ARL13B

ADP ribosylation factor like GTPase 13B, the group of ARF GTPase family

Basic information

Region (hg38): 3:93980138-94055678

Previous symbols: [ "ARL2L1" ]

Links

ENSG00000169379 ∙ NCBI:200894 ∙ OMIM:608922 ∙ HGNC:25419 ∙ Uniprot:Q3SXY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 8 (Strong), mode of inheritance: AR
• Joubert syndrome 8 (Moderate), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome 8 (Definitive), mode of inheritance: AR
• Joubert syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 8	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	Neurologic; Ophthalmologic; Renal	18674751; 20615230; 22241855; 25138100
The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic 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 ARL13B gene.

• Joubert syndrome 8 (253 variants)
• not provided (44 variants)
• Inborn genetic diseases (28 variants)
• not specified (15 variants)
• Joubert syndrome and related disorders (8 variants)
• Joubert syndrome 1 (3 variants)
• Familial aplasia of the vermis (2 variants)
• Long QT syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARL13B 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	35		36
missense	2	3	117	3	3	128
nonsense	4	1				5
start loss						0
frameshift	7	3				10
inframe indel			5			5
splice donor/acceptor (+/-2bp)		4	2			6
splice region			6	19		25
non coding			17	49	10	76
Total	13	11	142	87	13

Highest pathogenic variant AF is 0.0000132

Variants in ARL13B

This is a list of pathogenic ClinVar variants found in the ARL13B region.

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

Position	Type	Phenotype	Significance	ClinVar
3-93980161-C-T			Likely benign (Jun 19, 2018)
3-93980190-G-T			Benign (Aug 25, 2018)
3-93980374-C-A		not specified	Likely benign (Oct 27, 2017)
3-93980428-T-G		Joubert syndrome 8	Conflicting classifications of pathogenicity (Jul 16, 2023)
3-93980429-C-T		Joubert syndrome 8	Likely benign (Aug 04, 2023)
3-93980435-G-C		Joubert syndrome 8	Likely benign (Feb 19, 2022)
3-93980436-A-T			Uncertain significance (May 23, 2018)
3-93980441-C-T		Joubert syndrome 8	Likely benign (Aug 10, 2023)
3-93980443-G-A		Joubert syndrome 8	Uncertain significance (Jul 11, 2022)
3-93980445-T-G		Joubert syndrome 8	Uncertain significance (Aug 24, 2021)
3-93980453-C-T		Joubert syndrome 8 • ARL13B-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2023)
3-93980464-G-A		Joubert syndrome 8	Uncertain significance (Jul 12, 2022)
3-93980478-G-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
3-93980480-C-A		Joubert syndrome 8	Likely benign (Jun 29, 2021)
3-93980483-G-A		Joubert syndrome and related disorders	Likely pathogenic (Feb 07, 2023)
3-93980490-G-A		Joubert syndrome 8 • ARL13B-related disorder	Likely benign (Nov 28, 2023)
3-93980495-CA-C		Joubert syndrome 8	Likely benign (Jan 04, 2023)
3-93980496-A-G		Joubert syndrome 8	Likely benign (Jun 30, 2023)
3-93980497-G-A		Joubert syndrome 8	Likely benign (Feb 08, 2022)
3-93980498-C-G		Joubert syndrome 8	Uncertain significance (Feb 16, 2022)
3-93980500-G-C		Joubert syndrome 8	Likely benign (Mar 07, 2021)
3-93980502-C-G		Joubert syndrome 8	Likely benign (Nov 01, 2022)
3-93980502-C-T		Joubert syndrome 8	Benign (Apr 22, 2022)
3-93980726-AGT-A			Benign (Oct 21, 2019)
3-93980726-AGTGT-A			Benign (Oct 18, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARL13B	protein_coding	protein_coding	ENST00000394222	10	75530

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-9	0.719	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0592	230	227	1.01	0.0000113	2794
Missense in Polyphen		59	62.602	0.94246		746
Synonymous	-0.270	81	78.0	1.04	0.00000375	778
Loss of Function	1.42	17	24.6	0.691	0.00000122	308

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000415	0.000414
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000329	0.000326
Finnish	0.000232	0.000231
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.000329	0.000326
South Asian	0.000231	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure. May act by maintaining the association between IFT subcomplexes A and B. Binds GTP but is not able to hydrolyze it; the GTPase activity remains unclear. Required to pattern the neural tube. Involved in cerebral cortex development: required for the initial formation of a polarized radial glial scaffold, the first step in the construction of the cerebral cortex, by regulating ciliary signaling. Regulates the migration and placement of postmitotic interneurons in the developing cerebral cortex. May regulate endocytic recycling traffic; however, additional evidences are required to confirm these data. {ECO:0000269|PubMed:23150559}.
• Disease: DISEASE: Joubert syndrome 8 (JBTS8) [MIM:612291]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:18674751, ECO:0000269|PubMed:25138100}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ARL13B-mediated ciliary trafficking of INPP5E;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0996

Intolerance Scores

• loftool: 0.934
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.22

Haploinsufficiency Scores

• pHI: 0.0672
• hipred: N
• hipred_score: 0.231
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arl13b
• 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; embryo phenotype; respiratory system 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; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: arl13b
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: heart looping;smoothened signaling pathway;dorsal/ventral pattern formation;response to lithium ion;neural tube patterning;interneuron migration from the subpallium to the cortex;formation of radial glial scaffolds;cilium assembly;left/right axis specification;receptor localization to non-motile cilium;non-motile cilium assembly
• Cellular component: cilium;axoneme;motile cilium;ciliary membrane;non-motile cilium
• Molecular function: protein binding;GTP binding