ARL3

ADP ribosylation factor like GTPase 3, the group of ARF GTPase family

Basic information

Region (hg38): 10:102673730-102714397

Links

ENSG00000138175 ∙ NCBI:403 ∙ OMIM:604695 ∙ HGNC:694 ∙ Uniprot:P36405 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 17 (Strong), mode of inheritance: AR
• retinitis pigmentosa 83 (Limited), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Joubert syndrome (Supportive), mode of inheritance: AR
• retinitis pigmentosa (Limited), mode of inheritance: AD
• retinitis pigmentosa 83 (Strong), mode of inheritance: AD
• Joubert syndrome 35 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 35; Retinitis pigmentosa 83	AR	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	Craniofacial; Neurologic; Ophthalmologic; Renal	26964041; 30269812
The condition may involve multi-systemic manifestations, including sequelae affecting the renal systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARL3 gene.

• not provided (110 variants)
• Inborn genetic diseases (7 variants)
• Joubert syndrome 35 (3 variants)
• Retinitis pigmentosa 83 (3 variants)
• Retinitis pigmentosa (2 variants)
• not specified (1 variants)
• Joubert syndrome 35;Retinitis pigmentosa 83 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARL3 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			1	20	1	22
missense	1		50	1		52
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			5			5
splice region			7	1		8
non coding				18	2	20
Total	1	0	61	39	3

Highest pathogenic variant AF is 0.0000131

Variants in ARL3

This is a list of pathogenic ClinVar variants found in the ARL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-102676908-C-G			Uncertain significance (Nov 12, 2022)
10-102676908-C-T			Uncertain significance (Feb 01, 2022)
10-102676921-G-A			Uncertain significance (Sep 27, 2022)
10-102676925-A-G			Uncertain significance (Jan 31, 2020)
10-102676931-T-A			Uncertain significance (Aug 13, 2022)
10-102676933-C-T			Uncertain significance (Jul 04, 2022)
10-102676934-A-G		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
10-102676935-T-C		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)
10-102676948-G-A			Likely benign (Oct 28, 2021)
10-102676954-T-G			Likely benign (Apr 10, 2021)
10-102676958-C-T			Likely benign (Jan 18, 2023)
10-102685805-T-C			Likely benign (Mar 28, 2022)
10-102685810-T-C			Uncertain significance (Jul 17, 2022)
10-102685815-C-A			Uncertain significance (Nov 10, 2022)
10-102685815-C-T			Uncertain significance (Oct 13, 2022)
10-102685821-C-T			Uncertain significance (Dec 06, 2023)
10-102685822-G-A			Likely benign (Nov 13, 2023)
10-102685824-C-T		Inborn genetic diseases	Uncertain significance (Dec 04, 2023)
10-102685835-A-C			Uncertain significance (Dec 18, 2022)
10-102685845-A-C		Joubert syndrome 35;Retinitis pigmentosa 83	Uncertain significance (May 22, 2023)
10-102685848-A-C			Uncertain significance (Mar 12, 2021)
10-102685865-C-T			Uncertain significance (Jun 04, 2022)
10-102685866-G-A			Uncertain significance (Feb 23, 2022)
10-102685869-C-T			Uncertain significance (Mar 18, 2023)
10-102685870-G-A		Retinal dystrophy	Benign/Likely benign (Oct 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARL3	protein_coding	protein_coding	ENST00000260746	6	40677

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00141	0.879	125736	0	8	125744	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.16	65	97.1	0.670	0.00000500	1193
Missense in Polyphen		19	43.385	0.43794		517
Synonymous	0.136	36	37.1	0.972	0.00000208	338
Loss of Function	1.35	6	10.8	0.556	5.42e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000531	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000662	0.0000653
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). Required for normal cytokinesis and cilia signaling. Requires assistance from GTPase- activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms. Required for targeting proteins such as NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium. Does not act as an allosteric activator of the cholera toxin catalytic subunit. {ECO:0000269|PubMed:16525022, ECO:0000269|PubMed:18588884, ECO:0000269|PubMed:22085962}.
• Pathway: Trafficking of myristoylated proteins to the cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.357
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.54

Haploinsufficiency Scores

• pHI: 0.528
• hipred: Y
• hipred_score: 0.710
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arl3
• Phenotype: endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: mitotic cytokinesis;kidney development;post-Golgi vesicle-mediated transport;Golgi to plasma membrane transport;smoothened signaling pathway;small GTPase mediated signal transduction;intraciliary transport;photoreceptor cell development;cilium assembly;protein localization to ciliary membrane
• Cellular component: Golgi membrane;nucleus;Golgi apparatus;centrosome;spindle microtubule;cytoplasmic microtubule;cilium;microtubule cytoskeleton;midbody;photoreceptor connecting cilium;extracellular exosome
• Molecular function: magnesium ion binding;GTPase activity;protein binding;GTP binding;microtubule binding;GDP binding;GTPase activating protein binding