NCT06088992	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02575430	Not specified	COMPLETED	Natural History Study in Inherited Retinal Disease Subjects Caused by Mutations in RPE65 or LRAT
NCT02714816	Not specified	COMPLETED	Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65
NCT02946879	Not specified	COMPLETED	Long-Term Follow-Up Gene Therapy Study for Leber Congenital Amaurosis OPTIRPE65 (Retinal Dystrophy Associated With Defects in RPE65)
NCT02970266	Not specified	COMPLETED	Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families.
NCT07026565	Not specified	NOT_YET_RECRUITING	Psychotherapy Group for Parents of Children With LCA
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001