ARL13B

Chr 3AR

ARF like GTPase 13B

Also known as: ARL2L1, JBTS8

NCBI Gene: 200894 ENSG00000169379 UniProt: Q3SXY8 OMIM: 608922

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.041 OMIM phenotype

Clinical Summary— ARL13B

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Gene-Disease Validity (ClinGen)

Joubert syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

44 unique Pathogenic / Likely Pathogenic· 211 VUS of 466 total submissions

Explore recent and relevant literature in Research Assistant →

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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

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.06Z-score

OE missense 1.01 (0.91–1.13)

230 obs / 227.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.47–1.04)

0≤0.351.4

Missense OE?1.01 (0.91–1.13)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 17 / 24.6Missense obs/exp: 230 / 227.5Syn Z: -0.27

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveARL13B-related Joubert syndromeOTHERAR

This gene — mechanism propensity

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

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

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic29

VUS211

Likely Benign161

Benign14

Conflicting23

Pathogenic

Likely Pathogenic

211

VUS

161

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	2	2	0	15
Likely Pathogenic	24	4	1	0	29
VUS	2	192	15	2	211
Likely Benign	0	5	91	65	161
Benign	0	4	10	0	14
Conflicting	—				23
Total	37	207	119	67	453

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap ARL13B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →