ALS2CL

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

Basic information

Region (hg38): 3:46668994-46693704

Links

ENSG00000178038 ∙ NCBI:259173 ∙ OMIM:612402 ∙ HGNC:20605 ∙ Uniprot:Q60I27 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schizophrenia	AD	General	Evidence or clinical applicability is unclear	Neurologic	21743468; 23425335

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALS2CL gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALS2CL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			59	4		63
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	60	4	0

Variants in ALS2CL

This is a list of pathogenic ClinVar variants found in the ALS2CL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-46670994-T-A		not specified	Uncertain significance (Dec 08, 2023)
3-46671024-T-C		not specified	Uncertain significance (Mar 03, 2022)
3-46671542-C-G		not specified	Uncertain significance (Jan 11, 2023)
3-46671891-G-A		not specified	Uncertain significance (Jul 09, 2021)
3-46671984-C-T		not specified	Uncertain significance (Jan 24, 2023)
3-46671984-CG-C		not specified	Uncertain significance (Mar 29, 2016)
3-46672028-G-A		not specified	Uncertain significance (Feb 28, 2024)
3-46672031-G-A		not specified	Uncertain significance (Apr 16, 2024)
3-46672143-A-T		not specified	Uncertain significance (Sep 16, 2021)
3-46672180-T-C		not specified	Uncertain significance (Apr 17, 2024)
3-46674704-A-T		not specified	Uncertain significance (Dec 02, 2021)
3-46675627-G-C		not specified	Uncertain significance (May 28, 2024)
3-46675660-C-T		not specified	Uncertain significance (Apr 18, 2023)
3-46675661-G-A		not specified	Uncertain significance (Mar 01, 2023)
3-46675675-C-T		not specified	Likely benign (Nov 18, 2023)
3-46676294-C-T		not specified	Uncertain significance (Mar 11, 2022)
3-46676300-C-T		not specified	Uncertain significance (Feb 23, 2023)
3-46676321-C-T		not specified	Uncertain significance (Dec 05, 2022)
3-46676362-C-T		not specified	Uncertain significance (Nov 30, 2022)
3-46676667-T-C		not specified	Uncertain significance (Dec 21, 2023)
3-46676671-G-A		not specified	Uncertain significance (May 20, 2024)
3-46676707-C-T		not specified	Uncertain significance (Feb 10, 2023)
3-46676725-C-T		not specified	Uncertain significance (Jun 03, 2022)
3-46676873-G-A		not specified	Uncertain significance (Jan 09, 2024)
3-46676886-C-T		not specified	Uncertain significance (Nov 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALS2CL	protein_coding	protein_coding	ENST00000318962	25	24708

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.30e-28	0.00357	125023	4	720	125747	0.00288

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.169	553	564	0.980	0.0000354	6110
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00256	0.00255
Ashkenazi Jewish	0.00120	0.00119
East Asian	0.00305	0.00305
Finnish	0.00495	0.00491
European (Non-Finnish)	0.00285	0.00276
Middle Eastern	0.00305	0.00305
South Asian	0.00431	0.00429
Other	0.00425	0.00424

dbNSFP

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}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.956
• rvis_EVS: -0.92
• rvis_percentile_EVS: 9.81

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.377
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.654

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Als2cl

Gene ontology

• Biological process: endosome organization;positive regulation of GTPase activity
• Cellular component: cytosol
• Molecular function: GTPase activator activity;Rab guanyl-nucleotide exchange factor activity;identical protein binding