ARL13B

Chr 3AR

ARF like GTPase 13B

Also known as: ARL2L1, JBTS8

This gene encodes a cilium-specific GTPase that controls the microtubule-based ciliary axoneme structure and is required for neural tube patterning and cerebral cortex development. Mutations cause Joubert syndrome 8, a ciliopathy characterized by cerebellar vermis hypoplasia and brainstem malformation, with autosomal recessive inheritance. The gene shows very low tolerance to loss-of-function variants (pLI near 0), suggesting that complete loss of function may be incompatible with survival in the heterozygous state.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.041 OMIM phenotype
Clinical SummaryARL13B
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Gene-Disease Validity (ClinGen)
Joubert syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — ARL13B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.42
OE 0.69 (0.471.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.911.13)
230 obs / 227.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.471.04)
00.351.4
Missense OE1.01 (0.911.13)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 17 / 24.6Missense obs/exp: 230 / 227.5Syn Z: -0.27
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveARL13B-related Joubert syndromeOTHERAR

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

DN
0.7033th %ile
GOF
0.81top 10%
LOF
0.3164th %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

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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