TOPORS

Summary

TOPORS (TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase, HGNC:21653) is a protein-coding gene on chromosome 9p21.1, encoding E3 ubiquitin-protein ligase Topors (Q9NS56). Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase.

This gene encodes a nuclear protein which is serine and arginine rich, and contains a RING-type zinc finger domain. It is highly expressed in the testis, and functions as an ubiquitin-protein E3 ligase. Mutations in this gene are associated with retinitis pigmentosa type 31. Alternatively spliced transcript variants, encoding different isoforms, have been observed for this locus.

Source: NCBI Gene 10210 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TOPORS-related retinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 704 total — 6 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 85
• MANE Select transcript: NM_005802

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21653
Approved symbol	TOPORS
Name	TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase
Location	9p21.1
Locus type	gene with protein product
Status	Approved
Aliases	TP53BPL, LUN
Ensembl gene	ENSG00000197579
Ensembl biotype	protein_coding
OMIM	609507
Entrez	10210

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000360538, ENST00000379858, ENST00000947237

RefSeq mRNA: 2 — MANE Select: NM_005802 NM_001195622, NM_005802

CCDS: CCDS56566, CCDS6527

Canonical transcript exons

ENST00000360538 — 3 exons

Exon	Start	End
ENSE00001091724	32540544	32544326
ENSE00001091728	32550774	32550968
ENSE00003844059	32552434	32552586

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6350 / max 147.2130, expressed in 1755 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100392	3.4781	1544
100387	2.7048	964
100391	2.4953	1425
100388	1.2008	427
100390	0.4865	216
100389	0.2694	109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.46	gold quality
calcaneal tendon	UBERON:0003701	94.21	gold quality
sperm	CL:0000019	93.60	gold quality
oocyte	CL:0000023	92.70	gold quality
male germ cell	CL:0000015	91.05	gold quality
cauda epididymis	UBERON:0004360	90.94	gold quality
corpus epididymis	UBERON:0004359	89.76	gold quality
caput epididymis	UBERON:0004358	89.23	gold quality
choroid plexus epithelium	UBERON:0003911	89.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.05	gold quality
buccal mucosa cell	CL:0002336	89.04	gold quality
ventricular zone	UBERON:0003053	88.62	gold quality
trabecular bone tissue	UBERON:0002483	88.25	gold quality
jejunal mucosa	UBERON:0000399	88.08	gold quality
blood vessel layer	UBERON:0004797	87.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.87	gold quality
seminal vesicle	UBERON:0000998	87.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.29	gold quality
tendon	UBERON:0000043	86.75	gold quality
oral cavity	UBERON:0000167	86.73	gold quality
bone marrow	UBERON:0002371	86.71	gold quality
lower lobe of lung	UBERON:0008949	86.50	gold quality
superficial temporal artery	UBERON:0001614	86.29	gold quality
islet of Langerhans	UBERON:0000006	86.09	gold quality
cartilage tissue	UBERON:0002418	86.06	gold quality
pigmented layer of retina	UBERON:0001782	86.03	gold quality
cerebellar vermis	UBERON:0004720	85.93	gold quality
palpebral conjunctiva	UBERON:0001812	85.43	gold quality
endometrium	UBERON:0001295	85.30	gold quality
ganglionic eminence	UBERON:0004023	85.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05
E-GEOD-100618	no	1789.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting TOPORS, 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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 24)

• Topors, a p53 and topoisomerase I binding protein, interacts with the adeno-associated virus (AAV-2) Rep78/68 proteins and enhances AAV-2 gene expression (PMID:11842245)
• topors localizes in punctate nuclear regions associated with PML protein nuclear bodies. (PMID:12083797)
• Multiple SUMO-1 modified forms of Topors could be detected after cotransfection of exogenous SUMO-1 and Topors induced the colocalization of a YFP tagged SUMO-1 protein in a speckled pattern in the nucleus. (PMID:14516784)
• topors functions as a negative regulator of cell growth, and possibly as a tumor suppressor (PMID:15107820)
• topors has a role as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53 (PMID:15247280)
• Results show that the ATR/checkpoint kinase 1 pathway plays a predominant role in the response to topoisomerase I inhibitors in carcinoma cells. (PMID:15699047)
• topors mediates p53-dependent cellular responses induced by DNA damage, suggesting its physiological role as a tumor suppressor (PMID:15735665)
• Data show that Topors enhances the conjugation of the small ubiquitin-like modifier 1 (SUMO-1) to p53 in vivo and in a reconstituted in vitro system. (PMID:16122737)
• The findings suggest that TOPORS may function as a tumor suppressor by regulating mSin3A and other proteins involved in chromatin modification. (PMID:17803295)
• Mutations in the gene for topoisomerase I-binding RS protein (TOPORS) in patients with autosomal dominant retinitis pigmentosa (adRP) linked to chromosome 9p21.1 (locus RP31), is reported. (PMID:17924349)
• Topors enhances the formation of high-molecular weight SUMO-1 conjugates of TOP1 in a reconstituted in vitro system and also in human osteosarcoma cells (PMID:17976381)
• NKX3.1 can be ubiquitinated by TOPORS in vitro and in vivo, and overexpression of TOPORS leads to NKX3.1 proteasomal degradation in prostate cancer cells (PMID:18077445)
• Point mutations and small insertions or deletions in TOPORS cause approximately 1% of autosomal dominant retinitis pigmentosa. (PMID:18509552)
• We present a novel mutation in the TOPORS gene co-segregating with a distinct phenotype of adPRD in a large Norwegian family. (PMID:19183411)
• Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP). (PMID:19373681)
• Plk1 modulates Topors activity in suppressing p53 function (PMID:19473992)
• Polo-like kinase 1 (Plk1)-associated phosphorylation of Topors at S718 is essential for nocodazole-induced degradation of Topors. (PMID:19821153)
• In photoreceptors, TOPORS localizes primarily to the basal bodies of connecting cilium and in the centrosomes. (PMID:21159800)
• Disturbed flow induces peroxynitrite production and binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy). (PMID:21624951)
• Data suggest that TOPORS plays key role in turnover of H2AX (H2A histone family, member X protein) depending on the type of oxidative stress/DNA damage; TOPORS may act as an E3 ubiquitin ligase for histones. (PMID:22972498)
• P26s4 Associates with the C-Terminal Region of TOPORS. (PMID:26872363)
• A novel mutation of the TOPORS gene was identified, c.2539C>T p.(Arg847Ter), resulting in a premature termination codon and suggesting haploinsufficiency as the pathological mechanism. (PMID:28453362)
• Mutations of TOPORS identified in families with retinitis pigmentosa. (PMID:35254173)
• Autosomal Dominant Retinitis Pigmentosa-Associated TOPORS Protein Truncating Variants Are Exclusively Located in the Region of Amino Acid Residues 807 to 867. (PMID:35579903)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	toporsa	ENSDARG00000037260
		ENSDARG00000105028
mus_musculus	Topors	ENSMUSG00000036822
rattus_norvegicus	Topors	ENSRNOG00000006485
drosophila_melanogaster	Topors	FBGN0267351

Protein

Protein identifiers

E3 ubiquitin-protein ligase Topors — Q9NS56 (reviewed: Q9NS56)

Alternative names: RING-type E3 ubiquitin transferase Topors, SUMO1-protein E3 ligase Topors, Topoisomerase I-binding RING finger protein, Topoisomerase I-binding arginine/serine-rich protein, Tumor suppressor p53-binding protein 3

All UniProt accessions (1): Q9NS56

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates p53/TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA damage-induced cell death through IKBKE sumoylation.

Subunit / interactions. Interacts with PARK7/DJ-1. Interacts with TOP1. Interacts with p53/TP53; can both ubiquitinate and sumoylate p53/TP53. Interacts with the SUMO1 conjugating enzyme UBE2I. Interacts with SUMO1. Interacts with NKX3-1; polyubiquitinates NKX3-1 and induces its proteasomal degradation. Interacts with SIN3A; sumoylates SIN3A. Interacts with IKBKE; induced by DNA damage.

Subcellular location. Nucleus. PML body.

Tissue specificity. Expressed at highest levels in testis and at lower levels in adrenal gland, bone marrow, brain, colon, heart, kidney, liver, muscle, ovary, pancreas, placenta, prostate, skeletal muscle, skin, small intestine, spleen, stomach, testis, thymus, thyroid and uterus. Expressed in the alveolar epithelium of the lung. Expression is commonly decreased in colon adenocarcinomas and lung cancers.

Post-translational modifications. Phosphorylation at Ser-98 regulates the E3 ubiquitin-protein ligase activity but not the SUMO1-protein ligase activity. Phosphorylation at Ser-718 increases the E3 ubiquitin-protein ligase activity versus the SUMO1-protein ligase activity resulting in increased p53/TP53 ubiquitination and degradation. Sumoylated.

Disease relevance. Retinitis pigmentosa 31 (RP31) [MIM:609923] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry.

Induction. By genotoxic agents such as cisplatin and camptothecin.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NS56-1	1, LUN-1	yes
Q9NS56-2	2, LUN-2

RefSeq proteins (2): NP_001182551, NP_005793* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR018957	Znf_C3HC4_RING-type	Domain
IPR058745	PWI_Topors	Domain
IPR058746	Znf_RING-type_Topors	Domain

Pfam: PF00097, PF26084

UniProt features (69 total): compositionally biased region 15, region of interest 11, modified residue 11, cross-link 10, mutagenesis site 9, sequence conflict 5, sequence variant 4, splice variant 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS56-F1	49.39	0.12

Functional residue map

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

Post-translational modifications (21): 98, 194, 499, 585, 718, 734, 864, 866, 912, 914, 1028, 73, 76, 83, 88, 159, 249, 560, 701, 819 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
76	no effect on sumoylation.
98	loss of phosphorylation but no effect on e3 ubiquitin-protein ligase activity.
98	increase in e3 ubiquitin-protein ligase activity and increased binding to ube2d1. no effect on sumo1-protein ligase acti
131	abrogates e3 ubiquitin-protein ligase activity.
301	no effect on sumoylation.
485	no effect on sumoylation.
560	strongly reduces sumoylation.
718	loss of phosphorylation by plk1 and increases in p53/tp53 stability.
921	no effect on sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4755510	SUMOylation of immune response proteins

MSigDB gene sets: 383 (showing top): GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, TGCACTT_MIR519C_MIR519B_MIR519A, AAGCCAT_MIR135A_MIR135B, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_MAINTENANCE_OF_LOCATION, BLALOCK_ALZHEIMERS_DISEASE_UP, USF_01

GO Biological Process (17): protein polyubiquitination (GO:0000209), DNA-templated transcription (GO:0006351), ubiquitin-dependent protein catabolic process (GO:0006511), protein monoubiquitination (GO:0006513), DNA damage response (GO:0006974), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), retina layer formation (GO:0010842), protein sumoylation (GO:0016925), protein localization to nucleus (GO:0034504), photoreceptor cell outer segment organization (GO:0035845), regulation of cell population proliferation (GO:0042127), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of DNA-templated transcription (GO:0045893), maintenance of protein location in nucleus (GO:0051457), protein K48-linked ubiquitination (GO:0070936)

GO Molecular Function (10): DNA binding (GO:0003677), antigen binding (GO:0003823), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), SUMO transferase activity (GO:0019789), DNA topoisomerase binding (GO:0044547), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (11): ubiquitin ligase complex (GO:0000151), spindle pole (GO:0000922), gamma-tubulin complex (GO:0000930), nucleus (GO:0005634), nucleoplasm (GO:0005654), centriole (GO:0005814), PML body (GO:0016605), nuclear speck (GO:0016607), midbody (GO:0030496), photoreceptor connecting cilium (GO:0032391), ciliary basal body (GO:0036064)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
cellular anatomical structure	3
microtubule organizing center	3
binding	2
ubiquitin-like protein transferase activity	2
gene expression	1
RNA biosynthetic process	1
modification-dependent protein catabolic process	1
cellular response to stress	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
neural retina development	1
anatomical structure formation involved in morphogenesis	1
retina morphogenesis in camera-type eye	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
protein localization to organelle	1
cellular component organization	1
photoreceptor cell development	1
cell population proliferation	1
regulation of cellular process	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
protein polyubiquitination	1
nucleic acid binding	1
transition metal ion binding	1
enzyme binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1

Protein interactions and networks

STRING

1316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOPORS	TOP1	P11387	820
TOPORS	KLHL7	Q8IXQ5	810
TOPORS	PRPF31	Q8WWY3	800
TOPORS	PRPF3	O43395	796
TOPORS	RP9	Q8TA86	792
TOPORS	PRPF8	Q6P2Q9	790
TOPORS	TP53	P04637	788
TOPORS	FSCN2	O14926	780
TOPORS	IMPDH1	P20839	777
TOPORS	SNRNP200	O75643	742
TOPORS	PCARE	A6NGG8	740
TOPORS	CERKL	Q49MI3	739
TOPORS	PRPH2	P23942	716
TOPORS	NR2E3	Q9Y5X4	716
TOPORS	RPGR	Q92834	709

IntAct

77 interactions, top by confidence:

A	B	Type	Score
GPANK1	TTC19	psi-mi:“MI:0914”(association)	0.740
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
SPIN1	SPINDOC	psi-mi:“MI:0914”(association)	0.640
TOPORS	UBE2D1	psi-mi:“MI:0915”(physical association)	0.550
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
ZNF816	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF214	LRP4	psi-mi:“MI:0914”(association)	0.530
SPIN2B	WDHD1	psi-mi:“MI:0914”(association)	0.530
SPIN1	PAX3	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
ZNF786	NKTR	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
TOPORS	TP53	psi-mi:“MI:0915”(physical association)	0.400
TOPORS	CASP8	psi-mi:“MI:0915”(physical association)	0.400
TOPORS	Rep78	psi-mi:“MI:0915”(physical association)	0.400
SETX	TOPORS	psi-mi:“MI:0915”(physical association)	0.370
TOPORS	SETX	psi-mi:“MI:0915”(physical association)	0.370
UBE2D2	TOPORS	psi-mi:“MI:0915”(physical association)	0.370
TOPORS	UBE2D3	psi-mi:“MI:0915”(physical association)	0.370
TOPORS	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
TOPORS	UBE2J1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (159): PLK1 (Affinity Capture-Western), UBC (Biochemical Activity), TP53 (Biochemical Activity), UBE2I (Reconstituted Complex), TOPORS (Affinity Capture-MS), TOPORS (Affinity Capture-MS), TOPORS (Affinity Capture-MS), TOPORS (Affinity Capture-MS), TOPORS (Two-hybrid), PSMC1 (Two-hybrid), PSMC1 (Affinity Capture-Western), TOPORS (Affinity Capture-MS), TOPORS (Affinity Capture-MS), TOPORS (Affinity Capture-MS), TOPORS (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z5, A2AJT4, A6NNA2, A7MD48, F1LR10, O88573, P0CB65, P51825, P51826, P51827, Q14241, Q2KJH5, Q2T9Y0, Q569Z6, Q5BJ39, Q5M7V8, Q5PPJ2, Q5RD75, Q5T6C5, Q5VUA4, Q63187, Q6QZN6, Q6ZPR1, Q80WV7, Q80Z37, Q8BKA3, Q8BM65, Q8BTI8, Q8BZX4, Q8CB77, Q8K019, Q8TF01, Q93075, Q96B23, Q96IZ7, Q96RL1, Q99PP2, Q9BW71, Q9DBU6, Q9ERQ3

Diamond homologs: A0A1L8FG46, A0A1L8FM16, B1AUE5, E7FDW2, O35445, O60683, O64425, O76064, P09309, P68907, P87176, Q09463, Q2HJ46, Q4KLN8, Q54S31, Q568Y3, Q5M807, Q5R4I2, Q5RFK9, Q5ZIR9, Q69ZS0, Q6PC78, Q803C1, Q80Z37, Q8HXW8, Q8VC56, Q91YT2, Q96GF1, Q99942, Q9NS56, Q9P3U8, Q9SYU4, Q9UPQ7, Q9UUF0, Q9V8P9, P90990, Q5M7Z0, Q6NTV1, Q6NZ21, Q8BFW4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PLK1	“up-regulates activity”	TOPORS	phosphorylation
TOPORS	down-regulates	TP53	ubiquitination
Ub:E2	“up-regulates activity”	TOPORS	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
mRNA Splicing	8	15.7×	6e-06
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	8	15.2×	6e-06
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	7	14.7×	3e-05
CLEC7A (Dectin-1) signaling	5	12.8×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	8	11.7×	3e-05
mRNA Splicing - Major Pathway	11	10.7×	2e-06
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	6	10.5×	7e-04
Regulation of expression of SLITs and ROBOs	8	9.9×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein K11-linked ubiquitination	5	26.8×	3e-04
protein monoubiquitination	5	23.6×	3e-04
protein K48-linked ubiquitination	6	13.8×	5e-04
protein polyubiquitination	8	12.7×	1e-04
mRNA splicing, via spliceosome	6	7.5×	8e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	8	5.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	11
Uncertain significance	460
Likely benign	147
Benign	16

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1071191	NM_005802.5(TOPORS):c.1882C>T (p.Arg628Ter)	Pathogenic
1656	NM_005802.5(TOPORS):c.2474dup (p.Tyr825Ter)	Pathogenic
1710123	NM_005802.5(TOPORS):c.2539del (p.Arg847fs)	Pathogenic
438066	NM_005802.5(TOPORS):c.2556_2557del (p.Glu852fs)	Pathogenic
438067	NM_005802.5(TOPORS):c.2569del (p.Arg857fs)	Pathogenic
861205	NM_005802.5(TOPORS):c.2422G>T (p.Glu808Ter)	Pathogenic
1021098	NM_005802.5(TOPORS):c.2455A>T (p.Lys819Ter)	Likely pathogenic
1066459	NM_005802.5(TOPORS):c.2084_2087del (p.Asn695fs)	Likely pathogenic
2104585	NM_005802.5(TOPORS):c.2565_2566del (p.His855fs)	Likely pathogenic
2132618	NM_005802.5(TOPORS):c.2482del (p.Ser828fs)	Likely pathogenic
2972629	NM_005802.5(TOPORS):c.2431C>T (p.Gln811Ter)	Likely pathogenic
3780729	NM_005802.5(TOPORS):c.121del (p.Arg41fs)	Likely pathogenic
802477	NM_005802.5(TOPORS):c.2895dup (p.Cys966fs)	Likely pathogenic
812433	NM_005802.5(TOPORS):c.2524dup (p.Thr842fs)	Likely pathogenic
856353	NM_005802.5(TOPORS):c.2569_2570del (p.Arg857fs)	Likely pathogenic
865844	NM_005802.5(TOPORS):c.2587dup (p.Arg863fs)	Likely pathogenic
937606	NM_005802.5(TOPORS):c.2539_2540del (p.Arg847fs)	Likely pathogenic

SpliceAI

518 predictions. Top by Δscore:

Variant	Effect	Δscore
9:32544323:TTAT:T	acceptor_gain	1.0000
9:32544323:TTATC:T	acceptor_loss	1.0000
9:32544325:ATCT:A	acceptor_loss	1.0000
9:32544326:TCTG:T	acceptor_loss	1.0000
9:32544327:C:CA	acceptor_loss	1.0000
9:32544327:C:CC	acceptor_gain	1.0000
9:32544328:T:A	acceptor_loss	1.0000
9:32552428:CCTTA:C	donor_loss	1.0000
9:32552429:CTTA:C	donor_loss	1.0000
9:32552431:TA:T	donor_loss	1.0000
9:32552432:A:AG	donor_loss	1.0000
9:32544222:A:AC	donor_gain	0.9900
9:32544322:ATTAT:A	acceptor_gain	0.9900
9:32544324:TAT:T	acceptor_gain	0.9900
9:32544325:AT:A	acceptor_gain	0.9900
9:32550772:A:AC	donor_gain	0.9900
9:32550772:A:C	donor_loss	0.9900
9:32550773:C:CC	donor_gain	0.9900
9:32550773:CCT:C	donor_gain	0.9900
9:32552432:A:AC	donor_gain	0.9900
9:32552433:C:CC	donor_gain	0.9900
9:32544222:AGAAT:A	donor_gain	0.9800
9:32544223:G:C	donor_gain	0.9800
9:32550966:CCC:C	acceptor_gain	0.9800
9:32550967:CC:C	acceptor_gain	0.9800
9:32550967:CCC:C	acceptor_gain	0.9800
9:32550968:CC:C	acceptor_gain	0.9800
9:32552427:T:TA	donor_gain	0.9800
9:32544329:G:C	acceptor_gain	0.9700
9:32552432:AC:A	donor_gain	0.9700

AlphaMissense

6856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:32543449:G:T	A359D	1.000
9:32543451:A:C	F358L	1.000
9:32543451:A:T	F358L	1.000
9:32543452:A:G	F358S	1.000
9:32543453:A:G	F358L	1.000
9:32543461:A:G	F355S	1.000
9:32543464:T:A	E354V	1.000
9:32543472:A:C	F351L	1.000
9:32543472:A:T	F351L	1.000
9:32543473:A:G	F351S	1.000
9:32543474:A:G	F351L	1.000
9:32543494:A:G	L344S	1.000
9:32543496:A:C	F343L	1.000
9:32543496:A:T	F343L	1.000
9:32543498:A:G	F343L	1.000
9:32543548:A:T	V326D	1.000
9:32543560:A:T	I322N	1.000
9:32543572:A:T	V318D	1.000
9:32543608:A:T	V306D	1.000
9:32543614:A:G	L304P	1.000
9:32543614:A:T	L304H	1.000
9:32543617:T:A	E303V	1.000
9:32543617:T:G	E303A	1.000
9:32543618:C:T	E303K	1.000
9:32543620:C:G	R302P	1.000
9:32543621:G:T	R302S	1.000
9:32543628:C:A	W299C	1.000
9:32543628:C:G	W299C	1.000
9:32543630:A:G	W299R	1.000
9:32543630:A:T	W299R	1.000

dbSNP variants (sampled 300 via entrez): RS1000187124 (9:32549228 A>C,T), RS1000202003 (9:32550471 G>A), RS1000730629 (9:32554431 G>A), RS1000731054 (9:32541698 A>G), RS1000958205 (9:32551812 C>A,T), RS1001047201 (9:32545481 G>C), RS1001262137 (9:32549319 T>C,G), RS1001414456 (9:32545576 C>G,T), RS1001610410 (9:32549052 G>A), RS1001829534 (9:32545305 C>G), RS1001860382 (9:32550520 A>G), RS1002459052 (9:32552599 C>A,G), RS1002765869 (9:32540187 C>A), RS1003096963 (9:32552781 C>T), RS1003112429 (9:32546807 T>C)

Disease associations

OMIM: gene MIM:609507 | disease phenotypes: MIM:609923, MIM:268000, MIM:167320, MIM:613954, MIM:303100

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 31	Definitive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant
ciliopathy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
TOPORS-related retinopathy	Definitive	AD

Mondo (12): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 31 (MONDO:0012367), retinitis pigmentosa (MONDO:0019200), prostate cancer (MONDO:0008315), optic atrophy (MONDO:0003608), inclusion body myopathy with Paget disease of bone and frontotemporal dementia (MONDO:0000507), frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (MONDO:0013501), choroideremia (MONDO:0010557), TOPORS-related retinopathy (MONDO:0700233), macular degeneration (MONDO:0003004), hyperopia (MONDO:0004891), ciliopathy (MONDO:0005308)

Orphanet (7): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Familial prostate cancer (Orphanet:1331), Frontotemporal dementia with motor neuron disease (Orphanet:275872), Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Orphanet:52430), Amyotrophic lateral sclerosis (Orphanet:803), Choroideremia (Orphanet:180)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000104	Renal agenesis
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000199	Tongue nodules
HP:0000218	High palate
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000565	Esotropia
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001532_2	Immune response to smallpox vaccine (IL-6)	1.000000e-07
GCST008178_4	Early spontaneous preterm birth	9.000000e-06
GCST009391_165	Metabolite levels	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0006917	spontaneous preterm birth
EFO:0010487	glutamate measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D015794	Choroideremia	C11.270.142; C11.941.160.300; C16.320.290.142; C16.320.322.092
D006956	Hyperopia	C11.744.479
D008268	Macular Degeneration	C11.768.585.439
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C563685	Retinitis Pigmentosa 31 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
K 7174	increases expression	1
jinfukang	decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2MF	HAP1 TOPORS (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa