ARL13B

Summary

ARL13B (ARF like GTPase 13B, HGNC:25419) is a protein-coding gene on chromosome 3q11.1-q11.2, encoding ADP-ribosylation factor-like protein 13B (Q3SXY8). Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure.

This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia. Mutations in this gene are the cause of Joubert syndrome 8. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 200894 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 475 total — 17 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 51
• MANE Select transcript: NM_001174150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25419
Approved symbol	ARL13B
Name	ARF like GTPase 13B
Location	3q11.1-q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761H079, JBTS8
Ensembl gene	ENSG00000169379
Ensembl biotype	protein_coding
OMIM	608922
Entrez	200894

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 13 protein_coding, 9 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000303097, ENST00000335438, ENST00000394222, ENST00000460371, ENST00000471138, ENST00000475206, ENST00000478400, ENST00000486562, ENST00000492165, ENST00000535334, ENST00000679404, ENST00000679587, ENST00000679601, ENST00000679607, ENST00000679654, ENST00000679657, ENST00000679666, ENST00000679739, ENST00000679872, ENST00000680414, ENST00000680430, ENST00000680994, ENST00000681013, ENST00000681247, ENST00000681377, ENST00000681380, ENST00000681655

RefSeq mRNA: 6 — MANE Select: NM_001174150 NM_001174150, NM_001174151, NM_001321328, NM_001410782, NM_144996, NM_182896

CCDS: CCDS2924, CCDS2925, CCDS54615, CCDS93326

Canonical transcript exons

ENST00000394222 — 10 exons

Exon	Start	End
ENSE00001727293	94053187	94055678
ENSE00003475004	94036552	94036754
ENSE00003508428	93980155	93980482
ENSE00003541567	94050824	94050892
ENSE00003555667	93995874	93995944
ENSE00003562804	94039880	94039988
ENSE00003585388	94003659	94003908
ENSE00003612905	94043015	94043240
ENSE00003633998	94049406	94049522
ENSE00003678021	94035331	94035436

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 93.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8729 / max 301.6817, expressed in 1768 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37472	10.7461	1767
37473	0.1267	41

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.27	gold quality
calcaneal tendon	UBERON:0003701	90.65	gold quality
bronchial epithelial cell	CL:0002328	89.34	gold quality
sural nerve	UBERON:0015488	88.65	gold quality
bronchus	UBERON:0002185	88.46	gold quality
oocyte	CL:0000023	86.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.59	gold quality
ventricular zone	UBERON:0003053	85.53	gold quality
cartilage tissue	UBERON:0002418	84.33	gold quality
cauda epididymis	UBERON:0004360	83.70	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.48	gold quality
lower lobe of lung	UBERON:0008949	82.09	gold quality
caput epididymis	UBERON:0004358	81.05	gold quality
ganglionic eminence	UBERON:0004023	80.93	gold quality
skin of hip	UBERON:0001554	80.87	gold quality
smooth muscle tissue	UBERON:0001135	80.30	gold quality
islet of Langerhans	UBERON:0000006	79.10	gold quality
gall bladder	UBERON:0002110	79.03	gold quality
lung	UBERON:0002048	78.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.97	gold quality
stromal cell of endometrium	CL:0002255	78.80	gold quality
tibial nerve	UBERON:0001323	78.44	gold quality
popliteal artery	UBERON:0002250	78.21	gold quality
tibial artery	UBERON:0007610	78.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.17	gold quality
artery	UBERON:0001637	77.85	gold quality
aorta	UBERON:0000947	77.43	gold quality
tibia	UBERON:0000979	77.28	gold quality
cortical plate	UBERON:0005343	77.07	gold quality
myometrium	UBERON:0001296	76.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

149 targeting ARL13B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 28)

• These findings suggest that N and C domains of Arl13b cooperatively regulate its ciliary localization and that N domain-dependent self-association of Arl13b may be important for its function in cilia biogenesis. (PMID:18554500)
• ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs (PMID:18674751)
• data implicate a role for JS-associated Arl13b at ciliary membranes, where it regulates ciliary transmembrane protein localizations and anterograde IFT assembly stability (PMID:20231383)
• data reveal a novel but conserved role for the SUMOylation modification of ciliary small GTPase ARL13B in specifically regulating the proper ciliary targeting of various sensory receptors (PMID:23128241)
• findings indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network that is involved in JBTS and NPHP but independent of the ones previously defined by NPHP and MKS proteins (PMID:23150559)
• Expression of Arl13b variants known to cause Joubert syndrome induce defective interneuronal migration, suggesting that defects in cilia-dependent interneuron migration may in part underlie the neurological defects in Joubert syndrome patients. (PMID:23153492)
• These results indicate a previously unidentified role for Arl13b in endocytic recycling traffic and suggest a link between Arl13b function and the actin cytoskeleton. (PMID:23223633)
• Arl13b acts as the all-rounder in cilia formation and signaling (Review). (PMID:23548655)
• X-ray crystallography of Arl13B demonstrates involvement of mutations R79Q and R200C in stabilizing intramolecular interactions. (PMID:24168557)
• We conclude that MKS/NPHP modules comprise a TZ barrier to ARL-13 diffusion, whereas IFT genes predominantly facilitate ARL-13 ciliary entry and/or retention via active transport mechanisms. (PMID:24339792)
• Thus our data identify a novel ARL13B variant that causes JS and retinopathy and suggest an extension of the phenotypic spectrum of ARL13B mutations to obesity. (PMID:25138100)
• ARL13B regulates IFT-A-mediated retrograde protein trafficking within cilia through its interaction with INPP5E. (PMID:27927754)
• Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria. (PMID:28158906)
• Biochemical characterization of purified mammalian ARL13B protein indicates that it is an atypical GTPase and ARL3 guanine nucleotide exchange factor (GEF).( (PMID:28487361)
• Our results show how Arl13b participates in Hedgehog pathway activation in gastric cancer (PMID:28611043)
• the results show that palmitoylation plays a unique and critical role in controlling the localization, stability, abundance, and thus function of ARL13b. Pharmacological manipulation of protein palmitoylation may be a strategy to alter cilia function. (PMID:28848045)
• A novel homozygous loss of function mutation in ARL13B was identified in patients with Joubert syndrome (PMID:29255182)
• High Arl13b expression is associated with medulloblastoma formation. (PMID:29378965)
• Authors propose a so far unknown function of ARL13B in anchoring ciliary membrane proteins to the axoneme through the direct interaction of its G-domain with tubulin. (PMID:29592971)
• Joubert syndrome protein ARL13B controls axoneme polyglutamylation. (PMID:30120249)
• Formation of primary cilia is downregulated in TULP3-knockout (KO) RPE1 cells. ARL13B and INPP5E fail to localize to primary cilia in TULP3-KO cells. (PMID:30583862)
• RAB family small GTP binding protein RAB 23 (Rab23) and ADP-ribosylation factor-like 13B (Arl13b) have been implicated in ciliopathy-associated human diseases and could regulate hedgehog proteins (Hh) signalling cascade in multifaceted manners [Review]. (PMID:31465935)
• Interaction of INPP5E with ARL13B is essential for its ciliary membrane retention but dispensable for its ciliary entry. (PMID:33372066)
• ARL3 activation requires the co-GEF BART and effector-mediated turnover. (PMID:33438581)
• TMEM67 is required for the gating function of the transition zone that controls entry of membrane-associated proteins ARL13B and INPP5E into primary cilia. (PMID:36334440)
• Rab8 and TNPO1 are ciliary transport adaptors for GTPase Arl13b by interacting with its RVEP motif containing ciliary targeting sequence. (PMID:36907439)
• Increasing Ciliary ARL13B Expression Drives Active and Inhibitor-Resistant Smoothened and GLI into Glioma Primary Cilia. (PMID:37830570)
• Novel compound heterozygous variants in ARL13B lead to Joubert syndrome. (PMID:38219074)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arl13b	ENSDARG00000012763
mus_musculus	Arl13b	ENSMUSG00000022911
rattus_norvegicus	Arl13b	ENSRNOG00000047194

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

ADP-ribosylation factor-like protein 13B — Q3SXY8 (reviewed: Q3SXY8)

Alternative names: ADP-ribosylation factor-like protein 2-like 1

All UniProt accessions (17): A0A7P0T892, A0A7P0T8G9, A0A7P0T8M9, A0A7P0T933, A0A7P0T969, A0A7P0T9A8, A0A7P0T9C1, A0A7P0TAL8, A0A7P0TAS1, A0A7P0Z407, A0A7P0Z473, A0A7P0Z4M2, A0A7P0Z4S0, B4DRI8, Q3SXY8, F8W837, F8WAY0

UniProt curated annotations — full annotation on UniProt →

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 fit; 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. Plays a role in ciliar trafficking of phosphatidylinositol phosphatase INPP5E in ciliogenesis. May regulate ARF6- and RAB22A-dependent endocytic recycling traffic.

Subunit / interactions. Monomer. Interacts with CIMAP3. Interacts with IFT complex B components IFT46 and IFT74. Interacts with EXOC2; regulates ARL13B localization to the cilium membrane. Interacts with actin; the interaction mediates colocalization of ARL13B and microtubules.

Subcellular location. Cell projection. Cilium membrane. Cilium. Cell membrane. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in the developing brain.

Post-translational modifications. Sumoylation is required for PKD2 entry into cilium.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal domain is required for localization to microtubules and the cell membrane.

Miscellaneous. Used as a ciliary marker because of its specific localization to microtubule doublets of the ciliary axoneme.

Similarity. Belongs to the small GTPase superfamily. Arf family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q3SXY8-1	1	yes
Q3SXY8-2	2
Q3SXY8-3	3

RefSeq proteins (6): NP_001167621, NP_001167622, NP_001308257, NP_001397711, NP_659433, NP_878899 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR051995	Ciliary_GTPase	Family

Pfam: PF00025

UniProt features (34 total): mutagenesis site 8, sequence variant 7, compositionally biased region 6, binding site 3, region of interest 2, lipid moiety-binding region 2, splice variant 2, chain 1, cross-link 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3SXY8-F1	72.92	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 28–35; 71–75; 130–133

Post-translational modifications (3): 8, 9, 329

Mutagenesis-validated functional residues (8):

Position	Phenotype
35	does not affect localization to cilia.
130	does not affect localization to cilia.
231	no effect. abolishes sumoylation; when associated with r-270; r-275; r-276; r-279 and r-329.
270	no effect. abolishes sumoylation; when associated with r-231; r-275; r-276; r-279 and r-329.
275	no effect. abolishes sumoylation; when associated with r-231; r-270; r-276; r-279 and r-329.
276	no effect. abolishes sumoylation; when associated with r-231; r-270; r-275; r-279 and r-329.
279	no effect. abolishes sumoylation; when associated with r-231; r-270; r-275; r-276 and r-329.
329	abolishes sumoylation. abolishes sumoylation; when associated with r-231; r-270; r-275; r-276 and r-279.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-5624958	ARL13B-mediated ciliary trafficking of INPP5E
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9615710	Late endosomal microautophagy
R-HSA-9646399	Aggrephagy
R-HSA-162582	Signal Transduction
R-HSA-1632852	Macroautophagy
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane
R-HSA-9012999	RHO GTPase cycle
R-HSA-9612973	Autophagy
R-HSA-9663891	Selective autophagy
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 296 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_CELL_MIGRATION, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, GOBP_SUBSTRATE_INDEPENDENT_TELENCEPHALIC_TANGENTIAL_MIGRATION

GO Biological Process (11): heart looping (GO:0001947), smoothened signaling pathway (GO:0007224), dorsal/ventral pattern formation (GO:0009953), neural tube patterning (GO:0021532), interneuron migration from the subpallium to the cortex (GO:0021830), formation of radial glial scaffolds (GO:0021943), cilium assembly (GO:0060271), left/right axis specification (GO:0070986), receptor localization to non-motile cilium (GO:0097500), non-motile cilium assembly (GO:1905515), determination of left/right symmetry (GO:0007368)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (19): acrosomal vesicle (GO:0001669), cytosol (GO:0005829), cilium (GO:0005929), axoneme (GO:0005930), microtubule cytoskeleton (GO:0015630), motile cilium (GO:0031514), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), intercellular bridge (GO:0045171), ciliary membrane (GO:0060170), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), non-motile cilium (GO:0097730), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Autophagy	3
RHO GTPase cycle	2
Cargo trafficking to the periciliary membrane	1
Selective autophagy	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1
Signaling by Rho GTPases	1
Macroautophagy	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	10
cilium	5
sperm flagellum	3
regionalization	2
left/right pattern formation	2
cytoskeleton	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
cell surface receptor signaling pathway	1
neural tube development	1
substrate-independent telencephalic tangential interneuron migration	1
cell morphogenesis	1
hindbrain radial glia guided cell migration	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
axis specification	1
protein localization to non-motile cilium	1
protein localization to ciliary membrane	1
cilium assembly	1
determination of bilateral symmetry	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
secretory granule	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule	1
ciliary plasm	1
microtubule organizing center	1

Protein interactions and networks

STRING

1756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL13B	CC2D2A	Q9P2K1	933
ARL13B	IFT88	Q13099	922
ARL13B	TMEM216	Q9P0N5	914
ARL13B	AHI1	Q8N157	910
ARL13B	TMEM67	Q5HYA8	902
ARL13B	RPGRIP1L	Q68CZ1	899
ARL13B	CEP290	O15078	884
ARL13B	NPHP1	O15259	872
ARL13B	OFD1	O75665	857
ARL13B	CEP164	Q9UPV0	824
ARL13B	PDE6D	O43924	789
ARL13B	KIF3A	Q9Y496	773
ARL13B	SHH	Q15465	753
ARL13B	SMO	Q99835	750
ARL13B	GPR161	Q8N6U8	733

IntAct

420 interactions, top by confidence:

A	B	Type	Score
EBP	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
SLC39A2	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
CD151	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
PLN	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
MAL2	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	STK25	psi-mi:“MI:0914”(association)	0.530
MINDY2	SLC27A2	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
RAB9A	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
VAMP2	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
CLEC7A	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
SMAGP	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
SLC35B1	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
FAXDC2	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
TMEM254	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
ANKRD46	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
KLRG1	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
PRB1	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
TMEM79	ARL13B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (382): ARL13B (Reconstituted Complex), ARL13B (Biochemical Activity), ARL13B (Affinity Capture-MS), ARL13B (Affinity Capture-MS), TTC30A (Affinity Capture-MS), STK25 (Affinity Capture-MS), TTC26 (Affinity Capture-MS), VAC14 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), TTI1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), IFT74 (Affinity Capture-MS), IFT52 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q1LSX9, A2APV2, A4IHK8, A8K855, A9JRL3, D3Z8X7, O00418, O08796, O35099, O60308, P55265, P70531, Q13905, Q1LX49, Q28CB1, Q3SXY8, Q3UFM5, Q4V8B2, Q5E9V1, Q5QNQ6, Q5R6Y9, Q5R9G1, Q5RHX6, Q62172, Q62796, Q640N2, Q66JG9, Q6DD21, Q6DFA1, Q6ZPF4, Q7Z699, Q7ZYB4, Q80V31, Q80V94, Q8CI95, Q8IVF7, Q8IWE4, Q8K0Q5, Q8K0V2, Q8K4M9

Diamond homologs: A8INQ0, A8ISN6, B5FYQ0, O04266, O04834, O08697, O23778, O45379, O48649, O48920, P0CM16, P0CM17, P0DH91, P11076, P19146, P20606, P22274, P26990, P26991, P36397, P36404, P36405, P36579, P37996, P38116, P40616, P40940, P40945, P40946, P49076, P51643, P51645, P51821, P51822, P51823, P51824, P61204, P61205, P61206, P61207

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
trans-Golgi Network Vesicle Budding	5	17.9×	3e-03
Golgi Associated Vesicle Biogenesis	5	14.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	6	32.5×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

475 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	19
Uncertain significance	217
Likely benign	157
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076313	NM_001174150.2(ARL13B):c.986dup (p.Asn330fs)	Pathogenic
1370150	NM_001174150.2(ARL13B):c.440dup (p.Ser148fs)	Pathogenic
1418737	NM_001174150.2(ARL13B):c.554G>A (p.Trp185Ter)	Pathogenic
1440955	NM_001174150.2(ARL13B):c.772C>T (p.Gln258Ter)	Pathogenic
1457416	NC_000003.11:g.(?93593089)(93845334_?)del	Pathogenic
1896131	NM_001174150.2(ARL13B):c.830del (p.Asn277fs)	Pathogenic
1991	NM_001174150.2(ARL13B):c.236G>A (p.Arg79Gln)	Pathogenic
1992	NM_001174150.2(ARL13B):c.246G>A (p.Trp82Ter)	Pathogenic
2035764	NM_001174150.2(ARL13B):c.538A>T (p.Lys180Ter)	Pathogenic
2203408	NM_001174150.2(ARL13B):c.223G>A (p.Gly75Arg)	Pathogenic
2288477	NM_001174150.2(ARL13B):c.274dup (p.Val92fs)	Pathogenic
2427601	NC_000003.11:g.(?93714775)(93724716_?)del	Pathogenic
3013775	NM_001174150.2(ARL13B):c.709C>T (p.Gln237Ter)	Pathogenic
3246903	NC_000003.11:g.(?93754155)(93755618_?)del	Pathogenic
3672046	NM_001174150.2(ARL13B):c.679C>T (p.Arg227Ter)	Pathogenic
4716798	NM_001174150.2(ARL13B):c.977del (p.Gln326fs)	Pathogenic
4764779	NM_001174150.2(ARL13B):c.822_823del (p.Asn277fs)	Pathogenic
1068135	NM_001174150.2(ARL13B):c.689+2T>G	Likely pathogenic
1704628	NC_000003.11:g.93714775_(93722753_93754174)del	Likely pathogenic
1722485	NM_001174150.2(ARL13B):c.801del (p.Asn267fs)	Likely pathogenic
1723383	NM_001174150.2(ARL13B):c.246del (p.Ile81_Trp82insTer)	Likely pathogenic
1808663	GRCh37/hg19 3q11.1-11.2(chr3:93519465-94372131)x1	Likely pathogenic
191177	NM_001174150.2(ARL13B):c.765T>A (p.Asn255Lys)	Likely pathogenic
2053319	NM_001174150.2(ARL13B):c.1141+1G>A	Likely pathogenic
2445749	NM_001174150.2(ARL13B):c.59+1G>A	Likely pathogenic
2501016	NM_001174150.2(ARL13B):c.976C>T (p.Gln326Ter)	Likely pathogenic
3589653	NM_001174150.2(ARL13B):c.51del (p.Glu17fs)	Likely pathogenic
3589657	NM_001174150.2(ARL13B):c.381-1G>A	Likely pathogenic
3589658	NM_001174150.2(ARL13B):c.402_405del (p.Gly136fs)	Likely pathogenic
3589662	NM_001174150.2(ARL13B):c.664C>T (p.Arg222Ter)	Likely pathogenic

SpliceAI

2392 predictions. Top by Δscore:

Variant	Effect	Δscore
3:94003654:A:AG	acceptor_gain	1.0000
3:94003655:A:G	acceptor_gain	1.0000
3:94003856:GC:G	donor_gain	1.0000
3:94003871:C:G	donor_gain	1.0000
3:94003894:A:T	donor_gain	1.0000
3:94003907:GT:G	donor_gain	1.0000
3:94003909:G:GG	donor_gain	1.0000
3:94035433:GATA:G	donor_gain	1.0000
3:94035434:ATA:A	donor_gain	1.0000
3:94035435:TA:T	donor_gain	1.0000
3:94035437:G:GG	donor_gain	1.0000
3:94036544:T:TA	acceptor_gain	1.0000
3:94036547:TTTA:T	acceptor_loss	1.0000
3:94036550:A:AG	acceptor_gain	1.0000
3:94036550:AG:A	acceptor_gain	1.0000
3:94036551:G:GG	acceptor_gain	1.0000
3:94036551:GG:G	acceptor_gain	1.0000
3:94036551:GGA:G	acceptor_gain	1.0000
3:94036551:GGAA:G	acceptor_gain	1.0000
3:94036551:GGAAC:G	acceptor_gain	1.0000
3:94036750:GAAAG:G	donor_gain	1.0000
3:94036751:AAAG:A	donor_gain	1.0000
3:94036752:AAG:A	donor_gain	1.0000
3:94036753:AG:A	donor_gain	1.0000
3:94036754:GG:G	donor_gain	1.0000
3:94036755:G:GG	donor_gain	1.0000
3:94039871:A:AG	acceptor_gain	1.0000
3:94039871:AAAC:A	acceptor_gain	1.0000
3:94039872:A:AG	acceptor_gain	1.0000
3:94039872:AAC:A	acceptor_gain	1.0000

AlphaMissense

2814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:94035342:A:T	K131I	0.999
3:93995915:A:T	K34I	0.998
3:94003772:T:A	W82R	0.998
3:94003772:T:C	W82R	0.998
3:94003799:G:T	G91W	0.998
3:94035343:A:C	K131N	0.998
3:94035343:A:T	K131N	0.998
3:93995896:G:A	G28R	0.997
3:93995896:G:C	G28R	0.997
3:93995897:G:A	G28E	0.997
3:93995914:A:C	K34Q	0.997
3:94003691:T:C	F55L	0.997
3:94003693:T:A	F55L	0.997
3:94003693:T:G	F55L	0.997
3:94003800:G:A	G91E	0.997
3:94003806:T:A	I93K	0.997
3:94003812:T:A	V95D	0.997
3:94003817:G:C	D97H	0.997
3:94003818:A:T	D97V	0.997
3:94035340:T:A	N130K	0.997
3:94035340:T:G	N130K	0.997
3:94035341:A:G	K131E	0.997
3:93995908:G:C	A32P	0.996
3:93995912:G:A	G33D	0.996
3:93995916:A:C	K34N	0.996
3:93995916:A:T	K34N	0.996
3:94003774:G:C	W82C	0.996
3:94003774:G:T	W82C	0.996
3:94003819:T:A	D97E	0.996
3:94003819:T:G	D97E	0.996

dbSNP variants (sampled 300 via entrez): RS1000062058 (3:94001648 A>G), RS1000135023 (3:94016935 G>A,T), RS1000138498 (3:94008784 G>T), RS1000205281 (3:94041027 A>G), RS1000217913 (3:94026304 T>G), RS1000301722 (3:93990344 T>C), RS1000347256 (3:94047722 C>A,T), RS1000405221 (3:94005029 A>T), RS1000419508 (3:94048077 G>A,T), RS1000448287 (3:94013576 A>G), RS1000486203 (3:94017303 G>A,T), RS1000577119 (3:93983943 A>C), RS1000596985 (3:94041272 A>G), RS1000600441 (3:94020456 C>A,G), RS1000615972 (3:94034782 T>C)

Disease associations

OMIM: gene MIM:608922 | disease phenotypes: MIM:612291, MIM:614514, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 8	Definitive	Autosomal recessive
Joubert syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Joubert syndrome	Definitive	AR

Mondo (7): Joubert syndrome 8 (MONDO:0012855), Joubert syndrome and related disorders (MONDO:0015369), thrombophilia due to protein S deficiency, autosomal recessive (MONDO:0013791), Joubert syndrome 1 (MONDO:0008944), long QT syndrome (MONDO:0002442), Joubert syndrome (MONDO:0018772), protein S deficiency (MONDO:0002304)

Orphanet (3): Isolated Joubert syndrome (Orphanet:475), Joubert syndrome and related disorders (Orphanet:140874), Severe hereditary thrombophilia due to congenital protein S deficiency (Orphanet:743)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000543	Optic disc pallor
HP:0000580	Pigmentary retinopathy
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001513	Obesity
HP:0001696	Situs inversus totalis
HP:0001829	Foot polydactyly

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D018455	Protein S Deficiency	C15.378.100.800; C15.378.147.890; C15.378.925.800
C567358	Joubert Syndrome 8 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	4
bisphenol A	decreases expression, decreases methylation	2
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1JZ	Abcam HeLa ARL13B KO	Cancer cell line	Female

Clinical trials (associated diseases)

70 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT06531525	PHASE2	NOT_YET_RECRUITING	Effect of Low Molecular Heparin on Pregnancy Outcome With Protein S Deficiency
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life