Retinitis pigmentosa 83

disease

On this page

Also known as RP83

Summary

Retinitis pigmentosa 83 (MONDO:0032577) is a disease caused by ARL3 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ARL3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 83
Mondo ID	MONDO:0032577
OMIM	618173
DOID	DOID:0112140
UMLS	C4748536
MedGen	1648404
GARD	0016298
Is cancer (heuristic)	no

Also known as: RP83

Data availability: 5 ClinVar variants · 4 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 83

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
587684	NM_004311.4(ARL3):c.269A>G (p.Tyr90Cys)	ARL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009318	NM_004311.4(ARL3):c.472T>G (p.Cys158Gly)	ARL3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1327584	NM_004311.4(ARL3):c.86G>T (p.Gly29Val)	ARL3	Uncertain significance	criteria provided, single submitter
3237172	NM_004311.4(ARL3):c.199G>A (p.Asp67Asn)	ARL3	Uncertain significance	criteria provided, single submitter
1192445	NM_004311.4(ARL3):c.-75C>T	ARL3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
ARL3	Strong	Autosomal dominant	retinitis pigmentosa 83	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARL3	Orphanet:475	Isolated Joubert syndrome
ARL3	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
ARL3	HGNC:694	ENSG00000138175	P36405	ADP-ribosylation factor-like protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARL3	ADP-ribosylation factor-like protein 3	Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP).

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)
ARL3	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase

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
epithelium of bronchus	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARL3	299	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARL3	2,651

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARL3	P36405	92.73

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
Trafficking of myristoylated proteins to the cilium	1	2284.0×	0.002	ARL3
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	ARL3
Cilium Assembly	1	108.8×	0.012	ARL3
Organelle biogenesis and maintenance	1	66.0×	0.015	ARL3

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
photoreceptor cell development	1	4213.0×	0.002	ARL3
protein localization to ciliary membrane	1	3370.4×	0.002	ARL3
post-Golgi vesicle-mediated transport	1	1053.2×	0.004	ARL3
Golgi to plasma membrane transport	1	561.7×	0.004	ARL3
intraciliary transport	1	561.7×	0.004	ARL3
protein localization to cilium	1	401.2×	0.005	ARL3
mitotic cytokinesis	1	259.3×	0.007	ARL3
small GTPase-mediated signal transduction	1	183.2×	0.007	ARL3
smoothened signaling pathway	1	181.2×	0.007	ARL3
kidney development	1	140.4×	0.009	ARL3
cilium assembly	1	73.6×	0.015	ARL3
protein transport	1	43.9×	0.023	ARL3

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
ARL3	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	ARL3

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)
ARL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ARL3