Retinitis pigmentosa 14

Summary

Retinitis pigmentosa 14 (MONDO:0010827) is a disease caused by TULP1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: TULP1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 14
Mondo ID	MONDO:0010827
OMIM	600132
DOID	DOID:0110381
UMLS	C1838603
MedGen	325056
GARD	0010385
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 14 · retinitis pigmentosa caused by mutation in TULP1 · retinitis pigmentosa type 14 · RP 14 · RP14 · TULP1 retinitis pigmentosa

Data availability: 71 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 14

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 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 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

71 retrieved; paginated sample, class counts are floors:

18 pathogenic, 17 pathogenic/likely pathogenic, 12 uncertain significance, 10 likely pathogenic, 9 conflicting classifications of pathogenicity, 5 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
7358	NM_003322.6(TULP1):c.1471T>C (p.Phe491Leu)	TEAD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028595	NM_003322.6(TULP1):c.1255del (p.Arg419fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065758	NM_003322.6(TULP1):c.932G>A (p.Arg311Gln)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065768	NM_003322.6(TULP1):c.187G>T (p.Gly63Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1069193	NM_003322.6(TULP1):c.1255C>T (p.Arg419Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184552	NM_003322.6(TULP1):c.1066C>A (p.Pro356Thr)	TULP1	Pathogenic	no assertion criteria provided
1184553	NC_000006.12:g.35506278_35506281del	TULP1	Pathogenic	no assertion criteria provided
1708378	NM_003322.6(TULP1):c.162dup (p.Thr55fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136379	NM_003322.6(TULP1):c.1081C>T (p.Arg361Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
2734854	NM_003322.6(TULP1):c.627del (p.Ser210fs)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
30262	NM_003322.6(TULP1):c.1102G>T (p.Gly368Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382016	NM_003322.6(TULP1):c.310del (p.Glu104fs)	TULP1	Pathogenic	criteria provided, single submitter
3906949	NM_003322.6(TULP1):c.453dup (p.Ser152fs)	TULP1	Pathogenic	criteria provided, single submitter
444681	NM_003322.6(TULP1):c.1268T>C (p.Val423Ala)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7357	NM_003322.6(TULP1):c.1259G>C (p.Arg420Pro)	TULP1	Pathogenic	criteria provided, single submitter
7362	NM_003322.6(TULP1):c.1145T>C (p.Phe382Ser)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
7364	NM_003322.6(TULP1):c.1511_1521del (p.Leu504fs)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
7365	NM_003322.6(TULP1):c.718+2T>C	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
802208	NM_003322.6(TULP1):c.1388del (p.Asn463fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802210	NM_003322.6(TULP1):c.931C>T (p.Arg311Trp)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812440	NM_003322.6(TULP1):c.1047T>G (p.Asn349Lys)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813100	NM_003322.6(TULP1):c.1201C>T (p.Gln401Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
828151	NM_003322.6(TULP1):c.901C>T (p.Gln301Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
852847	NM_003322.6(TULP1):c.1199G>A (p.Arg400Gln)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
865921	NM_003322.6(TULP1):c.821del (p.Lys274fs)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866967	NM_003322.6(TULP1):c.1318C>T (p.Arg440Ter)	TULP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
872549	NM_003322.6(TULP1):c.629C>G (p.Ser210Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
971453	NM_003322.6(TULP1):c.238C>T (p.Gln80Ter)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
977975	NM_003322.6(TULP1):c.148del (p.Glu50fs)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts
977980	NM_003322.6(TULP1):c.1445G>A (p.Arg482Gln)	TULP1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
TULP1	Definitive	Autosomal recessive	retinitis pigmentosa 14	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TULP1	Orphanet:65	Leber congenital amaurosis
TULP1	Orphanet:791	Retinitis pigmentosa
PRPF8	Orphanet:528084	Non-specific syndromic intellectual disability
PRPF8	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TULP1	HGNC:12423	ENSG00000112041	O00294	Tubby-related protein 1	gencc,clinvar
TEAD3	HGNC:11716	ENSG00000007866	Q99594	Transcriptional enhancer factor TEF-5	clinvar
PRPF8	HGNC:17340	ENSG00000174231	Q6P2Q9	Pre-mRNA-processing-splicing factor 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TULP1	Tubby-related protein 1	Required for normal development of photoreceptor synapses.
TEAD3	Transcriptional enhancer factor TEF-5	Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
PRPF8	Pre-mRNA-processing-splicing factor 8	Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TULP1	Other/Unknown	no		Tubby_C, Tubby_C_CS, Tubby-like_C
TEAD3	Other/Unknown	no		TEA/ATTS_dom, TEF_metazoa, TEF-5
PRPF8	Other/Unknown	no		JAMM/MPN+_dom, RNaseH-like_sf, PRO8NT

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	1
retina	1
tendon of biceps brachii	1
lower esophagus	1
lower esophagus muscularis layer	1
muscle layer of sigmoid colon	1
adenohypophysis	1
pituitary gland	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TULP1	134	tissue_specific	marker	primordial germ cell in gonad, tendon of biceps brachii, retina
TEAD3	247	ubiquitous	marker	muscle layer of sigmoid colon, lower esophagus, lower esophagus muscularis layer
PRPF8	145	ubiquitous	marker	adenohypophysis, pituitary gland, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRPF8	5,582
TEAD3	1,560
TULP1	760

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRPF8	Q6P2Q9	101
TEAD3	Q99594	10
TULP1	O00294	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates YAP1-mediated transcription	1	713.8×	0.013	TEAD3
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	380.7×	0.013	TEAD3
Transcriptional regulation by RUNX3	1	135.9×	0.022	TEAD3
mRNA Splicing - Minor Pathway	1	112.0×	0.022	PRPF8
Regulation of PD-L1(CD274) transcription	1	54.4×	0.037	TEAD3
mRNA Splicing - Major Pathway	1	27.3×	0.060	PRPF8
Dengue Virus-Host Interactions	1	22.8×	0.062	PRPF8
RNA Polymerase II Transcription	1	11.3×	0.109	TEAD3
Gene expression (Transcription)	1	8.9×	0.121	TEAD3
Generic Transcription Pathway	1	7.5×	0.128	TEAD3

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
asymmetric neuroblast division	1	1872.4×	0.011	TEAD3
protein localization to photoreceptor outer segment	1	802.5×	0.011	TULP1
phagocytosis, recognition	1	702.2×	0.011	TULP1
spliceosomal tri-snRNP complex assembly	1	374.5×	0.013	PRPF8
retina homeostasis	1	374.5×	0.013	TULP1
eye photoreceptor cell development	1	280.9×	0.013	TULP1
hippo signaling	1	244.2×	0.013	TEAD3
detection of light stimulus involved in visual perception	1	216.1×	0.013	TULP1
RNA splicing, via transesterification reactions	1	208.1×	0.013	PRPF8
embryonic organ development	1	160.5×	0.015	TEAD3
protein localization to cilium	1	133.8×	0.015	TULP1
dendrite development	1	130.6×	0.015	TULP1
photoreceptor cell maintenance	1	119.5×	0.015	TULP1
positive regulation of phagocytosis	1	106.0×	0.016	TULP1
retina development in camera-type eye	1	85.1×	0.019	TULP1
female pregnancy	1	70.2×	0.021	TEAD3
cellular response to tumor necrosis factor	1	54.5×	0.026	PRPF8
cellular response to lipopolysaccharide	1	32.7×	0.040	PRPF8
mRNA splicing, via spliceosome	1	30.5×	0.040	PRPF8
RNA splicing	1	29.4×	0.040	PRPF8
visual perception	1	26.5×	0.041	TULP1
mRNA processing	1	26.2×	0.041	PRPF8
positive regulation of transcription by RNA polymerase II	1	5.0×	0.197	TEAD3
regulation of transcription by RNA polymerase II	1	3.9×	0.236	TEAD3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TEAD3	1	2
PRPF8	1	2
TULP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PIRLINDOLE	2	TEAD3
MOLIBRESIB	2	PRPF8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TEAD3	39	Binding:39
PRPF8	8	Binding:8

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

2 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)
PIRLINDOLE	2	TEAD3
MOLIBRESIB	2	PRPF8

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	2	TEAD3, PRPF8
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TULP1

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)
TULP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.