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
microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1 (Strong), 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.

not_specified (24 variants)
ARL2-related_condition (1 variants)
Microcornea,_rod-cone_dystrophy,_cataract,_and_posterior_staphyloma_1 (1 variants)

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. These statistics are base on transcript: NM_000001667.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense	1 clinvar		22 clinvar	2 clinvar		25
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	22	3	0

Highest pathogenic variant AF is 0.0000323865

Loading clinvar variants...

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
Phenotype

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