Retinitis pigmentosa 31

Summary

Retinitis pigmentosa 31 (MONDO:0012367) is a disease caused by TOPORS (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TOPORS (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 31
Mondo ID	MONDO:0012367
MeSH	C563685
OMIM	609923
DOID	DOID:0110391
UMLS	C1835923
MedGen	372159
GARD	0010396
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 31 · retinitis pigmentosa caused by mutation in TOPORS · retinitis pigmentosa type 31 · RP 31 · RP31 · TOPORS retinitis pigmentosa

Data availability: 29 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 31

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

29 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 4 benign/likely benign, 4 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 3 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
143130	NM_005802.5(TOPORS):c.2554_2557del (p.Glu852fs)	TOPORS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1656	NM_005802.5(TOPORS):c.2474dup (p.Tyr825Ter)	TOPORS	Pathogenic	criteria provided, multiple submitters, no conflicts
1710123	NM_005802.5(TOPORS):c.2539del (p.Arg847fs)	TOPORS	Pathogenic	no assertion criteria provided
224754	NM_005802.5(TOPORS):c.2539C>T (p.Arg847Ter)	TOPORS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438066	NM_005802.5(TOPORS):c.2556_2557del (p.Glu852fs)	TOPORS	Pathogenic	criteria provided, multiple submitters, no conflicts
560511	NM_005802.5(TOPORS):c.2550_2553del (p.Asp850fs)	TOPORS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
196425	NM_005802.5(TOPORS):c.2018G>T (p.Arg673Leu)	TOPORS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3616006	NM_005802.5(TOPORS):c.59dup (p.Pro21fs)	TOPORS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
712381	NM_005802.5(TOPORS):c.2484_2486del (p.Ser830del)	TOPORS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
940703	NM_005802.5(TOPORS):c.3126_3127del (p.Cys1042_Asp1043delinsTer)	TOPORS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1065723	NM_005802.5(TOPORS):c.2038AGA[1] (p.Arg681del)	TOPORS	Uncertain significance	criteria provided, multiple submitters, no conflicts
1806057	NM_005802.5(TOPORS):c.2866G>C (p.Glu956Gln)	TOPORS	Uncertain significance	criteria provided, single submitter
1920258	NM_005802.5(TOPORS):c.2791C>T (p.Pro931Ser)	TOPORS	Uncertain significance	criteria provided, multiple submitters, no conflicts
289956	NM_005802.5(TOPORS):c.1795A>C (p.Ser599Arg)	TOPORS	Uncertain significance	criteria provided, multiple submitters, no conflicts
3597250	NM_005802.5(TOPORS):c.2674A>C (p.Lys892Gln)	TOPORS	Uncertain significance	criteria provided, single submitter
3892696	NM_005802.5(TOPORS):c.2594T>C (p.Leu865Pro)	TOPORS	Uncertain significance	criteria provided, single submitter
489321	NM_005802.5(TOPORS):c.2995A>T (p.Arg999Ter)	TOPORS	Uncertain significance	criteria provided, single submitter
523486	NM_005802.5(TOPORS):c.1379G>C (p.Gly460Ala)	TOPORS	Uncertain significance	criteria provided, single submitter
523487	NM_005802.5(TOPORS):c.2666A>G (p.His889Arg)	TOPORS	Uncertain significance	criteria provided, multiple submitters, no conflicts
599169	NM_005802.5(TOPORS):c.2319_2320delinsCG (p.Ser774Gly)	TOPORS	Uncertain significance	no assertion criteria provided
618438	NM_005802.5(TOPORS):c.2006G>A (p.Arg669Lys)	TOPORS	Uncertain significance	criteria provided, single submitter
811354	NM_005802.5(TOPORS):c.842T>A (p.Ile281Asn)	TOPORS	Uncertain significance	criteria provided, single submitter
865900	NM_005802.5(TOPORS):c.2552G>A (p.Arg851Lys)	TOPORS	Uncertain significance	criteria provided, multiple submitters, no conflicts
931667	NM_005802.5(TOPORS):c.223T>C (p.Phe75Leu)	TOPORS	Uncertain significance	criteria provided, multiple submitters, no conflicts
1169839	NM_005802.5(TOPORS):c.2349G>A (p.Gly783=)	TOPORS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
195250	NM_005802.5(TOPORS):c.74C>G (p.Ser25Trp)	TOPORS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
284409	NM_005802.5(TOPORS):c.2160C>T (p.Tyr720=)	TOPORS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
366559	NM_005802.5(TOPORS):c.2988C>T (p.Leu996=)	TOPORS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
95313	NM_005802.5(TOPORS):c.2319T>C (p.Ser773=)	TOPORS	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TOPORS	Definitive	Autosomal dominant	retinitis pigmentosa 31	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TOPORS	Orphanet:2754	Orofaciodigital syndrome type 6
TOPORS	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TOPORS	HGNC:21653	ENSG00000197579	Q9NS56	E3 ubiquitin-protein ligase Topors	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TOPORS	E3 ubiquitin-protein ligase Topors	Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TOPORS	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
secondary oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TOPORS	285	ubiquitous	marker	secondary oocyte, calcaneal tendon, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TOPORS	1,552

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TOPORS	Q9NS56	49.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SUMOylation of immune response proteins	1	951.7×	0.003	TOPORS
SUMOylation of SUMOylation proteins	1	326.3×	0.004	TOPORS
SUMOylation of transcription cofactors	1	243.0×	0.004	TOPORS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of protein location in nucleus	1	1123.5×	0.007	TOPORS
photoreceptor cell outer segment organization	1	1053.2×	0.007	TOPORS
retina layer formation	1	648.1×	0.007	TOPORS
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	495.6×	0.007	TOPORS
protein localization to nucleus	1	351.1×	0.007	TOPORS
protein monoubiquitination	1	343.9×	0.007	TOPORS
intrinsic apoptotic signaling pathway in response to DNA damage	1	324.1×	0.007	TOPORS
protein sumoylation	1	324.1×	0.007	TOPORS
DNA-templated transcription	1	224.7×	0.008	TOPORS
protein K48-linked ubiquitination	1	168.5×	0.010	TOPORS
protein polyubiquitination	1	115.4×	0.012	TOPORS
regulation of cell population proliferation	1	115.4×	0.012	TOPORS
ubiquitin-dependent protein catabolic process	1	74.2×	0.018	TOPORS
DNA damage response	1	53.5×	0.022	TOPORS
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.022	TOPORS
negative regulation of apoptotic process	1	34.8×	0.031	TOPORS
positive regulation of DNA-templated transcription	1	27.9×	0.036	TOPORS

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TOPORS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TOPORS

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TOPORS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.