ARL6

Chr 3ARDigenic recessive

ARF like GTPase 6

Also known as: BBS3, RP55

NCBI Gene: 84100 ENSG00000113966 UniProt: Q9H0F7 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the ARF-like (ADP ribosylation factor-like) sub-family of the ARF family of GTP-binding proteins which are involved in regulation of intracellular traffic. Mutations in this gene are associated with Bardet-Biedl syndrome (BBS). A vision-specific transcript, encoding long isoform BBS3L, has been described (PMID: 20333246). [provided by RefSeq, Apr 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Bardet-Biedl syndrome 1, modifier of}MIM #209900

ARDigenic recessive

Bardet-Biedl syndrome 3MIM #600151

Retinitis pigmentosa 55MIM #613575

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ciliopathy · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

LOF

Mechanism· G2P

📖

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 OE?0.44 (0.23–0.92)

0≤0.351.4

Missense OE?0.84 (0.70–1.01)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 11.5Missense obs/exp: 81 / 96.3Syn Z: 0.18

Background carrier burden — how many people carry a rare variant somewhere in ARL6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 480

210 rare PASS variants

Rare truncating (LoF)

1 in 5,700

37 rare PASS variants

Rare synonymous (reference)

1 in 850

69 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARL6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 680	1 in 4,700
South Asian	~43k	1 in 580	1 in 5,300
Remaining (unassigned)	~30k	1 in 410	1 in 5,300
European (Finnish)	~27k	1 in 890	none seen
Admixed American	~22k	1 in 410	≈ 1 in 5,600
African / African American	~21k	1 in 240	≈ 1 in 8,400
East Asian	~20k	1 in 650	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 870	none seen
Middle Eastern	~2,883	1 in 580	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓