Retinitis pigmentosa 54

Summary

Retinitis pigmentosa 54 (MONDO:0013263) is a disease caused by PCARE (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PCARE (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 54
Mondo ID	MONDO:0013263
OMIM	613428
DOID	DOID:0110364
UMLS	C3150691
MedGen	462041
GARD	0015662
Is cancer (heuristic)	no

Also known as: PCARE retinitis pigmentosa · retinitis pigmentosa 54 · retinitis pigmentosa caused by mutation in PCARE · retinitis pigmentosa type 54 · RP54

Data availability: 71 ClinVar variants · 1 GenCC gene-disease record.

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 54

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 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 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:

17 pathogenic, 13 benign, 12 likely pathogenic, 11 uncertain significance, 6 conflicting classifications of pathogenicity, 6 benign/likely benign, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
101	NM_001029883.3(PCARE):c.759G>A (p.Trp253Ter)	PCARE	Pathogenic	no assertion criteria provided
103	NM_001029883.3(PCARE):c.947del (p.Asn316fs)	PCARE	Pathogenic	criteria provided, single submitter
104	NM_001029883.3(PCARE):c.556C>T (p.Gln186Ter)	PCARE	Pathogenic	no assertion criteria provided
1049580	NM_001029883.3(PCARE):c.920T>A (p.Leu307Ter)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
105	NM_001029883.3(PCARE):c.2756_2768del (p.Lys919fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
1074451	NM_001029883.3(PCARE):c.1273C>T (p.Arg425Ter)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
1184960	NM_001029883.3(PCARE):c.2966dup (p.Val990fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
1456390	NM_001029883.3(PCARE):c.3346_3349del (p.Ser1116fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
2823321	NM_001029883.3(PCARE):c.2159G>A (p.Trp720Ter)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
3028814	NM_001029883.3(PCARE):c.3358_3359del (p.His1120fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
4292812	NM_001029883.3(PCARE):c.770_774del (p.Lys257fs)	PCARE	Pathogenic	criteria provided, single submitter
438048	NM_001029883.3(PCARE):c.3002G>A (p.Trp1001Ter)	PCARE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522284	NM_001029883.3(PCARE):c.1545dup (p.Ser516fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
599266	NM_001029883.3(PCARE):c.1191G>A (p.Trp397Ter)	PCARE	Pathogenic	criteria provided, single submitter
808719	NM_001029883.3(PCARE):c.2380dup (p.Met794fs)	PCARE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812237	NM_001029883.3(PCARE):c.3289C>T (p.Gln1097Ter)	PCARE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
839525	NM_001029883.3(PCARE):c.3604C>T (p.Arg1202Ter)	PCARE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
841159	NM_001029883.3(PCARE):c.1837C>T (p.Arg613Ter)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
866068	NM_001029883.3(PCARE):c.958del (p.Arg320fs)	PCARE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871084	NM_001029883.3(PCARE):c.1541del (p.Pro514fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
973351	NM_001029883.3(PCARE):c.1229del (p.Gln410fs)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
979001	NM_001029883.3(PCARE):c.2967del (p.Val990fs)	PCARE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
987347	NM_001029883.3(PCARE):c.2704A>T (p.Lys902Ter)	PCARE	Pathogenic	criteria provided, multiple submitters, no conflicts
1065729	NM_001029883.3(PCARE):c.1612C>T (p.Gln538Ter)	PCARE	Likely pathogenic	criteria provided, single submitter
1065770	NM_001029883.3(PCARE):c.1894A>T (p.Lys632Ter)	PCARE	Likely pathogenic	criteria provided, single submitter
1065771	NM_001029883.3(PCARE):c.1663del (p.Val555fs)	PCARE	Likely pathogenic	criteria provided, single submitter
1213961	NM_001029883.3(PCARE):c.2424del (p.Pro809fs)	PCARE	Likely pathogenic	criteria provided, single submitter
1213962	NM_001029883.3(PCARE):c.2415del (p.Pro807fs)	PCARE	Likely pathogenic	criteria provided, single submitter
2444372	NM_001029883.3(PCARE):c.3048_3049del (p.Tyr1016_Arg1017delinsTer)	PCARE	Likely pathogenic	criteria provided, single submitter
2628065	NM_001029883.3(PCARE):c.938_946dup (p.Arg315_Asn316insThrLysArg)	PCARE	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
PCARE	Definitive	Autosomal recessive	retinitis pigmentosa 54	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PCARE	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
PCARE	HGNC:34383	ENSG00000179270	A6NGG8	Photoreceptor cilium actin regulator	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PCARE	Photoreceptor cilium actin regulator	Plays an essential role for normal photoreceptor cell maintenance and vision.

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)
PCARE	Other/Unknown	no		PCARE

Expression context

Cohort genes with no expression data: 0.

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
apex of heart	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PCARE	78	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, apex of heart, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCARE	481

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PCARE	A6NGG8	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
protein localization to photoreceptor outer segment	1	2407.4×	0.001	PCARE
photoreceptor cell outer segment organization	1	1053.2×	0.001	PCARE
visual perception	1	79.5×	0.013	PCARE

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
PCARE	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	PCARE

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)
PCARE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.