ALS2

Chr 2AR

alsin Rho guanine nucleotide exchange factor ALS2

Also known as: ALS2CR6, ALSJ, IAHSP, PLSJ

The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

OMIMResearchGenerating clinical summary…
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 OE?0.39 (0.300.52)
00.351.4
Missense OE?0.82 (0.770.87)
00.61.4
Synonymous OE?0.97
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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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