ARL10

Chr 5

ARF like GTPase 10

Also known as: ARL10A

NCBI Gene: 285598 ENSG00000175414 UniProt: Q8N8L6 OMIM: 612405

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.

OMIM ResearchSummary from RefSeq

Predicted to enable GTP binding activity and GTPase activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.23

Clinical Summary— ARL10

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.001

Z-score 1.08

OE 0.62 (0.34–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.98Z-score

OE missense 0.75 (0.64–0.89)

94 obs / 124.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.34–1.23)

0≤0.351.4

Missense OE?0.75 (0.64–0.89)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 6 / 9.6Missense obs/exp: 94 / 124.9Syn Z: -0.81

This gene — mechanism propensity

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.