Retinitis pigmentosa 23

Summary

Retinitis pigmentosa 23 (MONDO:0010320) is a disease caused by OFD1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: OFD1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 138

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 23
Mondo ID	MONDO:0010320
OMIM	300424
DOID	DOID:0110412
UMLS	C1419610
MedGen	238456
GARD	0010391
Is cancer (heuristic)	no

Also known as: OFD1 retinitis pigmentosa · retinitis pigmentosa 23 · retinitis pigmentosa 23, X-linked recessive · retinitis pigmentosa caused by mutation in OFD1 · retinitis pigmentosa type 23 · RP 23 · RP23

Data availability: 138 ClinVar variants · 2 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 23

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 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 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

138 retrieved; paginated sample, class counts are floors:

84 uncertain significance, 19 conflicting classifications of pathogenicity, 19 benign/likely benign, 6 likely benign, 5 pathogenic, 2 benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179099	NM_003611.3(OFD1):c.1411+1G>A	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
3598083	NM_003611.3(OFD1):c.1604dup (p.Leu535fs)	OFD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41065	NM_003611.3(OFD1):c.1193_1196del (p.Gln398fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
41066	NM_003611.3(OFD1):c.121C>T (p.Arg41Ter)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
41117	NM_003611.3(OFD1):c.400_403del (p.Glu134fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
41143	NM_003611.3(OFD1):c.710dup (p.Tyr238fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
3382813	NM_003611.3(OFD1):c.1597_1598del (p.Lys533fs)	OFD1	Likely pathogenic	criteria provided, single submitter
3598070	NM_003611.3(OFD1):c.1055+1G>T	OFD1	Likely pathogenic	criteria provided, single submitter
1106239	NM_003611.3(OFD1):c.1015G>A (p.Glu339Lys)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1167595	NM_003611.3(OFD1):c.494C>T (p.Ser165Leu)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1336345	NM_003611.3(OFD1):c.2726G>A (p.Arg909Gln)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1630578	NM_003611.3(OFD1):c.3027C>G (p.Asp1009Glu)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1911357	NM_003611.3(OFD1):c.2672G>A (p.Arg891Lys)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2083669	NM_003611.3(OFD1):c.2928+7G>A	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211787	NM_003611.3(OFD1):c.2584T>G (p.Ser862Ala)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2142621	NM_003611.3(OFD1):c.2940G>C (p.Lys980Asn)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2180521	NM_003611.3(OFD1):c.2489-13G>A	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2199921	NM_003611.3(OFD1):c.2372C>T (p.Pro791Leu)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2208670	NM_003611.3(OFD1):c.2647C>T (p.Arg883Trp)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2926333	NM_003611.3(OFD1):c.2261G>A (p.Gly754Asp)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3598081	NM_003611.3(OFD1):c.1559A>G (p.Gln520Arg)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3598087	NM_003611.3(OFD1):c.1804C>T (p.Arg602Cys)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532267	NM_003611.3(OFD1):c.892G>A (p.Gly298Arg)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
571289	NM_003611.3(OFD1):c.324G>A (p.Met108Ile)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
593063	NM_003611.3(OFD1):c.730A>G (p.Met244Val)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
975456	NM_003611.3(OFD1):c.382G>A (p.Val128Ile)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
982582	NM_003611.3(OFD1):c.2176C>T (p.Arg726Cys)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1486282	NM_003611.3(OFD1):c.74A>G (p.Gln25Arg)	LOC126863212	Uncertain significance	criteria provided, multiple submitters, no conflicts
2933554	NM_003611.3(OFD1):c.111+6G>A	LOC126863212	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598057	NM_003611.3(OFD1):c.1A>G (p.Met1Val)	LOC126863212	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 5 · 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
OFD1	Strong	X-linked	retinitis pigmentosa 23	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	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
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OFD1	Other/Unknown	no		LisH, OFD1

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
bronchial epithelial cell	1
cervix squamous epithelium	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OFD1	2,878

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OFD1	O75665	68.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Hedgehog ‘off’ state	1	178.4×	0.009	OFD1
Loss of Nlp from mitotic centrosomes	1	158.6×	0.009	OFD1
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.009	OFD1
AURKA Activation by TPX2	1	152.3×	0.009	OFD1
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.009	OFD1
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.009	OFD1
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.009	OFD1
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	OFD1

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
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	8426.0×	6e-04	OFD1
embryonic body morphogenesis	1	2106.5×	0.001	OFD1
epithelial cilium movement involved in determination of left/right asymmetry	1	1296.3×	0.001	OFD1
axoneme assembly	1	543.6×	0.002	OFD1
cilium assembly	1	73.6×	0.014	OFD1

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
OFD1	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	OFD1

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)
OFD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.