RAB5C
Chr 17RAB5C, member RAS oncogene family
Also known as: L1880, RAB5CL, RAB5L, RABL
Members of the Rab protein family are small GTPases of the Ras superfamily that are thought to ensure fidelity in the process of docking and/or fusion of vesicles with their correct acceptor compartment (Han et al., 1996 [PubMed 8646882]).[supplied by OMIM, Nov 2010]
Clinical Summary— RAB5C
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 27 VUS of 34 total submissions
Some data sources returned errors (1)
ensembl: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
LoF intolerant — likely haploinsufficient
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.
0.36LOEUF
pLI 0.937
Z-score 3.11
OE 0.08 (0.03–0.36)
More LoF-intolerant than ~75% of genes
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.
1.42Z-score
OE missense 0.67 (0.57–0.79)
98 obs / 146.2 exp
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.0.08 (0.03–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.57–0.79)
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.0.96
0≤1.21.6
LoF obs/exp: 1 / 13.2Missense obs/exp: 98 / 146.2Syn Z: 0.25
ClinVar Variant Classifications
34 submitted variants in ClinVar
Classification Summary
Pathogenic6
VUS27
Benign1
6
Pathogenic
27
VUS
1
Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 6 | 0 | 6 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 1 | 24 | 2 | 0 | 27 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 1 | 24 | 8 | 1 | 34 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAB5C · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
RAB5C-related neurodevelopmental disorder
moderatestop gainedmissense variantinframe insertion
Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
RAS-ASSOCIATED PROTEIN RAB5C; RAB5C
MIM #604037 · *
External Resources
Links to major genomics databases and tools
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Macrocephaly and developmental delay caused by missense variants in RAB5C.
Koop K et al.·Hum Mol Genet
2023
Extracellular Vesicle Proteome Analysis Improves Diagnosis of Recurrence in Triple-Negative Breast Cancer.
Hyon JY et al.·J Extracell Vesicles
2025
Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation.
Li J et al.·J Virol
2020
Endocytic Markers Associated with the Internalization and Processing of Aspergillus fumigatus Conidia by BEAS-2B Cells.
Clark HR et al.·mSphere
2019
Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.
Sabater-Lleal M et al.·Circulation
2019Meta-analysis
Weighted gene co-expression network analysis to define pivotal modules and genes in diabetic heart failure.
Liang W et al.·Biosci Rep
2020
Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines.
Linnane E et al.·Nucleic Acids Res
2019Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
RAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.
Reventun P et al.·Arterioscler Thromb Vasc Biol
2026
Prolonged visual experience accelerates developmental synaptic downscaling via epigenetic regulation and Rab5c mediated AMPA receptor trafficking.
Zheng L et al.·Commun Biol
2026Open Access
Rab5c promotes RSV and ADV replication by autophagy in respiratory epithelial cells.
Wang X et al.·Virus Res
2024Open Access
Effects of miR-145 targeting rab5c and regulating MAPK / ERK signaling pathway on proliferation and invasion of thyroid papillary carcinoma cells.
Wen X et al.·Cell Mol Biol (Noisy-le-grand)
2023
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Enhancing the chondrogenic potential of chondrogenic progenitor cells by deleting RAB5C
Janssen JN et al.·iScience
2021
RAB5C, SYNJ1, and RNF19B promote male ankylosing spondylitis by regulating immune cell infiltration
Zhang D et al.·Ann Transl Med
2021
Identification of Potential Protein Targets in Extracellular Vesicles Isolated from Chemotherapy-Treated Ovarian Cancer Cells
Chan CY et al.·Curr Issues Mol Biol
2023
RAB5c controls the assembly of non-canonical autophagy machinery to promote phagosome maturation and microbicidal function of macrophages
Freitas-Filho EG et al.·bioRxiv
2025
RAB5C, a new mRNA binding target of HuR, regulates breast cancer cell proliferation.
Wang Z et al.·Cell Biol Int
2023
Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-beta signaling by recruiting Rab5c
Li YM et al.·Cancer Cell Int
2022
Top 6 full-text resultsSearch PubTator3 ↗
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools