Retinitis pigmentosa 55

Summary

Retinitis pigmentosa 55 (MONDO:0013312) is a disease caused by ARL6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ARL6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 221

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 55
Mondo ID	MONDO:0013312
OMIM	613575
DOID	DOID:0110370
UMLS	C3150808
MedGen	462158
GARD	0015677
Is cancer (heuristic)	no

Also known as: ARL6 retinitis pigmentosa · retinitis pigmentosa 55 · retinitis pigmentosa caused by mutation in ARL6 · retinitis pigmentosa type 55 · RP55

Data availability: 221 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 55

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 54, retinitis pigmentosa 51, 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

221 retrieved; paginated sample, class counts are floors:

105 likely benign, 64 uncertain significance, 21 pathogenic, 15 likely pathogenic, 6 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 2 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028925	NM_001278293.3(ARL6):c.228C>G (p.Tyr76Ter)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075539	NM_001278293.3(ARL6):c.4G>T (p.Gly2Ter)	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
1076146	NC_000003.11:g.(?97194196)(97510809_?)del	ARL6	Pathogenic	criteria provided, single submitter
1446585	NM_001278293.3(ARL6):c.1A>G (p.Met1Val)	ARL6	Pathogenic	criteria provided, single submitter
1457182	NC_000003.11:g.(?97498983)(97516893_?)del	ARL6	Pathogenic	criteria provided, single submitter
1459992	NC_000003.11:g.(?97486952)(97516893_?)del	ARL6	Pathogenic	criteria provided, single submitter
1805423	NM_001278293.3(ARL6):c.534A>G (p.Gln178=)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2040	NM_001278293.3(ARL6):c.364C>T (p.Arg122Ter)	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
2041	NM_001278293.3(ARL6):c.506G>C (p.Gly169Ala)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2042	NM_001278293.3(ARL6):c.92C>T (p.Thr31Met)	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
2044	NM_001278293.3(ARL6):c.92C>G (p.Thr31Arg)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2071999	NM_001278293.3(ARL6):c.469del (p.Trp157fs)	ARL6	Pathogenic	criteria provided, single submitter
2102573	NM_001278293.3(ARL6):c.262C>T (p.Gln88Ter)	ARL6	Pathogenic	criteria provided, single submitter
2115026	NM_001278293.3(ARL6):c.127C>T (p.Gln43Ter)	ARL6	Pathogenic	criteria provided, single submitter
2940871	NM_001278293.3(ARL6):c.228C>A (p.Tyr76Ter)	ARL6	Pathogenic	criteria provided, single submitter
2942834	NM_001278293.3(ARL6):c.406_409del (p.Asp136fs)	ARL6	Pathogenic	criteria provided, single submitter
2943163	NM_001278293.3(ARL6):c.188T>A (p.Leu63Ter)	ARL6	Pathogenic	criteria provided, single submitter
2950730	NM_001278293.3(ARL6):c.66C>A (p.Cys22Ter)	ARL6	Pathogenic	criteria provided, single submitter
2950809	NM_001278293.3(ARL6):c.252T>G (p.Tyr84Ter)	ARL6	Pathogenic	criteria provided, single submitter
3069201	NM_001278293.3(ARL6):c.255-2A>T	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
3246908	NC_000003.11:g.(?97486952)(97487094_?)del	ARL6	Pathogenic	criteria provided, single submitter
438186	NM_001278293.3(ARL6):c.281T>C (p.Ile94Thr)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
576069	NM_001278293.3(ARL6):c.185+1G>C	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
68064	NM_001278293.3(ARL6):c.272T>C (p.Ile91Thr)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
832088	NC_000003.12:g.(?97768108)(97768230_?)del	ARL6	Pathogenic	criteria provided, single submitter
861499	NM_001278293.3(ARL6):c.506del (p.Gly169fs)	ARL6	Pathogenic	criteria provided, single submitter
977510	NM_001278293.3(ARL6):c.373dup (p.Ile125fs)	ARL6	Pathogenic	criteria provided, single submitter
1180769	NM_001278293.3(ARL6):c.349+1G>A	ARL6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1483429	NM_001278293.3(ARL6):c.479+1G>A	ARL6	Likely pathogenic	criteria provided, single submitter
191178	NM_001278293.3(ARL6):c.362G>A (p.Arg121His)	ARL6	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
ARL6	Strong	Autosomal recessive	retinitis pigmentosa 55	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARL6	Orphanet:110	Bardet-Biedl syndrome
ARL6	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
ARL6	HGNC:13210	ENSG00000113966	Q9H0F7	ADP-ribosylation factor-like protein 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARL6	ADP-ribosylation factor-like protein 6	Involved in membrane protein trafficking at the base of the ciliary organelle.

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)
ARL6	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF

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
Brodmann (1909) area 23	1
endothelial cell	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARL6	228	ubiquitous	marker	oviduct epithelium, Brodmann (1909) area 23, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARL6	1,811

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARL6	Q9H0F7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.008	ARL6
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	ARL6
Cilium Assembly	1	108.8×	0.012	ARL6
Organelle biogenesis and maintenance	1	66.0×	0.015	ARL6

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 transport from ciliary membrane to plasma membrane	1	5617.3×	0.002	ARL6
protein localization to non-motile cilium	1	4213.0×	0.002	ARL6
protein polymerization	1	991.3×	0.004	ARL6
melanosome transport	1	766.0×	0.004	ARL6
retina layer formation	1	648.1×	0.004	ARL6
regulation of smoothened signaling pathway	1	624.1×	0.004	ARL6
protein localization to cilium	1	401.2×	0.006	ARL6
protein targeting to membrane	1	295.6×	0.007	ARL6
determination of left/right symmetry	1	255.3×	0.007	ARL6
fat cell differentiation	1	181.2×	0.009	ARL6
Wnt signaling pathway	1	99.7×	0.014	ARL6
vesicle-mediated transport	1	96.3×	0.014	ARL6
brain development	1	79.5×	0.014	ARL6
visual perception	1	79.5×	0.014	ARL6
cilium assembly	1	73.6×	0.014	ARL6
intracellular protein transport	1	64.8×	0.015	ARL6

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
ARL6	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	ARL6

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)
ARL6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.