ARL6 (ARF like GTPase 6)

Gene

• Entrez ID: 84100
• Gene name: ARF like GTPase 6
• Gene symbol: ARL6
• Synonyms (NCBI Gene): BBS3, RP55
• Chromosome: 3
• Chromosome location: 3q11.2
• Summary: The protein encoded by this gene belongs to the ARF-like (ADP ribosylation factor-like) sub-family of the ARF family of GTP-binding proteins which are involved in regulation of intracellular traffic. Mutations in this gene are associated with Bardet-Biedl

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104893678	C>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs104893679	G>C,T	Pathogenic, risk-factor	Non coding transcript variant, missense variant, intron variant, coding sequence variant
rs104893680	C>G,T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs104893681	T>C,G	Pathogenic	Non coding transcript variant, missense variant, intron variant, coding sequence variant
rs137854907	T>C	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs587777805	C>G,T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs765715798	G>A	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs771054395	T>C	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs888140182	T>A,C	Likely-pathogenic	Stop gained, synonymous variant, coding sequence variant, non coding transcript variant
rs1057515576	TAT>GAAAA	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1559679965	G>C	Pathogenic	Splice donor variant
rs1576465252	TTTTCTCTTTTA>-	Likely-pathogenic	Intron variant, splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT046980	hsa-miR-218-5p	CLASH	23622248
MIRT798375	hsa-miR-3163	CLIP-seq
MIRT798376	hsa-miR-487a	CLIP-seq
MIRT798377	hsa-miR-656	CLIP-seq
MIRT1935772	hsa-miR-4645-3p	CLIP-seq
MIRT1935773	hsa-miR-4789-3p	CLIP-seq
MIRT1935774	hsa-miR-642b	CLIP-seq
MIRT2479155	hsa-miR-105	CLIP-seq
MIRT2479156	hsa-miR-1233	CLIP-seq
MIRT2479157	hsa-miR-129-3p	CLIP-seq
MIRT2479158	hsa-miR-1304	CLIP-seq
MIRT2479159	hsa-miR-1321	CLIP-seq
MIRT2479160	hsa-miR-3126-5p	CLIP-seq
MIRT2479161	hsa-miR-3161	CLIP-seq
MIRT2479162	hsa-miR-3162-5p	CLIP-seq
MIRT2479163	hsa-miR-3668	CLIP-seq
MIRT2479164	hsa-miR-3684	CLIP-seq
MIRT2479165	hsa-miR-4419a	CLIP-seq
MIRT2479166	hsa-miR-4510	CLIP-seq
MIRT2479167	hsa-miR-4511	CLIP-seq
MIRT2479168	hsa-miR-4739	CLIP-seq
MIRT2479169	hsa-miR-4756-5p	CLIP-seq
MIRT1935773	hsa-miR-4789-3p	CLIP-seq
MIRT2479170	hsa-miR-543	CLIP-seq
MIRT2479171	hsa-miR-548b-3p	CLIP-seq
MIRT2479172	hsa-miR-548c-3p	CLIP-seq
MIRT1935774	hsa-miR-642b	CLIP-seq
MIRT798377	hsa-miR-656	CLIP-seq
MIRT2479173	hsa-miR-660	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003924	Function	GTPase activity	IEA
GO:0005515	Function	Protein binding	IPI	20603001, 22139371, 25402481, 25443296
GO:0005525	Function	GTP binding	IBA
GO:0005525	Function	GTP binding	IEA
GO:0005543	Function	Phospholipid binding	ISS
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005879	Component	Axonemal microtubule	ISS
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005929	Component	Cilium	IDA	17646400
GO:0005929	Component	Cilium	IDA	22139371
GO:0005929	Component	Cilium	TAS
GO:0005930	Component	Axoneme	IBA
GO:0005930	Component	Axoneme	ISS
GO:0006612	Process	Protein targeting to membrane	ISS
GO:0006886	Process	Intracellular protein transport	IBA
GO:0007368	Process	Determination of left/right symmetry	ISS
GO:0007420	Process	Brain development	IEA
GO:0007601	Process	Visual perception	IEA
GO:0008589	Process	Regulation of smoothened signaling pathway	IEA
GO:0010842	Process	Retina layer formation	IEA
GO:0015031	Process	Protein transport	IEA
GO:0015630	Component	Microtubule cytoskeleton	IDA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	ISS
GO:0016055	Process	Wnt signaling pathway	IMP	20207729
GO:0016192	Process	Vesicle-mediated transport	IBA
GO:0030030	Process	Cell projection organization	IEA
GO:0030117	Component	Membrane coat	ISS
GO:0032402	Process	Melanosome transport	ISS
GO:0042995	Component	Cell projection	IEA
GO:0045444	Process	Fat cell differentiation	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051258	Process	Protein polymerization	ISS
GO:0060271	Process	Cilium assembly	IBA
GO:0060271	Process	Cilium assembly	IEA
GO:0060271	Process	Cilium assembly	IMP	20207729
GO:0060271	Process	Cilium assembly	ISS
GO:0061512	Process	Protein localization to cilium	IBA
GO:0061512	Process	Protein localization to cilium	IEA
GO:0061512	Process	Protein localization to cilium	IMP	22139371
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0097499	Process	Protein localization to non-motile cilium	IEA
GO:1903445	Process	Protein transport from ciliary membrane to plasma membrane	IEA

Other IDs

• MIM: 608845
• HGNC: 13210
• e!Ensembl: ENSG00000113966

Protein

• UniProt ID: Q9H0F7
• Protein name: ADP-ribosylation factor-like protein 6 (Bardet-Biedl syndrome 3 protein)
• Protein function: Involved in membrane protein trafficking at the base of the ciliary organelle. Mediates recruitment onto plasma membrane of the BBSome complex which would constitute a coat complex required for sorting of specific membrane proteins to the primar
• PDB: 2H57
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00025	Arf	4 → 181	ADP-ribosylation factor family	Domain

• Sequence:

  MGLLDRLSVLLGLKKKEVHVLCLGLDNSGKTTIINKLKPSNAQSQNILPTIGFSIEKFKS
  SSLSFTVFDMSGQGRYRNLWEHYYKEGQAIIFVIDSSDRLRMVVAKEELDTLLNHPDIKH
  RRIPILFFANKMDLRDAVTSVKVSQLLCLENIKDKPWHICASDAIKGEGLQEGVDWLQDQ
  IQTVKT

• Sequence length: 186

Pathways

Reactome:

BBSome-mediated cargo-targeting to cilium

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the eye	Likely pathogenic	rs2108053962	RCV001814498	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ARL6-related disorder	Likely pathogenic; Pathogenic	rs2037147164, rs771628868, rs2529972867, rs771054395, rs1559679965, rs2037541934	RCV003416217 RCV004746364 RCV004747178 RCV004745430 RCV005231287 RCV004746299	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Autosomal recessive retinitis pigmentosa	Likely pathogenic	rs587777805, rs765715798	RCV001257838 RCV001257839	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Bardet-Biedl syndrome	Pathogenic; Likely pathogenic	rs104893678, rs756341249, rs765715798, rs1434357322, rs137854907, rs2037751886, rs2037752645	RCV001002871 RCV005626663 RCV002469042 RCV003222514 RCV000058868 RCV001199645 RCV001199405	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 1	Pathogenic; Likely pathogenic	rs771628868, rs104893679, rs104893680, rs765715798, rs771054395, rs137854907, rs2036471593	RCV002246376 RCV005024988 RCV005031381 RCV005024989 RCV005003523 RCV005027583 RCV005025110 RCV005037251	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 1, modifier of	Likely pathogenic; Pathogenic	rs104893679	RCV000002122	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Bardet-Biedl syndrome 3	Likely pathogenic; Pathogenic	rs2037147164, rs771628868, rs1324418374, rs2107977736, rs104893678, rs104893679, rs104893680, rs104893681, rs756341249, rs765715798, rs2529975182, rs2529972867, rs754763072, rs2529939726, rs2037378158, rs2529974016, rs1195519595, rs2529895361, rs2529896796, rs2529896839, rs2529766743, rs1057515576, rs771054395, rs1559679965, rs1576465252, rs137854907, rs1402463567, rs2037541934, rs2036471593	RCV001330111 RCV001389155 RCV001998769 RCV001987743 RCV000002120 RCV000002121 RCV000002123 RCV000002124 RCV000002125 RCV002471841 RCV001852067 RCV002962571 RCV003022773 RCV003032456 RCV003028654 RCV003782731 RCV003792133 RCV003808000 RCV003803380 RCV003800281 RCV003810119 RCV003817760 RCV003810040 RCV000408905 RCV001376735 RCV000698473 RCV000812355 RCV003764740 RCV001068039 RCV001879934 RCV005037251	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinal dystrophy	Pathogenic; Likely pathogenic	rs104893678, rs104893680, rs2529941574	RCV004814794 RCV004814795 RCV003890801	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis pigmentosa	Pathogenic; Likely pathogenic	rs104893680, rs771054395	RCV001723532 RCV000504758	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis pigmentosa 55	Likely pathogenic; Pathogenic	rs2037147164, rs771628868, rs1324418374, rs2107977736, rs104893678, rs104893679, rs104893680, rs587777805, rs756341249, rs765715798, rs2529975182, rs2529972867, rs754763072, rs2529939726, rs2037378158, rs2529974016, rs1195519595, rs2529895361, rs2529896796, rs2529896839, rs2529766743, rs2529939513, rs771054395, rs1559679965, rs1576465252, rs137854907, rs1402463567, rs2037541934, rs2036471593	RCV001859272 RCV001389155 RCV001998769 RCV001987743 RCV002512667 RCV002512668 RCV001851573 RCV001063683 RCV000002126 RCV003775513 RCV001852067 RCV002962571 RCV003022773 RCV003032456 RCV003028654 RCV003782731 RCV003792133 RCV003808000 RCV003803380 RCV003800281 RCV003810119 RCV003817760 RCV003810040 RCV004006258 RCV001376735 RCV000698473 RCV000812355 RCV003764740 RCV001068039 RCV001255192 RCV005037251	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CILIOPATHY	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONE-ROD DYSTROPHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone-rod dystrophy	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic atrophy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
RETINITIS PIGMENTOSA 1	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinitis Pigmentosa, Recessive	Likely benign; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Bardet-Biedl Syndrome	Bardet-Biedl Syndrome	BEFREE	11050632, 15314642, 15917208, 19236846, 20207729, 23219996, 9714014, 9888993		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl Syndrome	Bardet-Biedl Syndrome	LHGDN	15314642		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome	Bardet-Biedl Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl Syndrome	Bardet-Biedl Syndrome	GENOMICS_ENGLAND_DG	21282186		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl Syndrome	Bardet-Biedl Syndrome	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 1 (disorder)	Bardet-Biedl Syndrome	GENOMICS_ENGLAND_DG	15258860, 19097054, 19956407		★☆☆☆☆ Found in Text Mining only
Bardet-Biedl syndrome 3	Bardet-Biedl Syndrome	BEFREE	15258860, 20333246		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 3	Bardet-Biedl Syndrome	GENOMICS_ENGLAND_DG	15258860, 19097054, 19858128		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 3	Bardet-Biedl Syndrome	CLINVAR_DG	15258860		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 3	Bardet-Biedl Syndrome	UNIPROT_DG	15258860, 15314642, 23219996		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Bardet-Biedl syndrome 3	Bardet-Biedl Syndrome	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	38169538	Stimulate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cone Dystrophy	Cone Dystrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of kidney	Renal hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of ovary	Hypoplasia of the ovary	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deafness Autosomal Recessive 31	Deafness	Pubtator	29806606	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG	19097054		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary hemochromatosis	Hereditary Hemochromatosis	BEFREE	31465935		★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	15314642		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratoconus	Keratoconus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micropenis	Micropenis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Multicystic Dysplastic Kidney	Multicystic renal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	BEFREE	15690372		★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nijmegen Breakage Syndrome	Nijmegen Breakage Syndrome	BEFREE	9888993		★☆☆☆☆ Found in Text Mining only
Nyctalopia	Nyctalopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Polydactyly	Polydactyly	GENOMICS_ENGLAND_DG	19858128		★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
POLYDACTYLY, POSTAXIAL	Polydactyly	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Retinal Degeneration	Retinal degeneration	Pubtator	28130426	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal Diseases	BEFREE	17065527		★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	BEFREE	31736247		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	19956407		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	19956407	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis pigmentosa	Retinitis Pigmentosa	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	GENOMICS_ENGLAND_DG	21282186		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	CLINVAR_DG	23219996		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
RETINITIS PIGMENTOSA 55	Retinitis Pigmentosa	GENOMICS_ENGLAND_DG	15258860, 19097054, 19956407		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 55	Retinitis Pigmentosa	CLINVAR_DG	15258860		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 55	Retinitis Pigmentosa	UNIPROT_DG	19956407		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 55	Retinitis Pigmentosa	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Rod-Cone Dystrophy	Rod-cone dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Speech Disorders	Speech Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Speech Disorders	Speech Disorders	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Syndactyly of fingers	Syndactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ulnar polydactyly of fingers	Postaxial hand polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only