TOPORS

TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase, the group of Ring finger proteins

Basic information

Region (hg38): 9:32540543-32552586

Previous symbols: [ "RP31" ]

Links

ENSG00000197579 ∙ NCBI:10210 ∙ OMIM:609507 ∙ HGNC:21653 ∙ Uniprot:Q9NS56 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 31 (Strong), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 31 (Definitive), mode of inheritance: AD
• inherited retinal dystrophy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retitinis pigmentosa 31	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	16189705; 17924349; 18509552; 19183411

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TOPORS gene.

• not provided (456 variants)
• Retinitis pigmentosa (73 variants)
• Inborn genetic diseases (40 variants)
• Retinitis pigmentosa 31 (18 variants)
• not specified (12 variants)
• Retinal dystrophy (10 variants)
• Retinitis Pigmentosa, Dominant (6 variants)
• TOPORS-related condition (2 variants)
• 7 conditions (1 variants)
• Blurred vision;Macular degeneration;Pigmentary retinopathy;Abnormality of retinal pigmentation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOPORS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	112	6	126
missense			281	9	5	295
nonsense	3	1	2			6
start loss			1			1
frameshift	1	6	10			17
inframe indel			8	1		9
splice donor/acceptor (+/-2bp)			3			3
splice region			3	3		6
non coding			19	9	3	31
Total	4	7	332	131	14

Variants in TOPORS

This is a list of pathogenic ClinVar variants found in the TOPORS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-32540649-ATAAAG-A		Retinitis Pigmentosa, Dominant	Likely benign (Jun 14, 2016)
9-32540701-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
9-32540739-T-TA		Retinitis Pigmentosa, Dominant	Uncertain significance (Jun 14, 2016)
9-32540747-A-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32540881-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32540957-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541016-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541024-CA-C		Retinitis Pigmentosa, Dominant	Likely benign (Jun 14, 2016)
9-32541029-A-G		Retinitis pigmentosa	Uncertain significance (Mar 16, 2018)
9-32541037-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541046-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
9-32541078-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
9-32541079-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541087-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541247-CA-C		Retinitis Pigmentosa, Dominant	Likely benign (Jun 14, 2016)
9-32541247-C-CA		Retinitis Pigmentosa, Dominant	Uncertain significance (Jun 14, 2016)
9-32541270-T-C		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
9-32541287-G-C		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
9-32541340-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541363-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
9-32541378-T-C		Retinitis pigmentosa	Benign (Jan 12, 2018)
9-32541389-A-T			Uncertain significance (Jul 05, 2022)
9-32541397-TCA-T		Retinitis pigmentosa 31	Conflicting classifications of pathogenicity (Jun 09, 2023)
9-32541417-T-C			Likely benign (Mar 20, 2023)
9-32541432-T-A			Likely benign (May 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOPORS	protein_coding	protein_coding	ENST00000360538	3	12010

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000957	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	486	556	0.875	0.0000298	6832
Missense in Polyphen		101	154.13	0.6553		1831
Synonymous	-1.21	223	201	1.11	0.0000101	2047
Loss of Function	5.09	4	37.8	0.106	0.00000264	475

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.000220	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000714	0.0000703
Middle Eastern	0.000220	0.000217
South Asian	0.000131	0.000131
Other	0.000341	0.000326

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15735665, ECO:0000269|PubMed:16122737, ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:18077445, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:20188669}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:17924349}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.173
• rvis_EVS: 0.03
• rvis_percentile_EVS: 55.81

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.731
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.884

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Topors

Zebrafish Information Network

• Gene name: toporsa
• Affected structure: photoreceptor outer segment layer
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: protein polyubiquitination;transcription, DNA-templated;ubiquitin-dependent protein catabolic process;protein monoubiquitination;cellular response to DNA damage stimulus;intrinsic apoptotic signaling pathway in response to DNA damage;retina layer formation;protein sumoylation;protein localization to nucleus;photoreceptor cell outer segment organization;regulation of cell population proliferation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;negative regulation of apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of transcription, DNA-templated;retinal rod cell development;retinal cone cell development;positive regulation of ubiquitin-protein transferase activity;maintenance of protein location in nucleus;protein K48-linked ubiquitination
• Cellular component: ubiquitin ligase complex;spindle pole;gamma-tubulin complex;nucleus;nucleoplasm;centriole;cytoplasmic dynein complex;PML body;nuclear speck;midbody;photoreceptor connecting cilium;ciliary basal body
• Molecular function: DNA binding;antigen binding;ubiquitin-protein transferase activity;protein binding;SUMO transferase activity;DNA topoisomerase binding;metal ion binding;ubiquitin protein ligase activity