ALS2 alsin Rho guanine nucleotide exchange factor ALS2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALS2provided by HGNC
Official Full Name: alsin Rho guanine nucleotide exchange factor ALS2provided by HGNC
Primary source: HGNC:HGNC:443
See related: Ensembl:ENSG00000003393 MIM:606352; AllianceGenome:HGNC:443
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ALSJ; PLSJ; IAHSP; ALS2CR6
Summary: 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]
Expression: Ubiquitous expression in heart (RPKM 4.3), brain (RPKM 3.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q33.1

Exon count:: 38

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (201700267..201780933, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (202180871..202263022, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (202564990..202645656, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The N-terminal intrinsically disordered region mediates intracellular localization and self-oligomerization of ALS2.
Title: The N-terminal intrinsically disordered region mediates intracellular localization and self-oligomerization of ALS2.
ALS2-related disorders in Spanish children.
Title: ALS2-related disorders in Spanish children.
Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations.
Title: Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations.
ALS2, the small GTPase Rab17-interacting protein, regulates maturation and sorting of Rab17-associated endosomes.
Title: ALS2, the small GTPase Rab17-interacting protein, regulates maturation and sorting of Rab17-associated endosomes.
These findings define a novel pathway whereby Alsin catalyzes the assembly of the Rab5 endocytic machinery on mitochondria. Defects in stress-sensing by endosomes could be crucial for mitochondrial quality control during the onset of amyotrophic lateral sclerosis.
Title: Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria.
Disorganized higher structures of ALS2 variants impaired endosomal localization and the stability, leading to loss of the ALS2 function.
Title: Altered oligomeric states in pathogenic ALS2 variants associated with juvenile motor neuron diseases cause loss of ALS2-mediated endosomal function.
This study identified a novel ALS2 pathogenic founder variant in Iran that further adds to the allelic heterogeneity of infantile-onset ascending hereditary spastic paralysis.
Title: Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.
Nonsense mutation in ALS2 gene is associated with severe and progressive infantile onset of spastic paralysis.
Title: A novel mutation in ALS2 associated with severe and progressive infantile onset of spastic paralysis.
We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family
Title: Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.
This study identified two novel ALS2 mutations in two Pakistani families with infantile-onset ascending hereditary spastic paraplegia cosegregating with the disease.
Title: Identification of two novel ALS2 mutations in infantile-onset ascending hereditary spastic paraplegia.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Amyotrophic lateral sclerosis type 2, juvenile MedGen: C1859807 OMIM: 205100 GeneReviews: ALS2-Related Disorder, Amyotrophic Lateral Sclerosis Overview	Compare labs
Infantile-onset ascending hereditary spastic paralysis MedGen: C2931441 OMIM: 607225 GeneReviews: ALS2-Related Disorder	Compare labs
Juvenile primary lateral sclerosis MedGen: C1853396 OMIM: 606353 GeneReviews: ALS2-Related Disorder	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G31879 (e-PCR)
- UniSTS:56579

SHGC-143239 (e-PCR)
- UniSTS:183311

RH12092 (e-PCR)
- UniSTS:26399

G54487 (e-PCR)
- UniSTS:140835

RH92914 (e-PCR)
- UniSTS:85364

D2S2309 (e-PCR)
- UniSTS:74872

ALS2__4284 (e-PCR)
- UniSTS:463537

SHGC-79895 (e-PCR)
- UniSTS:183476

G31881 (e-PCR)
- UniSTS:48895

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables small GTPase binding	IBA Inferred from Biological aspect of Ancestor more info
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed
enables small GTPase binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in behavioral fear response	IEA Inferred from Electronic Annotation more info
involved_in endosomal transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in endosome organization	NAS Non-traceable Author Statement more info	PubMed
involved_in locomotory behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lysosomal transport	IDA Inferred from Direct Assay more info	PubMed
involved_in neuromuscular junction development	IEA Inferred from Electronic Annotation more info
involved_in neuron projection morphogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of Rac protein signal transduction	IC Inferred by Curator more info	PubMed
involved_in positive regulation of protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein homooligomerization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization	IEA Inferred from Electronic Annotation more info
involved_in receptor recycling	IEA Inferred from Electronic Annotation more info
involved_in regulation of GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of endosome size	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission, glutamatergic	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in centrosome	IBA Inferred from Biological aspect of Ancestor more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in growth cone	ISS Inferred from Sequence or Structural Similarity more info
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in lamellipodium	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in ruffle	ISS Inferred from Sequence or Structural Similarity more info
located_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: alsin

Names: ALS2, alsin Rho guanine nucleotide exchange factor; amyotrophic lateral sclerosis 2 (juvenile); amyotrophic lateral sclerosis 2 chromosomal region candidate gene 6 protein; amyotrophic lateral sclerosis 2 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008775.1 RefSeqGene

Range

5240..85906

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_654

mRNA and Protein(s)

NM_001135745.2 → NP_001129217.1 alsin isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an internal polyA site resulting in a substantially shorter transcript with a unique 3' coding region, compared to variant 1. The encoded isoform (2), also known as the short form, is substantially shorter and has a unique C-terminus, compared to isoform 1.

Source sequence(s)

AB053306, AC007279, AK023024, BU623061

Consensus CDS

CCDS46492.1

UniProtKB/TrEMBL

A0A7P0TBB0

Related

ENSP00000429223.1, ENST00000467448.5

Conserved Domains (2) summary

pfam00415
Location:170 → 216

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat
NM_001410975.1 → NP_001397904.1 alsin isoform 3

Status: REVIEWED

Source sequence(s)

AC007242, AC007279

Consensus CDS

CCDS92925.1

UniProtKB/TrEMBL

A0A7P0T8F3

Related

ENSP00000505071.1, ENST00000681619.1
NM_020919.4 → NP_065970.2 alsin isoform 1

See identical proteins and their annotated locations for NP_065970.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1), also known as the LF or long form.

Source sequence(s)

AF391100, AK291029, BM978733

Consensus CDS

CCDS42800.1

UniProtKB/Swiss-Prot

Q53TT1, Q53TV2, Q8N1E0, Q96PC4, Q96Q41, Q96Q42, Q9H973, Q9HCK9

UniProtKB/TrEMBL

A0A2X0SFA0

Related

ENSP00000264276.6, ENST00000264276.11

Conserved Domains (8) summary

COG4642
Location:1049 → 1188

COG4642; Uncharacterized conserved protein [Function unknown]

cd13269
Location:905 → 1010

PH_alsin; Alsin Pleckstrin homology (PH) domain

pfam00169
Location:926 → 1004

PH; PH domain

pfam00415
Location:527 → 574

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam02204
Location:1554 → 1653

VPS9; Vacuolar sorting protein 9 (VPS9) domain

pfam02493
Location:1100 → 1120

MORN; MORN repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat

cl02571
Location:695 → 879

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

201700267..201780933 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006712654.4 → XP_006712717.1 alsin isoform X1

See identical proteins and their annotated locations for XP_006712717.1

UniProtKB/Swiss-Prot

Q53TT1, Q53TV2, Q8N1E0, Q96PC4, Q96Q41, Q96Q42, Q9H973, Q9HCK9

UniProtKB/TrEMBL

A0A2X0SFA0

Conserved Domains (8) summary

COG4642
Location:1049 → 1188

COG4642; Uncharacterized conserved protein [Function unknown]

cd13269
Location:905 → 1010

PH_alsin; Alsin Pleckstrin homology (PH) domain

pfam00169
Location:926 → 1004

PH; PH domain

pfam00415
Location:527 → 574

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam02204
Location:1554 → 1653

VPS9; Vacuolar sorting protein 9 (VPS9) domain

pfam02493
Location:1100 → 1120

MORN; MORN repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat

cl02571
Location:695 → 879

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
XM_047445224.1 → XP_047301180.1 alsin isoform X2
XM_006712655.4 → XP_006712718.1 alsin isoform X6

UniProtKB/TrEMBL

A0A7P0T993

Conserved Domains (6) summary

COG4642
Location:361 → 500

COG4642; Uncharacterized conserved protein [Function unknown]

cd13269
Location:217 → 322

PH_alsin; Alsin Pleckstrin homology (PH) domain

pfam00169
Location:238 → 316

PH; PH domain

pfam02204
Location:866 → 965

VPS9; Vacuolar sorting protein 9 (VPS9) domain

pfam02493
Location:412 → 432

MORN; MORN repeat

cl02571
Location:7 → 191

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
XM_017004572.3 → XP_016860061.1 alsin isoform X7

UniProtKB/TrEMBL

A0A7P0T993

Related

ENSP00000505568.1, ENST00000681558.1
XM_047445238.1 → XP_047301194.1 alsin isoform X4
XM_017004570.3 → XP_016860059.1 alsin isoform X3

UniProtKB/TrEMBL

A0A7P0T951

Related

ENSP00000505473.1, ENST00000680927.1

Conserved Domains (7) summary

COG4642
Location:1049 → 1188

COG4642; Uncharacterized conserved protein [Function unknown]

cd13269
Location:905 → 1010

PH_alsin; Alsin Pleckstrin homology (PH) domain

pfam00169
Location:926 → 1004

PH; PH domain

pfam00415
Location:527 → 574

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam02493
Location:1100 → 1120

MORN; MORN repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat

cl02571
Location:695 → 879

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
XM_047445241.1 → XP_047301197.1 alsin isoform X5

UniProtKB/TrEMBL

A0A7P0Z4I4

Related

ENSP00000506172.1, ENST00000679916.1