ALS2

Chr 2AR

alsin Rho guanine nucleotide exchange factor ALS2

Also known as: ALS2CR6, ALSJ, IAHSP, PLSJ

The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5, localizing to early endosomal compartments where it modulates endosomal dynamics. Mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis, juvenile primary lateral sclerosis, and infantile-onset ascending spastic paralysis. The pathogenic mechanism involves disruption of endosomal trafficking through impaired RAB5 activation.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismARLOEUF 0.524 OMIM phenotypes
Clinical SummaryALS2
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Gene-Disease Validity (ClinGen)
ALS2-related motor neuron disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.000
Z-score 5.42
OE 0.39 (0.300.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.90Z-score
OE missense 0.82 (0.770.87)
713 obs / 870.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.300.52)
00.351.4
Missense OE0.82 (0.770.87)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 36 / 92.2Missense obs/exp: 713 / 870.5Syn Z: 0.48

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALS2 · 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

No active trials found for this gene.

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Clinical Literature
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