RAB28

Chr 4AR

RAB28, member RAS oncogene family

Also known as: CORD18

NCBI Gene: 9364ENSG00000157869UniProt: P51157

This protein is a small GTPase that regulates intracellular membrane trafficking and is specifically required for shedding and phagocytosis of cone cell outer segment discs in the retina. Biallelic mutations cause cone-rod dystrophy 18, an inherited retinal dystrophy primarily affecting the macula and color vision with autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Cone-rod dystrophy 18MIM #615374
AR
0
Active trials
2
Pubs (1 yr)
89
P/LP submissions
4%
P/LP missense
0.76
LOEUF
LOF
Mechanism· G2P
Clinical Summary— RAB28
🧬
Gene-Disease Validity (ClinGen)
RAB28-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 100 VUS of 288 total submissions
Explore recent and relevant literature in Research Assistant →
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.025
Z-score 2.20
OE 0.36 (0.19–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.38Z-score
OE missense 0.90 (0.77–1.06)
101 obs / 112.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.19–0.76)
0≤0.351.4
Missense OE0.90 (0.77–1.06)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 5 / 13.8Missense obs/exp: 101 / 112.2Syn Z: -0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRAB28-related cone-rod dystrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.86top 5%
GOF
0.83top 10%
LOF
0.2093th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

288 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic11
VUS100
Likely Benign84
Benign10
Conflicting2
71
Pathogenic
11
Likely Pathogenic
100
VUS
84
Likely Benign
10
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
62
0
71
Likely Pathogenic
4
3
4
0
11
VUS
3
80
16
1
100
Likely Benign
0
0
40
44
84
Benign
0
0
10
0
10
Conflicting
—2
Total168313245278

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RAB28 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients