ARL2

Chr 11

ARF like GTPase 2

Also known as: ARFL2, MRCS1

NCBI Gene: 402 ENSG00000213465 UniProt: P36404

This gene encodes ARL2, a small GTP-binding protein that regulates microtubule formation, centrosome integrity, and mitochondrial function. Mutations cause microcornea with rod-cone dystrophy, cataract, and posterior staphyloma, primarily affecting ocular development and retinal function. Inheritance is autosomal dominant.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMicrocornea, rod-cone dystrophy, cataract, and posterior staphyloma 1

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.021

Z-score 1.58

OE 0.44 (0.21–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.05Z-score

OE missense 0.72 (0.60–0.87)

82 obs / 113.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.21–1.00)

0≤0.351.4

Missense OE?0.72 (0.60–0.87)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 9.2Missense obs/exp: 82 / 113.5Syn Z: -0.42

Background carrier burden — how many people carry a rare variant somewhere in ARL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

228 rare PASS variants

Rare truncating (LoF)

1 in 5,900

30 rare PASS variants

Rare synonymous (reference)

1 in 500

119 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 390	1 in 5,900
South Asian	~43k	1 in 380	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 220	1 in 4,200
European (Finnish)	~27k	1 in 2,000	≈ 1 in 26,000
Admixed American	~22k	1 in 340	≈ 1 in 22,000
African / African American	~21k	1 in 260	≈ 1 in 4,400
East Asian	~20k	1 in 140	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 440	none seen
Middle Eastern	~2,884	1 in 320	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓