ARL10

Chr 5

ARF like GTPase 10

Also known as: ARL10A

ARL10 encodes a GTPase that binds GTP and localizes to mitochondria. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and dystonia. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.23
Clinical SummaryARL10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.001
Z-score 1.08
OE 0.62 (0.341.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.98Z-score
OE missense 0.75 (0.640.89)
94 obs / 124.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.341.23)
00.351.4
Missense OE0.75 (0.640.89)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 6 / 9.6Missense obs/exp: 94 / 124.9Syn Z: -0.81
DN
0.6357th %ile
GOF
0.6833th %ile
LOF
0.2871th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

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

ARL10 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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