ARL8B

Summary

ARL8B (ARF like GTPase 8B, HGNC:25564) is a protein-coding gene on chromosome 3p26.1, encoding ADP-ribosylation factor-like protein 8B (Q9NVJ2). Small GTPase which cycles between active GTP-bound and inactive GDP-bound states.

Enables G protein activity; guanyl ribonucleotide binding activity; and tubulin binding activity. Involved in several processes, including antigen processing and presentation following phagocytosis; cytosolic transport; and vesicle fusion. Located in cytolytic granule membrane; midbody; and spindle midzone. Is active in early endosome membrane and lysosomal membrane.

Source: NCBI Gene 55207 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 83 total — 48 pathogenic, 3 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25564
Approved symbol	ARL8B
Name	ARF like GTPase 8B
Location	3p26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10702, Gie1
Ensembl gene	ENSG00000134108
Ensembl biotype	protein_coding
OMIM	616596
Entrez	55207

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000256496, ENST00000419534, ENST00000429403, ENST00000444332, ENST00000455168, ENST00000468010, ENST00000476343, ENST00000967326

RefSeq mRNA: 1 — MANE Select: NM_018184 NM_018184

CCDS: CCDS2566

Canonical transcript exons

ENST00000256496 — 7 exons

Exon	Start	End
ENSE00000965211	5122292	5122588
ENSE00000997172	5178664	5180911
ENSE00003469286	5174344	5174414
ENSE00003489110	5172150	5172223
ENSE00003499450	5172647	5172740
ENSE00003634424	5170503	5170583
ENSE00003664171	5174017	5174084

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.3689 / max 1087.4100, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35132	82.3689	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.26	gold quality
postcentral gyrus	UBERON:0002581	99.24	gold quality
amniotic fluid	UBERON:0000173	99.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.17	gold quality
pons	UBERON:0000988	99.12	gold quality
parietal lobe	UBERON:0001872	99.12	gold quality
gingival epithelium	UBERON:0001949	99.07	gold quality
orbitofrontal cortex	UBERON:0004167	99.07	gold quality
esophagus squamous epithelium	UBERON:0006920	99.01	gold quality
entorhinal cortex	UBERON:0002728	98.94	gold quality
superior frontal gyrus	UBERON:0002661	98.93	gold quality
gingiva	UBERON:0001828	98.89	gold quality
superior vestibular nucleus	UBERON:0007227	98.84	gold quality
medial globus pallidus	UBERON:0002477	98.81	gold quality
substantia nigra pars compacta	UBERON:0001965	98.76	gold quality
globus pallidus	UBERON:0001875	98.75	gold quality
endothelial cell	CL:0000115	98.73	gold quality
tongue squamous epithelium	UBERON:0006919	98.70	gold quality
medulla oblongata	UBERON:0001896	98.69	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.68	gold quality
epithelium of esophagus	UBERON:0001976	98.65	gold quality
squamous epithelium	UBERON:0006914	98.65	gold quality
CA1 field of hippocampus	UBERON:0003881	98.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.56	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.55	gold quality
lateral globus pallidus	UBERON:0002476	98.50	gold quality
dorsal root ganglion	UBERON:0000044	98.46	gold quality
subthalamic nucleus	UBERON:0001906	98.42	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6379	yes	509.79
E-MTAB-7249	no	8899.26
E-MTAB-9543	no	2.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

233 targeting ARL8B, 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-6867-5P	100.00	82.21	3464
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-1252-5P	100.00	69.80	2774
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-6077	99.99	68.04	2299
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762

Literature-anchored findings (GeneRIF, showing 14)

• Results suggest that the novel GTPases Gie1 and Gie2 associate with microtubules, and might be involved in chromosome segregation. (PMID:15331635)
• Arl8b is involved in trafficking processes for lysosomes. (PMID:16650381)
• Data show that with MAK3 knockdown, p53 is stabilized and phosphorylated and there is a significant transcriptional activation of proapoptotic genes downstream of p53, and that localization of Arl8b is altered, suggesting that Arl8b is a Mak3 substrate. (PMID:19398576)
• a critical regulator of cargo delivery to lysosomes (PMID:21802320)
• The authors find that Arl8B is required for kinesin-1 recruitment to Salmonella-containing vacuoles, migration of the vacuoles to the cell periphery 24 h after infection and for cell-to-cell transfer of bacteria to neighbouring cells. (PMID:21824248)
• a small GTP-binding protein, ADP-ribosylation factor-like 8b (Arl8b), is identified as a critical factor required for NK cell-mediated cytotoxicity. (PMID:24088571)
• Arl8b regulates the association of the human HOPS complex with lysosomal membranes. (PMID:25908847)
• Authors present evidence that Arl8b facilitates lipid hydrolysis to maintain efficient metabolism for a proliferative capacity in low nutrient environments, suggesting a likely explanation for the complete inability of Arl8b-depleted tumor cells to grow in vivo. (PMID:27105540)
• Data indicate that E3 ubiquitin-protein ligase RNF167 ubiquitinates Arl8B at the lysine residue K141 and reduces the level of the ADP-ribosylation factor-like 8B Arl8B protein. (PMID:27808481)
• LAMTOR1 is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning. (PMID:28993467)
• These findings suggest that membrane repair mediated by Arl8b may be an important mechanism distinguishing avirulent from virulent M. tuberculosis-induced necrotic cell death (PMID:29592961)
• Arl8b contributes to the recruitment of LAMP1 to Salmonella-induced tubules. Salmonella SifA protein interacts with Arl8b. (PMID:30212607)
• RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes. (PMID:36282215)
• ARL8B promotes hepatocellular carcinoma progression and inhibits antitumor activity of lenvatinib via MAPK/ERK signaling by interacting with RAB2A. (PMID:39413890)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arl8ba	ENSDARG00000006915
danio_rerio	arl8bb	ENSDARG00000070318
mus_musculus	Arl8b	ENSMUSG00000030105
rattus_norvegicus	Arl8b	ENSRNOG00000055860

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13B (ENSG00000169379), 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 8B — Q9NVJ2 (reviewed: Q9NVJ2)

Alternative names: ADP-ribosylation factor-like protein 10C, Novel small G protein indispensable for equal chromosome segregation 1

All UniProt accessions (4): A0A6Q8PGM9, Q9NVJ2, F2Z344, F8WAW5

UniProt curated annotations — full annotation on UniProt →

Function. Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of lysosomal positioning which is important for nutrient sensing, natural killer cell-mediated cytotoxicity and antigen presentation. Along with its effectors, orchestrates lysosomal transport and fusion. Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic granule exocytosis. Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function. Also acts as a regulator of endosome to lysosome trafficking pathways of special significance for host defense. Recruits RUFY1 onto early endosomes regulating endosomes to trans-Golgi network proteins retrieval. Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in functional assembly of the HOPS complex on lysosomal membranes. Plays an important role in cargo delivery to lysosomes for antigen presentation and microbial killing. Directs the intersection of CD1d with lipid antigens in lysosomes, and plays a role in intersecting phagosomes with lysosomes to generate phagolysosomes that kill microbes. Involved in the process of MHC II presentation. Regulates the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes allowing the fusion of late endosomes to lysosomes. May play a role in chromosome segregation. (Microbial infection) During Mycobacterium tuberculosis (Mtb) infection, is required for plasma membrane repair by controlling the exocytosis of lysosomes in macrophages. ARL8B secretion pathway is crucial to control the type of cell death of the M.tuberculosis-infected macrophages, distinguishing avirulent from virulent Mtb induced necrotic cell death. (Microbial infection) During infection, coronaviruses such as SARS-CoV-2 and the chaperone HSPA5/GRP78 are probably co-released through ARL8B-dependent lysosomal exocytic pathway for unconventional egress.

Subunit / interactions. Interacts with tubulin (PubMed:15331635, Ref.26). Interacts with BORCS5; recruits ARL8B to lysosomes. Interacts with VPS41; the interaction mediates the recruitment of the HOPS complex to lysosomes. Interacts (GTP-bound form) with PLEKHM2 (via RUN domain); the interaction is required to recruit the motor protein kinesin-1 on lysosomes. Interacts (GTP-bound form) with PLEKHM1 (via RUN domain); the interaction is required for PLEKHM1 localization to lysosomes and for ARL8B function in delivery and degradation of endocytic and autophagic cargo in lysosomes. PLEKHM1 and PLEKHM2 compete for interaction with ARL8B. Interacts (GTP-bound form) with RUFY1; the interaction is required for RUFY1 endosomal location. When GTP-bound, interacts with RUFY3 and RUFY4, but not with RUFY1, nor RUFY2.

Subcellular location. Late endosome membrane. Lysosome membrane. Cytoplasm. Cytoskeleton. Spindle. Cell projection. Axon. Synapse. Cytolytic granule membrane. Early endosome membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Ubiquitinated at Lys-141 by RNF167, leading to its degradation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NVJ2-1	1	yes
Q9NVJ2-2	2

RefSeq proteins (1): NP_060654* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR044154	Arl8a/8b	Family

Pfam: PF00025

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (34 total): mutagenesis site 10, helix 9, strand 6, binding site 3, chain 1, intramembrane region 1, turn 1, modified residue 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8JCA	X-RAY DIFFRACTION	1.65
2AL7	X-RAY DIFFRACTION	1.85
8JC5	X-RAY DIFFRACTION	2.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVJ2-F1	92.24	0.77

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): 29–35; 71–75; 130–133

Post-translational modifications (2): 1, 141

Mutagenesis-validated functional residues (10):

Position	Phenotype
5–12	diffuse cytoplasmic distribution and loss of localization to lysosomes. no effect on acetylation.
34	binds gdp, hence is inactive. alters chromosome segregation. decreases interaction with vps41. loss of lysosomal locatio
49–58	alters chromosome segregation.
70	preferentially binds gtp.
74–85	alters chromosome segregation.
75	prevents gtp hydrolysis, hence remains active. no effect on lysosomal location. alters lysosomes cellular distribution a
130	loss of gtp/gdp-binding. affects chromosome segregation.
141	abolished ubiquitination by rnf167.
2	diffuse cytoplasmic distribution and loss of localization to lysosomes. no effect on acetylation.
2	no effect on localization and acetylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 329 (showing top): MODULE_97, GCM_MAP4K4, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, CMYB_01, TTTGTAG_MIR520D, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_VACUOLAR_TRANSPORT

GO Biological Process (19): plasma membrane repair (GO:0001778), antigen processing and presentation of polysaccharide antigen via MHC class II (GO:0002505), antigen processing and presentation following phagocytosis (GO:0002747), chromosome segregation (GO:0007059), anterograde axonal transport (GO:0008089), protein transport (GO:0015031), lysosome localization (GO:0032418), early endosome to Golgi transport (GO:0034498), natural killer cell mediated cytotoxicity (GO:0042267), viral exocytosis (GO:0046754), cell division (GO:0051301), autophagosome-lysosome fusion (GO:0061909), endosome to lysosome transport of low-density lipoprotein particle (GO:0090117), phagosome-lysosome fusion (GO:0090385), late endosome to lysosome transport (GO:1902774), protein localization to early endosome (GO:1902946), calcium ion regulated lysosome exocytosis (GO:1990927), endosomal transport (GO:0016197), endosomal vesicle fusion (GO:0034058)

GO Molecular Function (9): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), alpha-tubulin binding (GO:0043014), beta-tubulin binding (GO:0048487), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (18): cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), cytosol (GO:0005829), membrane (GO:0016020), midbody (GO:0030496), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), synapse (GO:0045202), spindle midzone (GO:0051233), extracellular exosome (GO:0070062), cytolytic granule membrane (GO:0101004), axon cytoplasm (GO:1904115), endosome (GO:0005768), spindle (GO:0005819), cytoskeleton (GO:0005856), axon (GO:0030424), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
vesicle fusion	3
guanyl ribonucleotide binding	2
tubulin binding	2
endosome membrane	2
intracellular membraneless organelle	2
plasma membrane organization	1
wound healing	1
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1
antigen processing and presentation	1
cell cycle process	1
axonal transport	1
axon cytoplasm	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
vacuolar localization	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
non-lytic viral release	1
cellular process	1
macroautophagy	1
endosome to lysosome transport	1
vesicle-mediated cholesterol transport	1
phagolysosome assembly	1
lysosomal transport	1
intercellular transport	1
protein localization to endosome	1
calcium-ion regulated exocytosis	1
vesicle-mediated transport	1
intracellular transport	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

2307 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL8B	PLEKHM2	Q8IWE5	897
ARL8B	PLEKHM1	Q9Y4G2	894
ARL8B	KIF5B	P33176	820
ARL8B	LAMP1	P11279	710
ARL8B	KXD1	Q9BQD3	677
ARL8B	BORCS5	Q969J3	655
ARL8B	BORCS8	Q96FH0	632
ARL8B	LAMTOR2	Q9Y2Q5	623
ARL8B	VPS39	Q96JC1	622
ARL8B	BORCS7	Q96B45	618
ARL8B	BORCS6	Q96GS4	604
ARL8B	BLOC1S1	P78537	576
ARL8B	BLOC1S2	Q6QNY1	571
ARL8B	FYCO1	Q9BQS8	565
ARL8B	SNAPIN	O95295	565

IntAct

140 interactions, top by confidence:

A	B	Type	Score
PDCD6IP	CEP55	psi-mi:“MI:0914”(association)	0.960
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
PLEKHM1	VPS41	psi-mi:“MI:0914”(association)	0.740
PLEKHM1	ARL8B	psi-mi:“MI:0915”(physical association)	0.710
PLEKHM1	ARL8B	psi-mi:“MI:0407”(direct interaction)	0.710
ARL8B	PLEKHM1	psi-mi:“MI:0403”(colocalization)	0.710
ARL8B	PLEKHM1	psi-mi:“MI:0407”(direct interaction)	0.710
ARL8B	PLEKHM1	psi-mi:“MI:0915”(physical association)	0.710
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
SNW1	ARL8B	psi-mi:“MI:0915”(physical association)	0.620
ARL8B	SNW1	psi-mi:“MI:0915”(physical association)	0.620
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
RAB7A	ARL8B	psi-mi:“MI:0914”(association)	0.600
ARL8B	RAB7A	psi-mi:“MI:0914”(association)	0.600
SLC30A8	ARL8B	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	ARL8B	psi-mi:“MI:0915”(physical association)	0.560
ARL8B	CIDEB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (266): ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Co-fractionation), ARL8B (Co-fractionation), ARL8B (Co-fractionation), ARL8B (Co-fractionation), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ARL8B (Affinity Capture-MS)

ESM2 similar proteins: A8ISN6, B5FYQ0, O08697, O48649, O48920, P0CM16, P0CM17, P0DH91, P36397, P36404, P36405, P37996, P40617, P40940, P49076, P51821, P51822, P51823, P61213, P61214, Q06396, Q06849, Q19705, Q1MTE5, Q2KI07, Q2TA37, Q2TBW6, Q3T0M9, Q4R4S4, Q52NJ4, Q54R04, Q5R6E7, Q5ZKQ8, Q627K4, Q66HA6, Q6NZW8, Q6P8C8, Q8QHI3, Q8VEH3, Q8VY57

Diamond homologs: A8ISN6, B5FYQ0, F4IZ82, O08697, O23778, O48649, O48920, P0CM16, P0CM17, P0CR30, P0CR31, P0DH91, P11076, P18085, P19146, P22274, P25160, P26990, P26991, P34727, P36397, P36404, P36579, P38116, P40616, P40940, P40946, P49076, P49702, P51643, P51645, P51821, P51822, P51823, P51824, P61204, P61205, P61206, P61207, P61209

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	3
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047886	GRCh37/hg19 3p26.3-26.1(chr3:73914-5940479)	Pathogenic
144853	GRCh38/hg38 3p26.3-26.1(chr3:32241-5791120)x1	Pathogenic
146281	GRCh38/hg38 3p26.3-26.1(chr3:52266-5138262)x1	Pathogenic
147406	GRCh38/hg38 3p26.2-26.1(chr3:2920886-5861108)x1	Pathogenic
147496	GRCh38/hg38 3p26.3-26.1(chr3:52266-6277604)x1	Pathogenic
149085	GRCh38/hg38 3p26.3-25.2(chr3:32241-12681483)x1	Pathogenic
149236	GRCh38/hg38 3p26.3-26.1(chr3:32241-7056717)x1	Pathogenic
149331	GRCh38/hg38 3p26.3-25.3(chr3:32241-11379835)x1	Pathogenic
149555	GRCh38/hg38 3p26.3-26.1(chr3:32241-6065999)x1	Pathogenic
150031	GRCh38/hg38 3p26.3-25.1(chr3:32241-13613818)x3	Pathogenic
150281	GRCh38/hg38 3p26.3-25.3(chr3:52747-8370373)x1	Pathogenic
151534	GRCh38/hg38 3p26.3-25.3(chr3:32241-9574994)x1	Pathogenic
152256	GRCh38/hg38 3p26.3-25.3(chr3:32241-9066287)x1	Pathogenic
1526966	GRCh37/hg19 3p26.3-25.3(chr3:61891-9797094)	Pathogenic
153151	GRCh38/hg38 3p26.2-26.1(chr3:2891585-5911622)x1	Pathogenic
153284	GRCh38/hg38 3p26.3-25.3(chr3:20213-11221602)x1	Pathogenic
154175	GRCh38/hg38 3p26.3-25.3(chr3:20213-9362037)x1	Pathogenic
154452	GRCh38/hg38 3p26.3-26.1(chr3:52266-5966084)x3	Pathogenic
155106	GRCh38/hg38 3p26.3-25.3(chr3:32241-10631310)x1	Pathogenic
155258	GRCh38/hg38 3p26.3-25.3(chr3:32241-10323124)x1	Pathogenic
155639	GRCh38/hg38 3p26.3-25.3(chr3:688897-11051142)x1	Pathogenic
1803810	GRCh37/hg19 3p26.3-25.3(chr3:60931-10687964)x3	Pathogenic
1807765	GRCh37/hg19 3p26.3-25.3(chr3:61892-9899605)x1	Pathogenic
1808299	GRCh37/hg19 3p26.3-25.3(chr3:61892-11679509)x1	Pathogenic
2580893	GRCh37/hg19 3p26.2-25.3(chr3:3691505-9917651)x1	Pathogenic
2671609	Single allele	Pathogenic
2671618	Single allele	Pathogenic
3062676	GRCh37/hg19 3p26.2-26.1(chr3:3282609-5207411)x1	Pathogenic
4279259	GRCh37/hg19 3p26.3-25.3(chr3:61892-10562002)x1	Pathogenic
442243	GRCh37/hg19 3p26.3-26.1(chr3:61891-7865381)x1	Pathogenic

SpliceAI

1132 predictions. Top by Δscore:

Variant	Effect	Δscore
3:5122586:GCG:G	donor_gain	1.0000
3:5122589:G:GG	donor_gain	1.0000
3:5170496:T:TA	acceptor_gain	1.0000
3:5170501:A:AG	acceptor_gain	1.0000
3:5170502:G:GT	acceptor_gain	1.0000
3:5170502:GT:G	acceptor_gain	1.0000
3:5170502:GTC:G	acceptor_gain	1.0000
3:5170502:GTCA:G	acceptor_gain	1.0000
3:5172145:TAAA:T	acceptor_loss	1.0000
3:5172147:A:G	acceptor_gain	1.0000
3:5172147:AAGAT:A	acceptor_loss	1.0000
3:5172148:A:G	acceptor_gain	1.0000
3:5172148:A:T	acceptor_loss	1.0000
3:5172149:G:A	acceptor_loss	1.0000
3:5172149:G:GG	acceptor_gain	1.0000
3:5172149:GAT:G	acceptor_gain	1.0000
3:5172149:GATCT:G	acceptor_gain	1.0000
3:5172220:TTGT:T	donor_gain	1.0000
3:5172222:GT:G	donor_gain	1.0000
3:5172224:G:GG	donor_gain	1.0000
3:5172644:A:AG	acceptor_gain	1.0000
3:5172645:A:AG	acceptor_gain	1.0000
3:5172646:G:GG	acceptor_gain	1.0000
3:5172739:CA:C	donor_gain	1.0000
3:5172740:AGTA:A	donor_loss	1.0000
3:5172741:G:GG	donor_gain	1.0000
3:5172741:G:T	donor_loss	1.0000
3:5172742:TA:T	donor_loss	1.0000
3:5172743:AA:A	donor_loss	1.0000
3:5174071:C:G	donor_gain	1.0000

AlphaMissense

1222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:5122544:G:A	G27R	1.000
3:5122544:G:C	G27R	1.000
3:5122544:G:T	G27W	1.000
3:5122545:G:A	G27E	1.000
3:5122566:C:T	T34I	1.000
3:5170540:G:A	G54D	1.000
3:5170542:T:C	F55L	1.000
3:5170544:C:A	F55L	1.000
3:5170544:C:G	F55L	1.000
3:5172156:G:C	D71H	1.000
3:5172157:A:C	D71A	1.000
3:5172157:A:T	D71V	1.000
3:5172177:T:C	F78L	1.000
3:5172179:T:A	F78L	1.000
3:5172179:T:G	F78L	1.000
3:5172189:T:A	W82R	1.000
3:5172189:T:C	W82R	1.000
3:5172191:G:C	W82C	1.000
3:5172191:G:T	W82C	1.000
3:5174037:G:C	K131N	1.000
3:5174037:G:T	K131N	1.000
3:5122545:G:T	G27V	0.999
3:5122559:G:C	G32R	0.999
3:5122560:G:A	G32D	0.999
3:5122560:G:T	G32V	0.999
3:5122562:A:C	K33Q	0.999
3:5122563:A:T	K33M	0.999
3:5122564:G:C	K33N	0.999
3:5122564:G:T	K33N	0.999
3:5170534:C:T	T52I	0.999

dbSNP variants (sampled 300 via entrez): RS1000007277 (3:5148683 C>T), RS1000092948 (3:5135928 A>C), RS1000142054 (3:5121641 C>T), RS1000152136 (3:5133723 T>G), RS1000205079 (3:5133428 G>A), RS1000215444 (3:5143829 T>A), RS1000325943 (3:5123681 A>G), RS1000383762 (3:5176264 T>C), RS1000411421 (3:5158911 A>G), RS1000458754 (3:5165629 T>C), RS1000484264 (3:5143522 A>G), RS1000491938 (3:5133883 C>G), RS1000534164 (3:5170140 T>A,C), RS1000647676 (3:5176029 A>G), RS1000650003 (3:5140121 T>G)

Disease associations

OMIM: gene MIM:616596 | disease phenotypes: MIM:613792

GenCC curated gene-disease

Mondo (2): breast ductal adenocarcinoma (MONDO:0005590), 3p- syndrome (MONDO:0013424)

Orphanet (1): Distal deletion 3p syndrome (Orphanet:1620)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001687_17	Disc degeneration (lumbar)	7.000000e-06
GCST007433_1	Fulminant type 1 diabetes	6.000000e-06
GCST009391_1649	Metabolite levels	3.000000e-07
GCST009391_1919	Metabolite levels	3.000000e-06
GCST90011900_83	Serum alkaline phosphatase levels	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010469	carnitine measurement
EFO:0010464	beta-aminoisobutyric acid measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
C536804	Chromosome 3, monosomy 3p (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295962 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol A	affects expression, affects methylation, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
sodium arsenite	affects expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118596	Binding	Binding affinity to ARL8B in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1K1	Abcam HeLa ARL8B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery