ARL3

protein-coding

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

Gene summary

Enables GDP binding activity; GTP binding activity; and microtubule binding activity. Involved in several processes, including cilium assembly; protein localization to cilium; and small GTPase-mediated signal transduction. Acts upstream of or within post-Golgi vesicle-mediated transport. Located in several cellular components, including microtubule cytoskeleton; midbody; and photoreceptor connecting cilium. Implicated in Joubert syndrome and retinitis pigmentosa 83. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_004311.4

Inheritance

AR, AD

ClinVar variants

P:7U:87B:29

Top phenotype

Joubert syndrome 35; Retinitis pigmentosa 83

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr10:102,673,731-102,714,397

External References & Databases

Ensembl (ENSG00000138175)

Transcript & Mutation Effects

hg38 • Region Span ~40.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Joubert syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018772

Submitter: Orphanet

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

Joubert syndrome 35STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032570

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosa 83LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032577

Submitter: Ambry Genetics

Joubert syndrome 35STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032570

Submitter: PanelApp Australia

retinitis pigmentosa 83MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032577

Submitter: PanelApp Australia

Joubert syndrome 35STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032570

Submitter: G2P

retinitis pigmentosa 83STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032577

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Illumina

retinitis pigmentosa 83LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032577

Submitter: G2P

Clinical Genomic Database (CGD)

Joubert syndrome 35; Retinitis pigmentosa 83AR

Manifestation: Craniofacial; Neurologic; Ophthalmologic; Renal

Intervention: General

Rationale: 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

Comments: 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

Refs: 26964041; 30269812

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARL3 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 141

not specifiedTotal: 19

Inborn genetic diseasesTotal: 19

Retinal dystrophyTotal: 8

Retinitis pigmentosa 83Total: 5

Joubert syndrome 35Total: 5

ARL3-related disorderTotal: 4

Retinitis pigmentosaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004311.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	26 clinvar	1 clinvar	29
missense	2 clinvar	5 clinvar	66 clinvar	2 clinvar		75
nonsense			5 clinvar			5
start loss			1 clinvar			1
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	2	5	87	28	1	123

Highest pathogenic variant AF is 0.000009293726

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004311.4	RefSeq	NP_004302.1	6	MANE Select
ENST00000260746.6	Ensembl	ENSP00000260746.4	6	MANE Select
ENST00000901818.1	Ensembl	ENSP00000571877.1	5	Standard
ENST00000901818.2	Ensembl	ENSP00000571877.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Trafficking of myristoylated proteins to the cilium
Cargo trafficking to the periciliary membrane
Cilium Assembly
Organelle biogenesis and maintenance

Biological Process

mitotic cytokinesis
kidney development
post-Golgi vesicle-mediated transport
Golgi to plasma membrane transport
smoothened signaling pathway

Molecular Function

magnesium ion binding
GTPase activity
protein binding
GTP binding
microtubule binding

Cellular Component

Golgi membrane
nucleus
Golgi apparatus
centrosome
spindle microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260746
Coding exons: 6
Length: 40677
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125744
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	65	97.1	0.670	0.00000500	1193
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.357
RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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