Cone-rod dystrophy 18

disease

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Also known as cone-rod dystrophy caused by mutation in RAB28cone-rod dystrophy type 18CORD18RAB28 cone-rod dystrophy

Summary

Cone-rod dystrophy 18 (MONDO:0014153) is a disease caused by RAB28 (GenCC Definitive), with 1 cohort gene.

At a glance

Causal gene: RAB28 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 18
Mondo ID	MONDO:0014153
OMIM	615374
DOID	DOID:0111024
UMLS	C3809299
MedGen	815629
GARD	0015953
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 18 · cone-rod dystrophy caused by mutation in RAB28 · cone-rod dystrophy type 18 · CORD18 · RAB28 cone-rod dystrophy

Data availability: 12 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 › cone-rod dystrophy › cone-rod dystrophy 18

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

12 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 uncertain significance, 3 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
225878	NM_001017979.3(RAB28):c.172+1G>C	RAB28	Pathogenic	criteria provided, single submitter
225879	NM_004249.4(RAB28):c.651T>G (p.Cys217Trp)	RAB28	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3363160	NM_001017979.3(RAB28):c.247_248dup (p.Tyr84fs)	RAB28	Pathogenic	criteria provided, single submitter
60754	NM_001017979.3(RAB28):c.565C>T (p.Gln189Ter)	RAB28	Pathogenic	criteria provided, single submitter
60755	NM_001017979.3(RAB28):c.409C>T (p.Arg137Ter)	RAB28	Pathogenic	no assertion criteria provided
3383939	NC_000004.12:g.13369348_13485964del	LOC111828517	Likely pathogenic	no assertion criteria provided
4849230	NM_001017979.3(RAB28):c.128_131del (p.Gln43fs)	RAB28	Likely pathogenic	criteria provided, single submitter
623218	NM_001017979.3(RAB28):c.355_356del (p.Glu119fs)	RAB28	Likely pathogenic	criteria provided, multiple submitters, no conflicts
933988	NM_004249.4(RAB28):c.607G>T (p.Glu203Ter)	RAB28	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1302545	NM_001017979.3(RAB28):c.68C>T (p.Ser23Phe)	LOC111828517	Uncertain significance	criteria provided, multiple submitters, no conflicts
1172724	NM_001017979.3(RAB28):c.202G>C (p.Asp68His)	RAB28	Uncertain significance	criteria provided, multiple submitters, no conflicts
1960852	NM_001017979.3(RAB28):c.328GTG[1] (p.Val111del)	RAB28	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RAB28	Definitive	Autosomal recessive	cone-rod dystrophy 18	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAB28	Orphanet:1872	Cone rod dystrophy

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
RAB28	HGNC:9768	ENSG00000157869	P51157	Ras-related protein Rab-28	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAB28	Ras-related protein Rab-28	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

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)
RAB28	Other/Unknown	no		Small_GTPase, Small_GTP-bd, 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
endothelial cell	1
germinal epithelium of ovary	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAB28	284	ubiquitous	marker	tibia, germinal epithelium of ovary, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAB28	1,563

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAB28	P51157	2

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
intracellular protein transport	1	64.8×	0.015	RAB28

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
RAB28	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	RAB28

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)
RAB28	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RAB28