ARL11

Chr 13

ARF like GTPase 11

Also known as: ARLTS1

NCBI Gene: 115761ENSG00000152213UniProt: Q969Q4

The protein is a tumor suppressor related to the ADP-ribosylation factor family that may function in caspase-dependent apoptosis. Mutations in ARL11 cause autosomal recessive neurodevelopmental disorder with intellectual disability, autism spectrum disorder, and dysmorphic features. The gene shows low constraint to loss-of-function mutations, which is consistent with the recessive inheritance pattern observed in affected individuals.

Summary from RefSeq, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

UniProtLeukemia, chronic lymphocytic
0
Active trials
3
Pubs (1 yr)
62
P/LP submissions
0%
P/LP missense
1.89
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ARL11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 41 VUS of 112 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.005
Z-score -0.18
OE 1.12 (0.47–1.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.09Z-score
OE missense 1.02 (0.88–1.19)
121 obs / 118.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.12 (0.47–1.89)
0≤0.351.4
Missense OE1.02 (0.88–1.19)
0≤0.61.4
Synonymous OE0.78
0≤1.21.6
LoF obs/exp: 3 / 2.7Missense obs/exp: 121 / 118.1Syn Z: 1.31
DN
0.6937th %ile
GOF
0.76top 25%
LOF
0.2582th %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

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic2
VUS41
Likely Benign5
60
Pathogenic
2
Likely Pathogenic
41
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
2
0
2
VUS
0
30
11
0
41
Likely Benign
0
2
2
1
5
Benign
0
0
0
0
0
Total032751108

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ARL11 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-wide CRISPR activation screen identifies ARL11 as a sensitivity determinant of PARP inhibitor therapy.
Zhang T et al.·Cancer Gene Ther
2025
Unraveling the Relevance of ARL GTPases in Cutaneous Melanoma Prognosis through Integrated Bioinformatics Analysis.
Brito C et al.·Int J Mol Sci
2021
Comparative genomic analyses of multiple backcross mouse populations suggest SGCG as a novel potential obesity-modifier gene.
Kuhn T et al.·Hum Mol Genet
2022Functional
Identification of novel genes by targeted exome sequencing in Retinoblastoma.
Bisht S et al.·Ophthalmic Genet
2022
Ginsenoside Rg3 synergizes with near-infrared photothermal therapy to suppress prostate cancer progression by inhibiting RAS signaling and enhancing ARL11-mediated macrophage reprogramming.
Zhang H et al.·Int Immunopharmacol
2026
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients