ARL17B

Chr 17

ARF like GTPase 17B

Also known as: ARL17

NCBI Gene: 100506084 ENSG00000228696 UniProt: I3L3L1

Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Active trials

Pathogenic / LP

139

ClinVar variants

Pubs (1 yr)

0.9

Missense Z

1.83

LOEUF

Clinical Summary— ARL17B

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

📋

ClinVar Variants

14 Pathogenic / Likely Pathogenic· 78 VUS of 139 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.83LOEUF

pLI 0.336

Z-score 0.66

OE 0.00 (0.00–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.92Z-score

OE missense 0.00 (0.00–0.45)

0 obs / 6.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–1.83)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.00 (0.00–0.45)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.00

0≤1.21.6

LoF obs/exp: 0 / 0.5Missense obs/exp: 0 / 6.6Syn Z: 1.20

0.76top 25%

GOF

0.5464th %ile

LOF

0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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.