RAB23

Chr 6AR

RAB23, member RAS oncogene family

Also known as: CRPT1, HSPC137

NCBI Gene: 51715ENSG00000112210UniProt: Q9ULC3

This gene encodes a small GTPase of the Ras superfamily. Rab proteins are involved in the regulation of diverse cellular functions associated with intracellular membrane trafficking, including autophagy and immune response to bacterial infection. The encoded protein may play a role in central nervous system development by antagonizing sonic hedgehog signaling. Disruption of this gene has been implicated in Carpenter syndrome as well as cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Carpenter syndrome 1MIM #201000
AR
324
ClinVar variants
41
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— RAB23
🧬
Gene-Disease Validity (ClinGen)
RAB23-related Carpenter syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 109 VUS of 324 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.006
Z-score 2.02
OE 0.42 (0.23–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.32Z-score
OE missense 0.92 (0.79–1.07)
112 obs / 121.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.23–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.79–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 6 / 14.2Missense obs/exp: 112 / 121.9Syn Z: 0.10

ClinVar Variant Classifications

324 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic14
VUS109
Likely Benign150
Benign14
Conflicting10
27
Pathogenic
14
Likely Pathogenic
109
VUS
150
Likely Benign
14
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
1
16
0
27
Likely Pathogenic
10
0
4
0
14
VUS
2
66
41
0
109
Likely Benign
0
3
68
79
150
Benign
0
0
13
1
14
Conflicting
—10
Total227014280324

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB23 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RAB23-related acrocephalopolysyndactyly

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Carpenter syndrome 1

MIM #201000

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rab23 and developmental disorders.
Hor CHH et al.·Rev Neurosci
2018Review
Structural basis for Rab23 activation and a loss-of-function mutation in Carpenter syndrome.
Chau YY et al.·J Biol Chem
2025
RAB23 loss-of-function mutation causes context-dependent ciliopathy in Carpenter syndrome.
Leong WY et al.·PLoS Genet
2025
Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1.
Wang M et al.·Tumour Biol
2016
The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients.
Watts LM et al.·Eur J Hum Genet
2024Case report
Expansion of the phenotypic and mutational spectrum of Carpenter syndrome.
Khairat R et al.·Eur J Med Genet
2022Case report
Biomarker of Pulmonary Inflammatory Response in LUAD: miR-584-5p Targets RAB23 to Suppress Inflammation Induced by LPS in A549 Cells.
Yang E et al.·Protein Pept Lett
2023
Open brain gene product Rab23: expression pattern in the adult mouse brain and functional characterization.
Guo A et al.·J Neurosci Res
2006Functional
Genetic basis of potential therapeutic strategies for craniosynostosis.
Melville H et al.·Am J Med Genet A
2010Review
Carpenter syndrome: a review for the craniofacial surgeon.
Kadakia S et al.·J Craniofac Surg
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools