Retinitis pigmentosa 11

Summary

Retinitis pigmentosa 11 (MONDO:0010828) is a disease caused by PRPF31 (GenCC Definitive), with 4 cohort genes and 4 clinical trials.

At a glance

• Causal gene: PRPF31 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 94
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 11
Mondo ID	MONDO:0010828
MeSH	C563991
OMIM	600138
DOID	DOID:0110408
UMLS	C1838601
MedGen	325055
GARD	0010383
Is cancer (heuristic)	no

Also known as: PRPF31 retinitis pigmentosa · retinitis pigmentosa 11 · retinitis pigmentosa caused by mutation in PRPF31 · retinitis pigmentosa type 11 · RP 11 · RP11

Data availability: 94 ClinVar variants · 4 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 11

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 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 31, 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

94 retrieved; paginated sample, class counts are floors:

27 likely pathogenic, 26 pathogenic, 16 uncertain significance, 13 pathogenic/likely pathogenic, 7 conflicting classifications of pathogenicity, 4 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2579241	GRCh38/hg38 19q13.42(chr19:54106667-54131817)x1	NDUFA3	Pathogenic	criteria provided, single submitter
2579242	GRCh38/hg38 19q13.42(chr19:54105500-54126715)x1	NDUFA3	Pathogenic	criteria provided, single submitter
1065676	NM_015629.4(PRPF31):c.523C>T (p.Gln175Ter)	PRPF31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172723	NM_015629.4(PRPF31):c.176del (p.Met59fs)	PRPF31	Pathogenic	criteria provided, single submitter
1297104	NM_015629.4(PRPF31):c.1165C>T (p.Gln389Ter)	PRPF31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1355432	NM_015629.4(PRPF31):c.866_879del (p.Arg289fs)	PRPF31	Pathogenic	criteria provided, multiple submitters, no conflicts
1456317	NM_015629.4(PRPF31):c.528-39_531del	PRPF31	Pathogenic	criteria provided, multiple submitters, no conflicts
1686099	NM_015629.4(PRPF31):c.205del (p.Glu69fs)	PRPF31	Pathogenic	criteria provided, single submitter
2152321	NM_015629.4(PRPF31):c.238+1G>A	PRPF31	Pathogenic	criteria provided, multiple submitters, no conflicts
224758	NM_015629.4(PRPF31):c.1120C>T (p.Gln374Ter)	PRPF31	Pathogenic	criteria provided, multiple submitters, no conflicts
2579238	GRCh38/hg38 19q13.42(chr19:54121739-54129468)x1	PRPF31	Pathogenic	criteria provided, single submitter
2579239	GRCh38/hg38 19q13.42(chr19:54121739-54131817)x1	PRPF31	Pathogenic	criteria provided, single submitter
2579240	GRCh38/hg38 19q13.42(chr19:54114345-54129468)x1	PRPF31	Pathogenic	criteria provided, single submitter
3235232	NM_015629.4(PRPF31):c.1A>G (p.Met1Val)	PRPF31	Pathogenic	criteria provided, single submitter
3236217	NM_015629.4(PRPF31):c.845_855+1del	PRPF31	Pathogenic	criteria provided, single submitter
3382366	NM_015629.4(PRPF31):c.420+1G>A	PRPF31	Pathogenic	criteria provided, single submitter
4358	NM_015629.4(PRPF31):c.1115_1125del (p.Arg372fs)	PRPF31	Pathogenic	no assertion criteria provided
4359	NM_015629.4(PRPF31):c.646G>C (p.Ala216Pro)	PRPF31	Pathogenic	no assertion criteria provided
4360	NM_015629.4(PRPF31):c.527+3A>G	PRPF31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4362	NM_015629.4(PRPF31):c.581C>A (p.Ala194Glu)	PRPF31	Pathogenic	no assertion criteria provided
4364	NM_015629.4(PRPF31):c.770dup (p.Thr258fs)	PRPF31	Pathogenic	no assertion criteria provided
4365	NM_015629.4(PRPF31):c.332_343del (p.His111_Ile114del)	PRPF31	Pathogenic	criteria provided, single submitter
4366	NM_015629.4(PRPF31):c.1374+654C>G	PRPF31	Pathogenic	criteria provided, single submitter
444485	NM_015629.4(PRPF31):c.904del (p.Ala302Glnfs)	PRPF31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
500129	NM_015629.4(PRPF31):c.973G>T (p.Glu325Ter)	PRPF31	Pathogenic	criteria provided, multiple submitters, no conflicts
546035	NM_015629.4(PRPF31):c.992G>A (p.Trp331Ter)	PRPF31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560487	NM_015629.4(PRPF31):c.1291C>T (p.Gln431Ter)	PRPF31	Pathogenic	criteria provided, single submitter
599085	GRCh37/hg19 19q13.42(chr19:54618744-54622073)x1	PRPF31	Pathogenic	no assertion criteria provided
636070	NM_015629.4(PRPF31):c.855+1G>T	PRPF31	Pathogenic	criteria provided, single submitter
865976	NM_015629.4(PRPF31):c.895T>C (p.Cys299Arg)	PRPF31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
PRPF31	Definitive	Autosomal dominant	retinitis pigmentosa 11	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRPF31	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRPF31	HGNC:15446	ENSG00000105618	Q8WWY3	U4/U6 small nuclear ribonucleoprotein Prp31	gencc,clinvar
TFPT	HGNC:13630	ENSG00000105619	P0C1Z6	TCF3 fusion partner	clinvar
PRPF31-AS1	HGNC:40700	ENSG00000237017		PRPF31 antisense RNA 1	clinvar
NDUFA3	HGNC:7686	ENSG00000170906	O95167	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRPF31	U4/U6 small nuclear ribonucleoprotein Prp31	Involved in pre-mRNA splicing as component of the spliceosome.
TFPT	TCF3 fusion partner	Appears to promote apoptosis in a p53/TP53-independent manner.
NDUFA3	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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
Other/Unknown	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRPF31	Other/Unknown	no		Nop_dom, NOSIC, Prp31_C
TFPT	Other/Unknown	no		TFPT, INO80F
PRPF31-AS1	Other/Unknown	no
NDUFA3	Other/Unknown	no		NDUFA3

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
stromal cell of endometrium	1
ventricular zone	1
amygdala	1
prefrontal cortex	1
temporal lobe	1
right adrenal gland	1
right adrenal gland cortex	1
sural nerve	1
hindlimb stylopod muscle	1
primary visual cortex	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRPF31	134	ubiquitous	marker	stromal cell of endometrium, granulocyte, ventricular zone
TFPT	134	ubiquitous	marker	amygdala, temporal lobe, prefrontal cortex
PRPF31-AS1	126		yes	right adrenal gland cortex, right adrenal gland, sural nerve
NDUFA3	134	ubiquitous	marker	primary visual cortex, hindlimb stylopod muscle, superior frontal gyrus

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRPF31	3,427
NDUFA3	1,893
TFPT	1,639
PRPF31-AS1	0

Intra-cohort edges

A	B	Sources
NDUFA3	TFPT	string_interaction
PRPF31	TFPT	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRPF31	Q8WWY3	30
NDUFA3	O95167	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TFPT	P0C1Z6	67.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Global Genome Nucleotide Excision Repair (GG-NER)	1	152.3×	0.045	TFPT
DNA Damage Recognition in GG-NER	1	95.2×	0.045	TFPT
Nucleotide Excision Repair	1	95.2×	0.045	TFPT
Complex I biogenesis	1	55.2×	0.048	NDUFA3
Deubiquitination	1	41.4×	0.048	TFPT
UCH proteinases	1	41.4×	0.048	TFPT
DNA Repair	1	32.8×	0.048	TFPT
Respiratory electron transport	1	31.7×	0.048	NDUFA3
Aerobic respiration and respiratory electron transport	1	29.5×	0.048	NDUFA3
mRNA Splicing - Major Pathway	1	18.2×	0.070	PRPF31
Post-translational protein modification	1	6.4×	0.175	TFPT
Metabolism of proteins	1	4.1×	0.237	TFPT
Metabolism	1	3.9×	0.237	NDUFA3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ribonucleoprotein complex localization	1	5617.3×	0.004	PRPF31
spliceosomal tri-snRNP complex assembly	1	374.5×	0.013	PRPF31
positive regulation of telomere maintenance in response to DNA damage	1	374.5×	0.013	TFPT
regulation of DNA strand elongation	1	351.1×	0.013	TFPT
regulation of chromosome organization	1	312.1×	0.013	TFPT
regulation of DNA replication	1	122.1×	0.018	TFPT
mitochondrial electron transport, NADH to ubiquinone	1	119.5×	0.018	NDUFA3
positive regulation of DNA repair	1	119.5×	0.018	TFPT
DNA recombination	1	112.3×	0.018	TFPT
regulation of embryonic development	1	110.1×	0.018	TFPT
regulation of DNA repair	1	92.1×	0.018	TFPT
telomere maintenance	1	89.2×	0.018	TFPT
proton motive force-driven mitochondrial ATP synthesis	1	87.8×	0.018	NDUFA3
aerobic respiration	1	82.6×	0.018	NDUFA3
apoptotic signaling pathway	1	74.9×	0.019	TFPT
mRNA splicing, via spliceosome	1	30.5×	0.043	PRPF31
regulation of cell cycle	1	24.9×	0.047	TFPT
chromatin remodeling	1	24.3×	0.047	TFPT
DNA repair	1	21.3×	0.051	TFPT
positive regulation of apoptotic process	1	18.9×	0.055	TFPT
positive regulation of DNA-templated transcription	1	9.3×	0.104	TFPT

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRPF31	1	2
TFPT	0	0
PRPF31-AS1	0	0
NDUFA3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	PRPF31

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRPF31	6	Binding:6
NDUFA3	4	Binding:4

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	PRPF31

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	1	PRPF31
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	TFPT, PRPF31-AS1, NDUFA3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TFPT	0	PRPF31
PRPF31-AS1	0	—
NDUFA3	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
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
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04805658	Not specified	ACTIVE_NOT_RECRUITING	Natural History Study of Retinitis Pigmentosa Type 11