ARL6

Chr 3ARDigenic recessive

ARF like GTPase 6

Also known as: BBS3, RP55

NCBI Gene: 84100ENSG00000113966UniProt: Q9H0F7OMIM: 608845

The protein regulates membrane protein trafficking to primary cilia and controls assembly of the BBSome complex, which is essential for proper ciliary function and signaling pathways including sonic hedgehog and Wnt. Mutations cause Bardet-Biedl syndrome, a multisystem ciliopathy affecting vision, kidney function, obesity, and intellectual development, as well as isolated retinitis pigmentosa. Inheritance is autosomal recessive.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/Digenic recessiveLOEUF 0.923 OMIM phenotypes
Clinical Summary— ARL6
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Gene-Disease Validity (ClinGen)
ciliopathy · 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
71 unique Pathogenic / Likely Pathogenic· 115 VUS of 334 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ARL6
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
0.92LOEUF
pLI 0.010
Z-score 1.77
OE 0.44 (0.23–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.56Z-score
OE missense 0.84 (0.70–1.01)
81 obs / 96.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.23–0.92)
0≤0.351.4
Missense OE0.84 (0.70–1.01)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 5 / 11.5Missense obs/exp: 81 / 96.3Syn Z: 0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveARL6-related Bardet-Biedl syndromeLOFAR
strongARL6-related retinal dystrophyOTHERAR

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

DN
0.78top 25%
GOF
0.72top 25%
LOF
0.2679th %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

334 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic33
VUS115
Likely Benign119
Benign11
Conflicting9
38
Pathogenic
33
Likely Pathogenic
115
VUS
119
Likely Benign
11
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
6
13
0
38
Likely Pathogenic
14
10
8
1
33
VUS
4
79
32
0
115
Likely Benign
0
3
65
51
119
Benign
0
0
11
0
11
Conflicting
—9
Total379812952325

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

View in ClinVar →

Protein Context — Lollipop Plot

ARL6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients