ALS2CL

protein-coding

ALS2 C-terminal like, the group of VPS9 domain containing|Dbl family Rho GEFs

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in endosomal transport. Predicted to act upstream of or within intracellular protein localization. Predicted to be located in cytosol. Predicted to be active in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_147129.5

Inheritance

ClinVar variants

U:158B:21

Top phenotype

Schizophrenia

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr3:46,668,995-46,693,704

External References & Databases

Ensembl (ENSG00000178038)

Transcript & Mutation Effects

hg38 • Region Span ~24.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

SchizophreniaAD

Manifestation: Neurologic

Intervention: General

Rationale: Evidence or clinical applicability is unclear

Refs: 21743468; 23425335

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALS2CL variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 176

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_147129.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	9 clinvar		11
missense			150 clinvar	11 clinvar		161
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	158	21	0	179

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 77 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_147129.5	RefSeq	NP_667340.2	25	MANE Select
ENST00000318962.9	Ensembl	ENSP00000313670.4	25	MANE Select
NM_001190707.2	RefSeq	NP_001177636.1	25	Standard
ENST00000415953.5	Ensembl	ENSP00000413223.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Rab regulation of trafficking
RAB GEFs exchange GTP for GDP on RABs

Biological Process

endosome organization
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
Rab guanyl-nucleotide exchange factor activity
identical protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318962
Coding exons: 25
Length: 24708
Individuals with no LoFs: 125023
Homozygous LoFs: 4
Heterozygous LoFs: 720
Defined: 125747
p: 0.00288

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.169	553	564	0.980	0.0000354	6110
Missense (PolyPhen)		152	178.1	0.85344		2030
Synonymous	0.649	241	254	0.948	0.0000167	1922
Loss of Function	1.04	47	55.4	0.849	0.00000271	597

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.0021	0.0021	notable
Ashkenazi Jewish	0.0012	0.0012	notable
East Asian	0.0030	0.0030	notable
Finnish	0.0049	0.0049	notable
European (Non-Finnish)	0.0028	0.0028	notable
South Asian	0.0043	0.0043	notable
Other	0.0043	0.0042	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) for Rab5 GTPase. Regulates the ALS2-mediated endosome dynamics. {ECO:0000269|PubMed:15388334, ECO:0000269|PubMed:16473597, ECO:0000269|PubMed:17239822}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.956
RVIS EVS: -0.92
RVIS percentile EVS: 9.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.654

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High