ARL16

Summary

ARL16 (ARF like GTPase 16, HGNC:27902) is a protein-coding gene on chromosome 17q25.3, encoding ADP-ribosylation factor-like protein 16 (Q0P5N6). Required for the trafficking of ciliary proteins IFT140 and INPP5E from the Golgi to the cilia, thus playing a role in ciliogenesis.

The protein encoded by this gene belongs to the ARL (ADP-ribosylation factor-like) family of proteins, which are structurally related to ADP-ribosylation factors (ARFs). This protein has been shown to have an inhibitory role in the cellular antiviral response. This gene product interacts with the C-terminal domain of the DEXD/H-box helicase 58 (DDX58) gene product. This interaction was found to suppress the association between the DDX58 gene product and RNA, thereby negatively regulating the activity of the DDX58 gene product.

Source: NCBI Gene 339231 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 48 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001040025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27902
Approved symbol	ARL16
Name	ARF like GTPase 16
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214087
Ensembl biotype	protein_coding
OMIM	619117
Entrez	339231

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000570561, ENST00000570910, ENST00000571082, ENST00000572704, ENST00000572937, ENST00000573392, ENST00000573569, ENST00000573715, ENST00000574938, ENST00000576135, ENST00000576914, ENST00000577142, ENST00000622299

RefSeq mRNA: 3 — MANE Select: NM_001040025 NM_001040025, NM_001329608, NM_001329609

CCDS: CCDS45813, CCDS86652

Canonical transcript exons

ENST00000622299 — 5 exons

Exon	Start	End
ENSE00003470948	81683013	81683126
ENSE00003642909	81682034	81682149
ENSE00003644564	81683536	81683594
ENSE00003737066	81683693	81683797
ENSE00003753134	81681187	81681879

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6822 / max 118.9985, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168779	21.8979	1819
168780	1.4131	931
168781	0.3712	129

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	94.11	gold quality
prefrontal cortex	UBERON:0000451	93.57	gold quality
right uterine tube	UBERON:0001302	93.57	gold quality
cortex of kidney	UBERON:0001225	92.85	gold quality
anterior cingulate cortex	UBERON:0009835	92.80	gold quality
frontal cortex	UBERON:0001870	92.76	gold quality
temporal lobe	UBERON:0001871	92.73	gold quality
amygdala	UBERON:0001876	92.72	gold quality
Ammon’s horn	UBERON:0001954	92.48	gold quality
right lobe of liver	UBERON:0001114	92.33	gold quality
cerebral cortex	UBERON:0000956	92.30	gold quality
right frontal lobe	UBERON:0002810	91.99	gold quality
nucleus accumbens	UBERON:0001882	91.87	gold quality
endocervix	UBERON:0000458	91.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.70	gold quality
cortical plate	UBERON:0005343	91.66	gold quality
fundus of stomach	UBERON:0001160	91.58	gold quality
adult mammalian kidney	UBERON:0000082	91.55	gold quality
putamen	UBERON:0001874	91.54	gold quality
body of pancreas	UBERON:0001150	91.50	gold quality
body of stomach	UBERON:0001161	91.46	gold quality
ectocervix	UBERON:0012249	91.44	gold quality
brain	UBERON:0000955	91.43	gold quality
stromal cell of endometrium	CL:0002255	91.37	gold quality
substantia nigra	UBERON:0002038	91.25	gold quality
right lobe of thyroid gland	UBERON:0001119	91.19	gold quality
apex of heart	UBERON:0002098	91.13	gold quality
lower esophagus mucosa	UBERON:0035834	91.11	gold quality
right coronary artery	UBERON:0001625	91.10	gold quality
caudate nucleus	UBERON:0001873	91.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.91
E-MTAB-6524	no	127.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting ARL16, 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-6778-3P	99.96	67.29	2693
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-208A-3P	95.87	66.51	397
HSA-MIR-208B-3P	95.87	66.56	396

Literature-anchored findings (GeneRIF, showing 1)

• ARF-like protein 16 (ARL16) inhibits RIG-I by binding with its C-terminal domain in a GTP-dependent manner (PMID:21233210)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arl16	ENSMUSG00000057594
rattus_norvegicus	Arl16	ENSRNOG00000049235

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), ARL13B (ENSG00000169379), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL17B (ENSG00000228696)

Protein

Protein identifiers

ADP-ribosylation factor-like protein 16 — Q0P5N6 (reviewed: Q0P5N6)

All UniProt accessions (4): B4E3H0, I3L196, I3L4Z1, I3L4Z7

UniProt curated annotations — full annotation on UniProt →

Function. Required for the trafficking of ciliary proteins IFT140 and INPP5E from the Golgi to the cilia, thus playing a role in ciliogenesis. Suppresses the RNA sensing activity of RIGI in a GTP-dependent manner.

Subunit / interactions. Interacts with RIGI; this interaction is GTP-dependent and induced upon viral infection; this interaction suppresses the RNA sensing activity of RIGI.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Mitochondrion. Cilium basal body. Photoreceptor inner segment.

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

RefSeq proteins (3): NP_001035114, NP_001316537, NP_001316538 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006689	Small_GTPase_ARF/SAR	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00025

UniProt features (6 total): binding site 4, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0P5N6-F1	86.91	0.75

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 (4): 6–13; 37–40; 61; 115–118

Mutagenesis-validated functional residues (1):

Position	Phenotype
13	loss of the inhibition of rigi-mediated antiviral response activity. loss of gtp binding activity. loss of interaction w

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, GSE13522_WT_VS_IFNG_KO_SKIN_UP, ASH1L_TARGET_GENES, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, ELF2_TARGET_GENES, LHX9_TARGET_GENES, SOX3_TARGET_GENES, ZNF282_TARGET_GENES, ZNF407_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (3): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL16	ARL9	Q6T311	707
ARL16	ARL13A	Q5H913	685
ARL16	ARL10	Q8N8L6	645
ARL16	ARL11	Q969Q4	540
ARL16	RNF125	Q96EQ8	526
ARL16	ARL4A	P40617	507
ARL16	SRPRB	Q9Y5M8	505
ARL16	USP21	Q9UK80	472
ARL16	ARL17B	I3L3L1	448
ARL16	ARL17A	Q8IVW1	447
ARL16	IRF2BP1	Q8IU81	443
ARL16	ARL4C	P56559	402
ARL16	ARL13B	Q3SXY8	393
ARL16	ARL4D	P49703	374
ARL16	DENND10	Q8TCE6	374

IntAct

118 interactions, top by confidence:

A	B	Type	Score
PDE6D	ARL16	psi-mi:“MI:0915”(physical association)	0.790
ARL16	PDE6D	psi-mi:“MI:0915”(physical association)	0.790
ARL16	AMPH	psi-mi:“MI:0915”(physical association)	0.780
ARL16	GOLGA2	psi-mi:“MI:0915”(physical association)	0.780
AMPH	ARL16	psi-mi:“MI:0915”(physical association)	0.780
GOLGA2	ARL16	psi-mi:“MI:0915”(physical association)	0.780
ARL16	TCF12	psi-mi:“MI:0915”(physical association)	0.560
ARL16	GLYR1	psi-mi:“MI:0915”(physical association)	0.560
REL	ARL16	psi-mi:“MI:0915”(physical association)	0.560
DEUP1	ARL16	psi-mi:“MI:0915”(physical association)	0.560
TCF4	ARL16	psi-mi:“MI:0915”(physical association)	0.560
ARL16	APBB2	psi-mi:“MI:0915”(physical association)	0.560
ARL16	APP	psi-mi:“MI:0915”(physical association)	0.560
ARL16		psi-mi:“MI:0915”(physical association)	0.560
PRKN	ARL16	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (87): ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), ARL16 (Two-hybrid), UBB (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS), CARD9 (Affinity Capture-MS), RHOA (Affinity Capture-MS)

ESM2 similar proteins: A1L1L6, A2A825, A6QL63, C9J798, O14908, O43374, O94844, O95278, O95294, Q0P5N6, Q15126, Q1LVW0, Q2HJF8, Q2TBH1, Q3UMR5, Q3UNW5, Q4R4U1, Q5E9M9, Q5R5F8, Q5ZIW1, Q5ZM73, Q5ZM83, Q66JN8, Q6DFV5, Q6GQW0, Q6IE70, Q6NVC5, Q6NYU2, Q7TSA0, Q7Z6G3, Q8BG51, Q8BGF7, Q8BHT7, Q8CIW5, Q8IXI1, Q8IXI2, Q8JZN7, Q8VCX6, Q91XQ2, Q923S8

Diamond homologs: A1D4D1, A3LTA2, O45379, P0C583, P0C951, P0CT16, P0CT17, P20606, P25160, P34212, P40616, P61211, P61212, Q01475, Q06849, Q0CUN7, Q0P5N6, Q20758, Q2YDM1, Q4P0I7, Q4WJS7, Q6BVA7, Q6CB54, Q6FUZ9, Q80ZU0, Q877B9, Q8VY57, Q93Y31, Q9P4C8, Q9SHU5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of apoptotic process	5	12.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2424499	NC_000017.10:g.(?79618104)(79674270_?)del	Pathogenic
57263	GRCh38/hg38 17q25.3(chr17:78901959-83086677)x3	Pathogenic
208393	NM_001040025.3(ARL16):c.-41G>T	Likely pathogenic

SpliceAI

779 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81681875:GGTCG:G	acceptor_gain	1.0000
17:81681877:TCG:T	acceptor_gain	1.0000
17:81681878:CG:C	acceptor_gain	1.0000
17:81681878:CGC:C	acceptor_gain	1.0000
17:81681880:C:CC	acceptor_gain	1.0000
17:81682010:C:CA	donor_gain	1.0000
17:81682032:A:AC	donor_gain	1.0000
17:81682033:C:CC	donor_gain	1.0000
17:81682146:CAAA:C	acceptor_gain	1.0000
17:81682150:C:CC	acceptor_gain	1.0000
17:81681876:GTCG:G	acceptor_gain	0.9900
17:81681877:TCGC:T	acceptor_loss	0.9900
17:81681881:T:A	acceptor_loss	0.9900
17:81682018:G:C	donor_gain	0.9900
17:81682030:GTACA:G	donor_loss	0.9900
17:81682031:TACA:T	donor_loss	0.9900
17:81682032:ACATT:A	donor_loss	0.9900
17:81682033:CA:C	donor_gain	0.9900
17:81682033:CAT:C	donor_gain	0.9900
17:81682147:AAA:A	acceptor_gain	0.9900
17:81682148:AAC:A	acceptor_loss	0.9900
17:81682149:AC:A	acceptor_loss	0.9900
17:81682150:CTG:C	acceptor_loss	0.9900
17:81682151:T:A	acceptor_loss	0.9900
17:81682979:C:A	donor_gain	0.9900
17:81683691:AT:A	donor_gain	0.9900
17:81683692:T:TA	donor_gain	0.9900
17:81682028:GCGTA:G	donor_loss	0.9800
17:81682029:CGTA:C	donor_loss	0.9800
17:81682145:ACAAA:A	acceptor_gain	0.9800

AlphaMissense

1104 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81682037:T:A	K140I	0.998
17:81681777:G:C	S175R	0.990
17:81681777:G:T	S175R	0.990
17:81681779:T:G	S175R	0.990
17:81682039:A:C	N139K	0.990
17:81682039:A:T	N139K	0.990
17:81682049:A:T	I136K	0.990
17:81682147:A:C	F103L	0.987
17:81682147:A:T	F103L	0.987
17:81682149:A:G	F103L	0.987
17:81683077:C:G	R81P	0.986
17:81683048:A:G	W91R	0.985
17:81683048:A:T	W91R	0.985
17:81682036:T:A	K140N	0.983
17:81682036:T:G	K140N	0.983
17:81683046:C:A	W91C	0.983
17:81683046:C:G	W91C	0.983
17:81682049:A:C	I136R	0.982
17:81683722:C:A	G35V	0.982
17:81683080:A:T	I80N	0.981
17:81683722:C:T	G35E	0.981
17:81682097:A:G	L120P	0.980
17:81683718:C:A	K36N	0.979
17:81683718:C:G	K36N	0.979
17:81682038:T:C	K140E	0.977
17:81682052:A:G	L135P	0.977
17:81682037:T:G	K140T	0.976
17:81682046:A:T	L137H	0.976
17:81683068:C:A	G84V	0.976
17:81682148:A:G	F103S	0.975

dbSNP variants (sampled 300 via entrez): RS1000298277 (17:81681733 T>G), RS1000856090 (17:81684375 G>C), RS1000888873 (17:81684579 C>G,T), RS1002119525 (17:81684986 G>A), RS1002393038 (17:81684802 T>C), RS1002784331 (17:81683480 T>C), RS1002816943 (17:81683299 G>C,T), RS1002834393 (17:81684933 G>A,C), RS1003793886 (17:81684172 C>A,G), RS1003825021 (17:81684009 G>A,T), RS1004325411 (17:81684973 C>G,T), RS1004564235 (17:81684204 C>A,T), RS1004662735 (17:81684164 A>C,G), RS1005196970 (17:81682790 A>G), RS1005330699 (17:81685786 G>A,C,T)

Disease associations

OMIM: gene MIM:619117 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): childhood-onset schizophrenia (MONDO:0957430)

Orphanet (1): Childhood-onset schizophrenia (Orphanet:641496)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_133	Refractive error	2.000000e-50

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Doxorubicin	decreases expression	1
Naled	affects expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Thiram	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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