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ARL2BP
ARF like GTPase 2 binding protein
ARL2BP is located on the long (q) arm of chromosome 16, at band 16q13. Arm ratio per GRCh38 - banding schematic.
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Overview
ARL2BP (ARF like GTPase 2 binding protein) is located on chromosome 16 and encodes a relatively small protein of 163 amino acids. This protein functions primarily as a binding partner for ARL2, a regulatory GTPase involved in microtubule dynamics and ciliary assembly. Cilia are hair-like projections on cell surfaces that serve essential roles in sensory perception, including vision, and in establishing the proper left-right arrangement of internal organs during development.
Pathogenic variants in ARL2BP follow an autosomal recessive inheritance pattern, meaning that affected individuals typically inherit altered copies from both parents. The gene has clinical relevance in ophthalmology, particularly for retinal disorders, and is included on several NHS clinical panels for diagnostic evaluation of conditions affecting the eye and organ positioning.
What the gene does
The ARL2BP protein serves as a binding partner and regulator of ARL2, a small GTPase that coordinates microtubule organisation and ciliary assembly. Through its interaction with ARL2, ARL2BP influences the proper formation and function of primary cilia, which are sensory organelles projecting from most mammalian cells. In photoreceptor cells of the retina, cilia are essential for the structural integrity of the outer segment, where light detection occurs.
This protein participates in intracellular trafficking pathways that deliver proteins and membranes to the cilium. The ARL2-ARL2BP complex appears to regulate tubulin cofactor interactions, which are critical for maintaining the microtubule cytoskeleton that forms the ciliary axoneme. Disruption of these processes can impair ciliary function, leading to defects in sensory perception and developmental signalling pathways that depend on ciliary activity. The protein's role extends beyond the retina, as cilia are also required for establishing left-right asymmetry during embryonic development.
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Chromosome location
ARL2BP is located on the long arm of chromosome 16 at position 16q13. This chromosomal region contains several genes involved in developmental processes and sensory function. The gene's compact coding sequence reflects the relatively small size of the encoded protein. Specific details regarding the total number of exons and transcript variants have not been extensively characterised in publicly available databases.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The ARL2BP protein comprises 163 amino acids and lacks well-annotated functional domains in current structural databases. Its molecular function is understood primarily through its binding interaction with ARL2 GTPase, though the precise regions mediating this interaction have not been mapped to specific structured domains. The protein's compact size suggests it may function as a relatively simple adaptor or regulatory module.
Key variants
Pathogenic variants in ARL2BP are inherited in an autosomal recessive manner, requiring changes in both gene copies to cause disease. The variant spectrum includes loss-of-function changes such as nonsense mutations and frameshift deletions that disrupt protein production. Missense variants affecting critical residues involved in ARL2 binding have also been reported. The clinical severity and specific manifestations can vary depending on the nature of the variants present, though retinal involvement is a common feature.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.207+1G>A | - | Pathogenic | ★★☆☆ | ARL2BP-related disorder |
c.139_143dup | p.Tyr48Ter | Pathogenic | ★☆☆☆ | not provided |
c.191del | p.Pro64fs | Pathogenic | ★☆☆☆ | not provided |
c.207C>A | p.Tyr69Ter | Pathogenic | ★☆☆☆ | not provided |
c.235G>T | p.Glu79Ter | Pathogenic | ★☆☆☆ | not provided |
c.33_36del | p.Phe13fs | Pathogenic | ★☆☆☆ | Retinitis pigmentosa |
c.37_38del | p.Phe13fs | Pathogenic | ★☆☆☆ | Retinal dystrophy |
c.97_98dup | p.Met33fs | Pathogenic | ★☆☆☆ | not provided |
c.22_23del | p.Ser8fs | Pathogenic | - | Retinitis pigmentosa with or without situs inversus |
c.294-1G>C | - | Pathogenic | - | Retinitis pigmentosa with or without situs inversus |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in ARL2BP are associated with autosomal recessive conditions primarily affecting the retina and, in some cases, organ positioning. Retinal dystrophies caused by ARL2BP variants typically involve progressive degeneration of photoreceptor cells, leading to vision impairment. Some affected individuals may present with laterality defects, where internal organs develop abnormal left-right positioning, reflecting the gene's role in ciliary signalling during embryonic development. The phenotypic spectrum ranges from isolated retinal disease to syndromic presentations involving multiple organ systems.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic ARL2BP variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
ARL2BP is included on three NHS Genomic Medicine Service panels as a green gene, indicating strong evidence for its clinical validity. The gene appears on the Retinal disorders panel (R32), reflecting its established role in inherited retinal disease. It is also listed on the Fetal anomalies panel (R21) and the Laterality disorders and isomerism panel (R139), acknowledging its association with developmental abnormalities affecting organ positioning. This panel membership supports the use of ARL2BP testing in UK clinical diagnostic pathways for patients presenting with retinal degeneration or laterality defects.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What inheritance pattern does ARL2BP follow?
ARL2BP variants are inherited in an autosomal recessive pattern, meaning an individual must inherit a pathogenic variant from both parents to develop an associated condition. Carriers with one variant typically do not show symptoms.
How does ARL2BP relate to retinal health?
The ARL2BP protein supports ciliary function in photoreceptor cells, which are essential for light detection in the retina. Disruption of this function can lead to progressive retinal degeneration and vision loss.
Why is ARL2BP included on laterality disorder panels?
Primary cilia, which depend on ARL2BP function, play a crucial role in establishing left-right body asymmetry during embryonic development. Variants affecting ciliary function can therefore result in abnormal organ positioning.