ARL2BP

Summary

ARL2BP (ARF like GTPase 2 binding protein, HGNC:17146) is a protein-coding gene on chromosome 16q13, encoding ADP-ribosylation factor-like protein 2-binding protein (Q9Y2Y0). Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3.

ADP-ribosylation factor (ARF)-like proteins (ARLs) comprise a functionally distinct group of the ARF family of RAS-related GTPases. The protein encoded by this gene binds to ARL2.GTP with high affinity but does not interact with ARL2.GDP, activated ARF, or RHO proteins. The lack of detectable membrane association of this protein or ARL2 upon activation of ARL2 is suggestive of actions distinct from those of the ARFs. This protein is considered to be the first ARL2-specific effector identified, due to its interaction with ARL2.GTP but lack of ARL2 GTPase-activating protein activity.

Source: NCBI Gene 23568 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 118 total — 14 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 43
• MANE Select transcript: NM_012106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17146
Approved symbol	ARL2BP
Name	ARF like GTPase 2 binding protein
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	BART1, BART
Ensembl gene	ENSG00000102931
Ensembl biotype	protein_coding
OMIM	615407
Entrez	23568

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000219204, ENST00000562023, ENST00000563234, ENST00000565794

RefSeq mRNA: 1 — MANE Select: NM_012106 NM_012106

CCDS: CCDS10776

Canonical transcript exons

ENST00000219204 — 6 exons

Exon	Start	End
ENSE00000685157	57248537	57248643
ENSE00000685159	57249767	57249852
ENSE00000685162	57250411	57250507
ENSE00000852885	57246080	57246141
ENSE00001306775	57252166	57253635
ENSE00001308818	57245259	57245405

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.2706 / max 265.9175, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154324	20.6901	1788
154322	13.1547	1795
154325	6.0603	1574
154321	5.4258	1592
154327	2.5726	1243
154326	1.9556	1025
154323	1.4115	1036

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.40	gold quality
smooth muscle tissue	UBERON:0001135	95.91	gold quality
ganglionic eminence	UBERON:0004023	95.75	gold quality
cortical plate	UBERON:0005343	95.36	gold quality
ventricular zone	UBERON:0003053	94.88	gold quality
right coronary artery	UBERON:0001625	94.79	gold quality
cingulate cortex	UBERON:0003027	94.68	gold quality
anterior cingulate cortex	UBERON:0009835	94.66	gold quality
islet of Langerhans	UBERON:0000006	94.39	gold quality
nucleus accumbens	UBERON:0001882	94.33	gold quality
gall bladder	UBERON:0002110	94.25	gold quality
prefrontal cortex	UBERON:0000451	94.20	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.17	gold quality
right testis	UBERON:0004534	94.16	gold quality
left testis	UBERON:0004533	94.04	gold quality
left coronary artery	UBERON:0001626	93.95	gold quality
left uterine tube	UBERON:0001303	93.93	gold quality
right adrenal gland cortex	UBERON:0035827	93.91	gold quality
caudate nucleus	UBERON:0001873	93.89	gold quality
calcaneal tendon	UBERON:0003701	93.86	gold quality
thoracic aorta	UBERON:0001515	93.85	gold quality
coronary artery	UBERON:0001621	93.84	gold quality
ascending aorta	UBERON:0001496	93.79	gold quality
right adrenal gland	UBERON:0001233	93.78	gold quality
right lung	UBERON:0002167	93.78	gold quality
amygdala	UBERON:0001876	93.70	gold quality
descending thoracic aorta	UBERON:0002345	93.66	gold quality
saphenous vein	UBERON:0007318	93.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.53	gold quality
rectum	UBERON:0001052	93.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.11
E-MTAB-10290	no	216.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting ARL2BP, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-499A-5P	99.98	70.79	1323
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

Literature-anchored findings (GeneRIF, showing 14)

• Crystal structure of the ARL2-GTP-BART complex reveals a novel recognition and binding mode of small GTPase with effector. (PMID:19368893)
• overexpression of the amino (N)-terminal region of G3BP, including the binding region for BART mRNA, dominant-negatively inhibits formation of the complex between endogenous G3BP and BART mRNA, and increases the expression of BART. (PMID:21665939)
• Our results imply that BART increases active RhoA by inhibiting ARL2 function, which in turn inhibits invasiveness of cancer cells. (PMID:21833473)
• We identify a subset of BART miRNAs that are restricted to Latency III in normal infection but are up regulated in tumors that express Latency I and II. (PMID:21901094)
• These results imply that BART contributes to regulating PKCalpha activity through binding to ANX7, thereby affecting the invasiveness of pancreatic cancer cells. (PMID:22532868)
• Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion. (PMID:22745590)
• EBV-miR-BART1 could influence the expression of metabolism-associated genes and might be involved in cancer metabolism in nasopharyngeal carcinoma (PMID:23685147)
• Mutations in ARL2BP cause autosomal-recessive retinitis pigmentosa. (PMID:23849777)
• EBV also downregulates two immediate early genes by miR-BART20-5p. (PMID:24899173)
• Subsequent analysis of 844 index cases did not reveal further pathogenic chances in ARL2BP indicating that mutations in ARL2B are a rare cause of arRCD (about 0.1%) in a large cohort of French patients. (PMID:27790702)
• This study identified two homozygous variants in ARL2BP as a rare cause of autosomal recessive retinitis pigmentosa. Further studies are required to define the underlying disease mechanism causing retinal degeneration as a result of mutations in ARL2BP and any phenotype-genotype correlation associated with residual levels of the wild-type transcript. (PMID:30210231)
• Study identified multiple ciliopathy phenotypes associated with mutations in ARL2BP in human patients and in a mouse knockout model. Spermiogenesis is impaired, resulting in abnormally shaped heads, shortened and mis-assembled sperm tails, and loss of axonemal doublets. ARL2BP is required for the structural maintenance of cilia as well as of the sperm flagellum, and that its deficiency leads to syndromic ciliopathy. (PMID:31425546)
• ARL3 activation requires the co-GEF BART and effector-mediated turnover. (PMID:33438581)
• Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3. (PMID:34681596)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arl2bp	ENSDARG00000025383
mus_musculus	Arl2bp	ENSMUSG00000031776
rattus_norvegicus	Arl2bp	ENSRNOG00000016991

Protein

Protein identifiers

ADP-ribosylation factor-like protein 2-binding protein — Q9Y2Y0 (reviewed: Q9Y2Y0)

Alternative names: Binder of ARF2 protein 1

All UniProt accessions (3): Q9Y2Y0, H3BM52, H3BU49

UniProt curated annotations — full annotation on UniProt →

Function. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2.

Subunit / interactions. Found in a complex with ARL2BP, ARL2 and SLC25A6. Found in a complex with ARL2, ARL2BP and SLC25A4. Interacts with STAT2, STAT3 and STAT4. Interacts with GTP-bound ARL2 and ARL3; the complex ARL2-ARL2BP as well as ARL2BP alone, binds to SLC25A4. Interaction with ARL2 may be required for targeting to cilia basal body. Interacts with STAT3; interaction is enhanced with ARL2.

Subcellular location. Cytoplasm. Mitochondrion intermembrane space. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleus. Spindle. Cilium basal body.

Tissue specificity. Expressed in retina pigment epithelial cells (at protein level). Widely expressed.

Disease relevance. Retinitis pigmentosa 82 with or without situs inversus (RP82) [MIM:615434] An autosomal recessive disorder characterized by variable association of retinitis pigmentosa with situs inversus. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Situs inversus is a congenital abnormality in which organs in the thorax and the abdomen are opposite to their normal positions due to lateral transposition. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ARL2BP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2Y0-1	1	yes
Q9Y2Y0-2	2

RefSeq proteins (1): NP_036238* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023379	BART_dom	Domain
IPR038849	ARL2BP	Family
IPR042541	BART_sf	Homologous_superfamily

Pfam: PF11527

UniProt features (34 total): mutagenesis site 10, helix 7, sequence conflict 6, strand 3, turn 3, splice variant 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3DOE	X-RAY DIFFRACTION	2.25
3DOF	X-RAY DIFFRACTION	3.3
2K9A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2Y0-F1	82.01	0.50

Functional residue map

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

Mutagenesis-validated functional residues (10):

Position	Phenotype
109	decreases interaction with arl2.
110	decreases interaction with arl2.
111	does not decrease interaction with arl2.
112	decreases interaction with arl2.
115	decreases interaction with arl2.
56	decreases interaction with arl2.
57	decreases interaction with arl2.
60	decreases interaction with arl2.
74	decreases interaction with arl2.
76	decreases interaction with arl2.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-83936	Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 279 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, PAL_PRMT5_TARGETS_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TATTATA_MIR374, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, CTCTAGA_MIR526C_MIR518F_MIR526A, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_MAINTENANCE_OF_LOCATION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, TGCTGAY_UNKNOWN, GOBP_MAINTENANCE_OF_PROTEIN_LOCALIZATION_IN_ORGANELLE, GOCC_CENTROSOME

GO Biological Process (4): signal transduction (GO:0007165), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), maintenance of protein location in nucleus (GO:0051457), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), GTPase regulator activity (GO:0030695), protein binding (GO:0005515)

GO Cellular Component (14): nucleoplasm (GO:0005654), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), midbody (GO:0030496), ciliary basal body (GO:0036064), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transport of vitamins, nucleosides, and related molecules	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
microtubule organizing center	2
intracellular membraneless organelle	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
positive regulation of peptidyl-tyrosine phosphorylation	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
GTPase activity	1
nucleoside-triphosphatase regulator activity	1
binding	1
nuclear lumen	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1
centriole	1
microtubule cytoskeleton	1
cilium	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL2BP	ARL2	P36404	803
ARL2BP	INTS6	Q9UL03	544
ARL2BP	CFAP418	Q96NL8	539
ARL2BP	FAM76B	Q5HYJ3	533
ARL2BP	RPGR	Q92834	506
ARL2BP	TTC8	Q8TAM2	504
ARL2BP	RP1L1	Q8IWN7	474
ARL2BP	BCL2	P10415	467
ARL2BP	ARL3	P36405	463
ARL2BP	RSPRY1	Q96DX4	460
ARL2BP	BSDC1	Q9NW68	455
ARL2BP	EAF1	Q96JC9	451
ARL2BP	BCL2L11	O43521	448
ARL2BP	MICB	P79525	448
ARL2BP	IPO7	O95373	447

IntAct

62 interactions, top by confidence:

A	B	Type	Score
ARL2BP	ARL2	psi-mi:“MI:0915”(physical association)	0.970
ARL2	ARL2BP	psi-mi:“MI:0915”(physical association)	0.970
ARL2BP	ARL2	psi-mi:“MI:0407”(direct interaction)	0.970
ARL2	ARL2BP	psi-mi:“MI:2364”(proximity)	0.970
ARL2BP	ARL3	psi-mi:“MI:0915”(physical association)	0.840
ARL3	ARL2BP	psi-mi:“MI:0915”(physical association)	0.840
ARL2BP	CFAP20	psi-mi:“MI:0915”(physical association)	0.790
ARL3	UNC119B	psi-mi:“MI:0914”(association)	0.730
ARL2BP	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
ARL2BP	GSN	psi-mi:“MI:0915”(physical association)	0.560
TCP1	ARL2BP	psi-mi:“MI:0915”(physical association)	0.560
ARL2BP		psi-mi:“MI:0915”(physical association)	0.560
ARL2BP	BAG6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	ARL2BP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (72): ARL2BP (Two-hybrid), ARL2BP (Affinity Capture-RNA), ARL2BP (Affinity Capture-RNA), ARL2BP (Affinity Capture-RNA), ARL2BP (Affinity Capture-MS), ARL2BP (Affinity Capture-MS), ARL2BP (Reconstituted Complex), ARL2 (Reconstituted Complex), ARL2BP (Affinity Capture-MS), ARL2BP (Affinity Capture-MS), ARL2BP (Affinity Capture-MS), ARL3 (Affinity Capture-MS), CFAP20 (Affinity Capture-MS), ARL2BP (Two-hybrid), ARL2BP (FRET)

ESM2 similar proteins: A2AFS3, A6QLZ5, A9YWH3, C0HME0, G3MWR8, O95684, P13668, P14745, P16949, P20944, P63042, P63043, Q05078, Q28284, Q29423, Q2KI04, Q2YDD1, Q32PC9, Q3T0C7, Q4R712, Q4R7M4, Q4R7V3, Q4R930, Q4V7C1, Q52LA3, Q5E948, Q5NVP8, Q5R4C5, Q5RCB7, Q5RE12, Q5SQY2, Q5ZJB7, Q5ZJQ3, Q5ZJV7, Q66JX5, Q6AYJ2, Q7RTP6, Q7Z422, Q7Z7L8, Q86XW9

Diamond homologs: Q32PC9, Q3ZC62, Q4R930, Q4V8C5, Q4V8E4, Q5FW25, Q5R9K8, Q5ZKW5, Q6DDX7, Q7SYL1, Q8C6E0, Q96G28, Q9D385, Q9Y2Y0, Q28IH8, Q7T0S7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	3
Uncertain significance	54
Likely benign	33
Benign	2

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1373439	NM_012106.4(ARL2BP):c.139_143dup (p.Tyr48Ter)	Pathogenic
1928800	NM_012106.4(ARL2BP):c.191del (p.Pro64fs)	Pathogenic
2116238	NM_012106.4(ARL2BP):c.97_98dup (p.Met33fs)	Pathogenic
2577503	NM_012106.4(ARL2BP):c.33_36del (p.Phe13fs)	Pathogenic
2770655	NM_012106.4(ARL2BP):c.207C>A (p.Tyr69Ter)	Pathogenic
2811446	NM_012106.4(ARL2BP):c.235G>T (p.Glu79Ter)	Pathogenic
3028367	NM_012106.4(ARL2BP):c.37_38del (p.Phe13fs)	Pathogenic
3338167	NM_012106.4(ARL2BP):c.294-1G>C	Pathogenic
3338170	NM_012106.4(ARL2BP):c.22_23del (p.Ser8fs)	Pathogenic
437946	NM_012106.4(ARL2BP):c.207+1G>A	Pathogenic
559501	NM_012106.4(ARL2BP):c.207+1G>T	Pathogenic
564331	GRCh37/hg19 16q12.2-22.2(chr16:54416050-72453266)x3	Pathogenic
65473	NM_012106.4(ARL2BP):c.101-1G>C	Pathogenic
812223	NM_012106.4(ARL2BP):c.38+2T>G	Pathogenic
1064633	NM_012106.4(ARL2BP):c.293+5G>A	Likely pathogenic
1525053	NM_012106.4(ARL2BP):c.294-17_342del	Likely pathogenic
850967	NM_012106.4(ARL2BP):c.39-1G>C	Likely pathogenic

SpliceAI

898 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57245406:G:GG	donor_gain	1.0000
16:57248527:T:A	acceptor_gain	1.0000
16:57248529:T:TA	acceptor_gain	1.0000
16:57248530:G:A	acceptor_gain	1.0000
16:57248640:ATAC:A	donor_gain	1.0000
16:57248641:TACG:T	donor_loss	1.0000
16:57248642:ACGT:A	donor_loss	1.0000
16:57248643:CG:C	donor_loss	1.0000
16:57248644:G:GG	donor_gain	1.0000
16:57248644:GTAAG:G	donor_loss	1.0000
16:57248645:TAAGT:T	donor_loss	1.0000
16:57249763:GCAGA:G	acceptor_gain	1.0000
16:57249764:CA:C	acceptor_loss	1.0000
16:57249764:CAGA:C	acceptor_gain	1.0000
16:57249765:A:AG	acceptor_gain	1.0000
16:57249765:AGATT:A	acceptor_loss	1.0000
16:57249766:G:GA	acceptor_gain	1.0000
16:57249766:GA:G	acceptor_gain	1.0000
16:57249766:GAT:G	acceptor_gain	1.0000
16:57249766:GATT:G	acceptor_gain	1.0000
16:57249766:GATTT:G	acceptor_gain	1.0000
16:57249848:TTACA:T	donor_gain	1.0000
16:57249849:TACA:T	donor_gain	1.0000
16:57249850:ACA:A	donor_gain	1.0000
16:57249851:CA:C	donor_gain	1.0000
16:57249853:G:GG	donor_gain	1.0000
16:57249853:G:T	donor_loss	1.0000
16:57249854:T:A	donor_loss	1.0000
16:57249855:GAGT:G	donor_gain	1.0000
16:57249858:T:G	donor_gain	1.0000

AlphaMissense

1080 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57250483:A:C	K122N	0.999
16:57250483:A:T	K122N	0.999
16:57250469:T:C	F118L	0.998
16:57250471:T:A	F118L	0.998
16:57250471:T:G	F118L	0.998
16:57250478:T:C	F121L	0.998
16:57250480:T:A	F121L	0.998
16:57250480:T:G	F121L	0.998
16:57248632:T:C	F66L	0.997
16:57248634:T:A	F66L	0.997
16:57248634:T:G	F66L	0.997
16:57250482:A:T	K122I	0.997
16:57248590:T:C	F52L	0.996
16:57248592:T:A	F52L	0.996
16:57248592:T:G	F52L	0.996
16:57250479:T:C	F121S	0.996
16:57248591:T:C	F52S	0.994
16:57249801:T:C	L81P	0.994
16:57250470:T:C	F118S	0.994
16:57248545:T:C	F37L	0.993
16:57248547:C:A	F37L	0.993
16:57248547:C:G	F37L	0.993
16:57249821:T:C	F88L	0.993
16:57249823:C:A	F88L	0.993
16:57249823:C:G	F88L	0.993
16:57250470:T:G	F118C	0.993
16:57248610:T:A	N58K	0.992
16:57248610:T:G	N58K	0.992
16:57246102:T:C	F21L	0.990
16:57246104:T:A	F21L	0.990

dbSNP variants (sampled 300 via entrez): RS1000212508 (16:57248727 G>A,C), RS1000601562 (16:57245097 C>A), RS1000675086 (16:57245226 G>A,C,T), RS1001262058 (16:57248238 T>C), RS1001335538 (16:57248469 C>G), RS1002105349 (16:57253470 T>G), RS1002274266 (16:57246577 C>T), RS1002616411 (16:57253747 T>C), RS1002937135 (16:57250209 G>A), RS1003005423 (16:57243428 G>A,C,T), RS1003571257 (16:57243648 G>C), RS1004563066 (16:57251709 C>T), RS1005120710 (16:57244770 T>A), RS1005198700 (16:57254076 T>C), RS1005388867 (16:57247510 A>G)

Disease associations

OMIM: gene MIM:615407 | disease phenotypes: MIM:615434, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa with or without situs inversus	Definitive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Mondo (3): retinitis pigmentosa with or without situs inversus (MONDO:0014186), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200)

Orphanet (2): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001696	Situs inversus totalis
HP:0001742	Nasal congestion
HP:0002110	Bronchiectasis
HP:0002719	Recurrent infections
HP:0003623	Neonatal onset
HP:0007401	Macular atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005992_35	Mean corpuscular hemoglobin concentration	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
Acetaminophen	increases expression	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1K0	Abcam HeLa ARL2BP KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa