ARL13B

Chr 3AR

ARF like GTPase 13B

Also known as: ARL2L1, JBTS8

NCBI Gene: 200894ENSG00000169379UniProt: Q3SXY8

This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia. Mutations in this gene are the cause of Joubert syndrome 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Joubert syndrome 8MIM #612291
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ARL13B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.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.
1.04LOEUF
pLI 0.000
Z-score 1.42
OE 0.69 (0.47–1.04)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.06Z-score
OE missense 1.01 (0.91–1.13)
230 obs / 227.5 exp
Tolerant

Tolerant to missense variation

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.0.69 (0.47–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.91–1.13)
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.1.04
0≤1.21.6
LoF obs/exp: 17 / 24.6Missense obs/exp: 230 / 227.5Syn Z: -0.27

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ARL13B · protein map & ClinVar variants

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

Gene2Phenotype Curations

ARL13B-related Joubert syndrome

definitive
ARUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Joubert syndrome 8

MIM #612291

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Knocking out ARL13B completely abolishes primary ciliogenesis in cell lines.
Mahajan D et al.·Sci Rep
2025
Optic vesicle morphogenesis requires primary cilia.
Fiore L et al.·Dev Biol
2020
Arl13b Promotes Gastric Tumorigenesis by Regulating Smo Trafficking and Activation of the Hedgehog Signaling Pathway.
Shao J et al.·Cancer Res
2017
Ciliogenesis mechanisms mediated by PAK2-ARL13B signaling in brain endothelial cells is responsible for vascular stability.
Thirugnanam K et al.·Biochem Pharmacol
2022Functional
Novel compound heterozygous variants in ARL13B lead to Joubert syndrome.
Lin Z et al.·J Cell Physiol
2024
Biallelic pathogenic TULP3 variants presenting as neonatal cholestasis, liver fibrosis and neurological manifestations.
Li JQ et al.·J Med Genet
2025Case report
Joubert syndrome and related disorders.
Paprocka J et al.·Neurol Neurochir Pol
2012Review
Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E.
Nozaki S et al.·J Cell Sci
2017
Identification of a novel ARL13B variant in a Joubert syndrome-affected patient with retinal impairment and obesity.
Thomas S et al.·Eur J Hum Genet
2015Case report
MKS1 regulates ciliary INPP5E levels in Joubert syndrome.
Slaats GG et al.·J Med Genet
2016
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools