ARL6IP1
Chr 16ARARL6 interacting reticulophagy regulator 1
Also known as: AIP1, ARL6IP, ARMER, SPG61
The protein regulates glutamate transport by enhancing SLC1A1/EAAC1 transporter activity, forms and stabilizes endoplasmic reticulum tubules, and negatively regulates apoptosis. Mutations cause spastic paraplegia 61, an autosomal recessive disorder affecting the corticospinal tracts and leading to progressive lower limb spasticity. The gene shows relatively low constraint to loss-of-function variation (pLI 0.02, LOEUF 0.78).
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ARL6IP1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools