ARL2

ADP ribosylation factor like GTPase 2, the group of ARF GTPase family|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:65014160-65022184

Links

ENSG00000213465 ∙ NCBI:402 ∙ OMIM:601175 ∙ HGNC:693 ∙ Uniprot:P36404 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	30945270

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARL2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARL2 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			9	2		11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	2	0

Variants in ARL2

This is a list of pathogenic ClinVar variants found in the ARL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-65014236-T-C		not specified	Uncertain significance (Dec 15, 2023)
11-65014251-G-T		Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1	Pathogenic (Oct 13, 2021)
11-65018416-G-A		not specified	Uncertain significance (Oct 05, 2023)
11-65018422-G-A		not specified	Uncertain significance (Feb 06, 2023)
11-65018426-C-G		not specified	Uncertain significance (Sep 26, 2024)
11-65018615-G-A		not specified	Uncertain significance (Dec 14, 2022)
11-65018681-G-A		not specified	Likely benign (Nov 18, 2022)
11-65018710-C-A		not specified	Uncertain significance (Jan 23, 2024)
11-65020495-G-A		not specified	Uncertain significance (Oct 27, 2022)
11-65020496-C-T		ARL2-related condition	Likely benign (May 03, 2024)
11-65020498-A-T		not specified	Uncertain significance (Jun 22, 2021)
11-65021742-C-T		not specified	Uncertain significance (Feb 15, 2023)
11-65021743-G-A		not specified	Uncertain significance (Jan 31, 2022)
11-65021778-G-A		not specified	Uncertain significance (May 21, 2024)
11-65021793-C-G		not specified	Uncertain significance (Oct 01, 2024)
11-65021800-C-T		not specified	Likely benign (Aug 16, 2022)
11-65021824-A-G		not specified	Uncertain significance (Sep 10, 2024)
11-65021835-C-T		not specified	Uncertain significance (Nov 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARL2	protein_coding	protein_coding	ENST00000246747	5	8072

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0214	0.914	125686	0	8	125694	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	82	113	0.723	0.00000722	1176
Missense in Polyphen		22	42.918	0.51261		507
Synonymous	-0.422	50	46.3	1.08	0.00000285	363
Loss of Function	1.58	4	9.15	0.437	4.75e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000634	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000273	0.0000264
Middle Eastern	0.000163	0.000163
South Asian	0.0000335	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle. {ECO:0000269|PubMed:10831612, ECO:0000269|PubMed:16525022, ECO:0000269|PubMed:18234692, ECO:0000269|PubMed:18588884, ECO:0000269|PubMed:20740604}.
• Pathway: Metabolism of proteins;Metabolism;Regulation of insulin secretion;Protein folding;Post-chaperonin tubulin folding pathway;Integration of energy metabolism (Consensus)

Intolerance Scores

• loftool: 0.423
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.12

Haploinsufficiency Scores

• pHI: 0.333
• hipred: N
• hipred_score: 0.213
• ghis: 0.510

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.926

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arl2

Gene ontology

• Biological process: tubulin complex assembly;centrosome cycle;positive regulation of cell-substrate adhesion;regulation of microtubule polymerization;positive regulation of microtubule polymerization;negative regulation of GTPase activity;regulation of insulin secretion;maintenance of protein location in nucleus;bicellular tight junction assembly
• Cellular component: nucleus;nucleolus;mitochondrial intermembrane space;mitochondrial matrix;Golgi apparatus;centrosome;cytosol;focal adhesion;cilium;lateral plasma membrane
• Molecular function: GTPase activity;GTPase inhibitor activity;protein binding;GTP binding