ARL2

Chr 11AD

ARF like GTPase 2

Also known as: ARFL2, MRCS1

NCBI Gene: 402ENSG00000213465UniProt: P36404

This gene encodes a small GTP-binding protein of the RAS superfamily which functions as an ADP-ribosylation factor (ARF). The encoded protein is one of a functionally distinct group of ARF-like genes. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1MIM #619082
AD
40
ClinVar variants
9
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— ARL2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 26 VUS of 40 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.
1.00LOEUF
pLI 0.021
Z-score 1.58
OE 0.44 (0.21–1.00)
Tolerant

Typical tolerance to LoF variation

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.
1.05Z-score
OE missense 0.72 (0.60–0.87)
82 obs / 113.5 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.0.44 (0.21–1.00)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.60–0.87)
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.1.08
0≤1.21.6
LoF obs/exp: 4 / 9.2Missense obs/exp: 82 / 113.5Syn Z: -0.42

ClinVar Variant Classifications

40 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS26
Likely Benign4
7
Pathogenic
2
Likely Pathogenic
26
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
6
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
23
3
0
26
Likely Benign
1
2
0
1
4
Benign
0
0
0
0
0
Total12611139

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

View in ClinVar →

Protein Context — Lollipop Plot

ARL2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ARL2-related microcornea, rod-cone dystrophy, cataract, and posterior staphyloma (MRCS) syndrome

strong
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1

MIM #619082

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of mutations associated with congenital cataracts in nineteen Chinese families.
Sun HS et al.·BMC Ophthalmol
2025
ADP ribosylation factor like 2 (Arl2) regulates breast tumor aggressivity in immunodeficient mice.
Beghin A et al.·PLoS One
2009
MicroRNA-195 targets ADP-ribosylation factor-like protein 2 to induce apoptosis in human embryonic stem cell-derived neural progenitor cells.
Zhou Y et al.·Cell Death Dis
2013
Whole-exome sequencing identified ARL2 as a novel candidate gene for MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome.
Cai XB et al.·Clin Genet
2019Case report
Long non-coding RNA SNHG3, induced by IL-6/STAT3 transactivation, promotes stem cell-like properties of gastric cancer cells by regulating the miR-3619-5p/ARL2 axis.
Sun B et al.·Cell Oncol (Dordr)
2021
Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.
Miyake N et al.·Am J Hum Genet
2016
Diversity of TITAN functions in Arabidopsis seed development.
Tzafrir I et al.·Plant Physiol
2002
Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2.
Wang Y et al.·Clin Sci (Lond)
2019
Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex.
Veltel S et al.·FEBS Lett
2008
A case of Joubert syndrome caused by novel compound heterozygous variants in the TMEM67 gene.
Kozina AA et al.·J Int Med Res
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
DDX60 protects ischemic myocardial injury and heart dysfunction by improving mitochondrial function via promoting Arl2 mRNA translation.
Yuan T et al.·Cell Mol Life Sci
2025🔓 Open Access
Arl2 GTPase associates with the centrosomal protein Cdk5rap2 to regulate cortical development via microtubule organization.
Ma D et al.·PLoS Biol
2024🔓 Open Access
Retraction Note: MiR-195-5p inhibits the cell migration and invasion of cervical carcinoma through suppressing ARL2.
Pan SS et al.·Eur Rev Med Pharmacol Sci
2023
Long Non-Coding RNA ZSCAN16-AS1 Promotes the Malignant Progression of Melanoma Through Regulating the miR-503-5p/ARL2 Axis.
Zhao Y et al.·Clin Cosmet Investig Dermatol
2023🔓 Open Access
Arf-like Protein 2 (ARL2) Controls Microtubule Neogenesis during Early Postnatal Photoreceptor Development.
Gerstner CD et al.·Cells
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools