Retinitis pigmentosa 19

Summary

Retinitis pigmentosa 19 (MONDO:0011137) is a disease caused by ABCA4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ABCA4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 259

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 19
Mondo ID	MONDO:0011137
MeSH	C566637
OMIM	601718
DOID	DOID:0110354
UMLS	C1866422
MedGen	400996
GARD	0010398
Is cancer (heuristic)	no

Also known as: ABCA4 retinitis pigmentosa · retinitis pigmentosa 19 · retinitis pigmentosa caused by mutation in ABCA4 · retinitis pigmentosa type 19 · RP 19 · RP19

Data availability: 259 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 19

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 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

259 retrieved; paginated sample, class counts are floors:

83 pathogenic/likely pathogenic, 75 pathogenic, 42 conflicting classifications of pathogenicity, 18 uncertain significance, 17 likely pathogenic, 16 benign, 6 benign/likely benign, 1 likely benign, 1 pathogenic/likely pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
7901	NM_000350.2(ABCA4):c.[1622T>C;3113C>T]		Pathogenic	reviewed by expert panel
1001082	NM_000350.3(ABCA4):c.1019A>C (p.Tyr340Ser)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1062657	NM_000350.3(ABCA4):c.2294GTG[1] (p.Gly766del)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067357	NM_000350.3(ABCA4):c.3522+1G>A	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073468	NM_000350.3(ABCA4):c.1761-2A>G	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184497	NM_000350.3(ABCA4):c.5646G>T (p.Met1882Ile)	ABCA4	Pathogenic	criteria provided, single submitter
1213839	NM_000350.3(ABCA4):c.2576_2579dup (p.Phe861fs)	ABCA4	Pathogenic	criteria provided, single submitter
1275763	NM_000350.3(ABCA4):c.5578C>T (p.Arg1860Trp)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143076	NM_000350.3(ABCA4):c.6119G>A (p.Arg2040Gln)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452669	NM_000350.3(ABCA4):c.2972G>T (p.Gly991Val)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456034	NM_000350.3(ABCA4):c.3304G>T (p.Asp1102Tyr)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456725	NM_000350.3(ABCA4):c.5714+1G>A	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
1476832	NM_000350.3(ABCA4):c.4327C>T (p.Arg1443Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687185	NM_000350.3(ABCA4):c.3470T>G (p.Leu1157Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
1704303	NM_000350.3(ABCA4):c.1698C>G (p.His566Gln)	ABCA4	Pathogenic	criteria provided, single submitter
193580	NM_000350.3(ABCA4):c.1253T>C (p.Phe418Ser)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
198720	NM_000350.3(ABCA4):c.880C>T (p.Gln294Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
212727	NM_000350.3(ABCA4):c.1964T>G (p.Phe655Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236078	NM_000350.3(ABCA4):c.1086T>A (p.Tyr362Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236090	NM_000350.3(ABCA4):c.2160+1G>T	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236095	NM_000350.3(ABCA4):c.2875A>G (p.Thr959Ala)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236096	NM_000350.3(ABCA4):c.2894A>G (p.Asn965Ser)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236100	NM_000350.3(ABCA4):c.3292C>T (p.Arg1098Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236102	NM_000350.3(ABCA4):c.3482G>A (p.Arg1161His)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236110	NM_000350.3(ABCA4):c.4253+5G>A	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236115	NM_000350.3(ABCA4):c.4519G>A (p.Gly1507Arg)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236122	NM_000350.3(ABCA4):c.4773+3A>G	ABCA4	Pathogenic	reviewed by expert panel
236129	NM_000350.3(ABCA4):c.5318C>T (p.Ala1773Val)	ABCA4	Pathogenic	reviewed by expert panel
236144	NM_000350.3(ABCA4):c.6077T>C (p.Leu2026Pro)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236149	NM_000350.3(ABCA4):c.6647C>T (p.Ala2216Val)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 3 · 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
ABCA4	Strong	Autosomal recessive	retinitis pigmentosa 19	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCA4	Orphanet:1872	Cone rod dystrophy
ABCA4	Orphanet:791	Retinitis pigmentosa
ABCA4	Orphanet:827	Stargardt disease

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
ABCA4	HGNC:34	ENSG00000198691	P78363	Retinal-specific phospholipid-transporting ATPase ABCA4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCA4	Retinal-specific phospholipid-transporting ATPase ABCA4	Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leafl…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCA4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR

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
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCA4	164	tissue_specific	marker	pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCA4	1,532

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA4	P78363	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Defective visual phototransduction due to ABCA4 loss of function	1	11420.0×	9e-04	ABCA4
Retinoid cycle disease events	1	2855.0×	9e-04	ABCA4
Diseases associated with visual transduction	1	2855.0×	9e-04	ABCA4
Diseases of the neuronal system	1	2855.0×	9e-04	ABCA4
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.004	ABCA4
Visual phototransduction	1	259.6×	0.006	ABCA4
ABC-family protein mediated transport	1	121.5×	0.012	ABCA4
Sensory Perception	1	95.2×	0.013	ABCA4
Transport of small molecules	1	25.1×	0.044	ABCA4
Disease	1	13.1×	0.076	ABCA4

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
phospholipid transfer to membrane	1	5617.3×	0.002	ABCA4
phototransduction, visible light	1	1296.3×	0.003	ABCA4
retinal metabolic process	1	936.2×	0.003	ABCA4
phospholipid translocation	1	624.1×	0.004	ABCA4
retinoid metabolic process	1	495.6×	0.004	ABCA4
photoreceptor cell maintenance	1	358.6×	0.004	ABCA4
lipid transport	1	263.3×	0.005	ABCA4
transmembrane transport	1	168.5×	0.007	ABCA4
visual perception	1	79.5×	0.013	ABCA4

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
ABCA4	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	1	ABCA4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ABCA4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.