ARL14

Summary

ARL14 (ARF like GTPase 14, HGNC:22974) is a protein-coding gene on chromosome 3q25.33, encoding ADP-ribosylation factor-like protein 14 (Q8N4G2). GTPase that recruits MYO1E to MHC class II-containing vesicles via the effector protein ARL14EP and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells.

Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in cytoplasmic vesicle. Predicted to be active in cytoplasm and plasma membrane.

Source: NCBI Gene 80117 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 34 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_025047

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22974
Approved symbol	ARL14
Name	ARF like GTPase 14
Location	3q25.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22595
Ensembl gene	ENSG00000179674
Ensembl biotype	protein_coding
OMIM	614439
Entrez	80117

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000320767

RefSeq mRNA: 1 — MANE Select: NM_025047 NM_025047

CCDS: CCDS3192

Canonical transcript exons

ENST00000320767 — 1 exons

Exon	Start	End
ENSE00001222314	160677160	160678448

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 97.98.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8234 / max 105.0404, expressed in 186 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39589	0.4876	134
39590	0.3359	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	97.98	gold quality
jejunal mucosa	UBERON:0000399	97.92	gold quality
colonic mucosa	UBERON:0000317	97.15	gold quality
gall bladder	UBERON:0002110	95.08	gold quality
rectum	UBERON:0001052	93.37	gold quality
duodenum	UBERON:0002114	92.73	gold quality
mucosa of transverse colon	UBERON:0004991	89.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.75	gold quality
ileal mucosa	UBERON:0000331	85.80	gold quality
pylorus	UBERON:0001166	84.97	gold quality
epithelial cell of pancreas	CL:0000083	84.39	gold quality
transverse colon	UBERON:0001157	79.32	gold quality
body of stomach	UBERON:0001161	77.89	gold quality
body of pancreas	UBERON:0001150	77.84	gold quality
mucosa of urinary bladder	UBERON:0001259	76.55	gold quality
small intestine	UBERON:0002108	76.42	gold quality
stomach	UBERON:0000945	76.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.80	gold quality
pancreas	UBERON:0001264	75.40	gold quality
jejunum	UBERON:0002115	74.05	gold quality
vermiform appendix	UBERON:0001154	73.06	gold quality
islet of Langerhans	UBERON:0000006	72.28	gold quality
colonic epithelium	UBERON:0000397	71.26	gold quality
intestine	UBERON:0000160	70.99	gold quality
urinary bladder	UBERON:0001255	70.45	gold quality
large intestine	UBERON:0000059	69.39	gold quality
fundus of stomach	UBERON:0001160	68.92	gold quality
mucosa of stomach	UBERON:0001199	68.80	gold quality
caecum	UBERON:0001153	68.23	gold quality
colon	UBERON:0001155	68.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	14.65
E-ANND-3	yes	7.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting ARL14, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-325	99.58	66.55	358
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-375-3P	97.91	65.12	483
HSA-MIR-3664-3P	97.85	67.62	1452

Literature-anchored findings (GeneRIF, showing 1)

• The amphipathic helices of Arfrp1 and Arl14 are sufficient to determine subcellular localizations. (PMID:32972971)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arl14	ENSMUSG00000098207
rattus_norvegicus	Arl14	ENSRNOG00000049827

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), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

ADP-ribosylation factor-like protein 14 — Q8N4G2 (reviewed: Q8N4G2)

Alternative names: ADP-ribosylation factor 7

All UniProt accessions (1): Q8N4G2

UniProt curated annotations — full annotation on UniProt →

Function. GTPase that recruits MYO1E to MHC class II-containing vesicles via the effector protein ARL14EP and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells.

Subunit / interactions. Interacts with ARL14EP.

Subcellular location. Cytoplasmic vesicle.

Tissue specificity. Expressed in immature dendritic cells.

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

RefSeq proteins (1): NP_079323* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR024156	Small_GTPase_ARF	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00025

UniProt features (9 total): binding site 3, sequence variant 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4G2-F1	93.19	0.83

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): 20–27; 64–68; 123–126

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, KOYAMA_SEMA3B_TARGETS_UP, BASAKI_YBX1_TARGETS_DN, SENESE_HDAC1_TARGETS_UP, RICKMAN_HEAD_AND_NECK_CANCER_C, NAGASHIMA_NRG1_SIGNALING_DN, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, chr3q25, ZHANG_RESPONSE_TO_IKK_INHIBITOR_AND_TNF_UP, WINZEN_DEGRADED_VIA_KHSRP

GO Biological Process (3): intracellular protein transport (GO:0006886), vesicle-mediated transport (GO:0016192), establishment of cell polarity (GO:0030010)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	1
protein transport	1
intracellular transport	1
transport	1
cellular process	1
establishment or maintenance of cell polarity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1821 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL14	ARL14EP	Q8N8R7	731
ARL14	PSD4	Q8NDX1	642
ARL14	FREM3	P0C091	590
ARL14	MYO1E	Q12965	586
ARL14	PLD1	Q13393	513
ARL14	LURAP1	Q96LR2	490
ARL14	RPS6KL1	Q9Y6S9	474
ARL14	HBB	P02023	457
ARL14	PPM1L	Q5SGD2	450
ARL14	INPP4B	O15327	435
ARL14	AXDND1	Q5T1B0	435
ARL14	ABCE1	P61221	425
ARL14	HBA1	P01922	409
ARL14	ATL2	Q8NHH9	404
ARL14	ATL3	Q6DD88	403

IntAct

13 interactions, top by confidence:

A	B	Type	Score
EXOC3L1	ARL14	psi-mi:“MI:0915”(physical association)	0.560
ARL14EP	ARL14	psi-mi:“MI:0915”(physical association)	0.540
ARL14	ARL14EP	psi-mi:“MI:0403”(colocalization)	0.540
ARL14	ARNT	psi-mi:“MI:0915”(physical association)	0.490
ARNT	ARL14	psi-mi:“MI:0915”(physical association)	0.490
PSD4	ARL14	psi-mi:“MI:0407”(direct interaction)	0.440
MEP1B	ARL14	psi-mi:“MI:0915”(physical association)	0.370
ARL14	UBE2G2	psi-mi:“MI:0915”(physical association)	0.370
PIP5K1A	ARL14	psi-mi:“MI:0403”(colocalization)	0.270
EXOC3L1	ARL14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (120): ARNT (Two-hybrid), ARL14 (Synthetic Lethality), ARL14 (Two-hybrid), ARL14 (Positive Genetic), PLD1 (Proximity Label-MS), CTDSP2 (Proximity Label-MS), MRPS31 (Proximity Label-MS), SLC3A2 (Proximity Label-MS), MPZL1 (Proximity Label-MS), PVRL2 (Proximity Label-MS), CASK (Proximity Label-MS), DGCR8 (Proximity Label-MS), EPB41L2 (Proximity Label-MS), MCAM (Proximity Label-MS), OCLN (Proximity Label-MS)

ESM2 similar proteins: A4D1S5, A6NH57, O45379, O59781, O88848, P25160, P25378, P34212, P38116, P40994, P51152, P51646, Q02804, Q0IIM2, Q13795, Q18510, Q2KJ96, Q32LJ2, Q3SXC5, Q54E92, Q54HK2, Q54I24, Q54JJ3, Q54V41, Q54V47, Q54Y14, Q54YV7, Q55AD9, Q5JT25, Q5M9P8, Q5R4G5, Q5R579, Q5RCQ6, Q60Z38, Q61DE0, Q63055, Q6P068, Q6P3A9, Q80ZU0, Q8BXL7

Diamond homologs: A8INQ0, A8ISN6, B5FYQ0, O04266, O04834, O08697, O23778, O45379, O48649, O48920, P0CM16, P0CM17, P0DH91, P11076, P19146, P20606, P22274, P26990, P26991, P36397, P36404, P36405, P36579, P37996, P38116, P40616, P40940, P40945, P40946, P49076, P51643, P51645, P51821, P51822, P51823, P51824, P61204, P61205, P61206, P61207

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	29
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1527050	GRCh37/hg19 3q25.32-26.33(chr3:157128738-181637333)	Pathogenic
4075931	GRCh37/hg19 3q25.31-26.1(chr3:155309468-164325380)x1	Likely pathogenic

SpliceAI

50 predictions. Top by Δscore:

Variant	Effect	Δscore
3:160677709:A:AG	acceptor_gain	0.5000
3:160677710:G:GG	acceptor_gain	0.5000
3:160677710:GCC:G	acceptor_gain	0.4100
3:160677477:CAAT:C	acceptor_gain	0.4000
3:160677478:AATA:A	acceptor_gain	0.4000
3:160677421:G:GT	donor_gain	0.3900
3:160677710:GCCAA:G	acceptor_gain	0.3900
3:160677455:AAGG:A	acceptor_gain	0.3800
3:160677456:AGGA:A	acceptor_gain	0.3800
3:160677710:GCCA:G	acceptor_gain	0.3800
3:160677457:G:C	acceptor_gain	0.3700
3:160677463:TACCA:T	acceptor_gain	0.3400
3:160677466:CACCA:C	acceptor_gain	0.3300
3:160677700:T:A	acceptor_loss	0.3300
3:160677705:TATTA:T	acceptor_loss	0.3300
3:160677706:ATTAG:A	acceptor_loss	0.3300
3:160677707:TTAGC:T	acceptor_loss	0.3300
3:160677708:TAGC:T	acceptor_loss	0.3300
3:160677709:AGCCA:A	acceptor_loss	0.3300
3:160677638:G:GT	donor_gain	0.3200
3:160677697:T:A	acceptor_loss	0.3200
3:160677475:TACAA:T	acceptor_gain	0.3100
3:160677421:G:T	donor_gain	0.3000
3:160677476:ACAA:A	acceptor_gain	0.3000
3:160677706:A:AG	acceptor_gain	0.3000
3:160678197:T:TA	donor_gain	0.3000
3:160678198:A:AA	donor_gain	0.3000
3:160677474:CTACA:C	acceptor_gain	0.2900
3:160677710:GC:G	acceptor_gain	0.2900
3:160677903:TGGCG:T	acceptor_gain	0.2800

AlphaMissense

1257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:160677717:A:T	K124I	0.996
3:160677718:A:C	K124N	0.989
3:160677718:A:T	K124N	0.989
3:160677485:T:C	F47L	0.987
3:160677487:C:A	F47L	0.987
3:160677487:C:G	F47L	0.987
3:160677617:A:C	S91R	0.986
3:160677619:T:A	S91R	0.986
3:160677619:T:G	S91R	0.986
3:160677699:T:A	V118D	0.985
3:160677423:A:T	K26M	0.984
3:160677609:T:A	V88D	0.983
3:160677717:A:C	K124T	0.983
3:160677426:C:T	S27F	0.982
3:160677419:G:T	G25W	0.981
3:160677424:G:C	K26N	0.981
3:160677424:G:T	K26N	0.981
3:160677537:A:C	D64A	0.978
3:160677711:C:A	A122D	0.978
3:160677422:A:C	K26Q	0.976
3:160677536:G:C	D64H	0.976
3:160677715:C:A	N123K	0.976
3:160677715:C:G	N123K	0.976
3:160677600:T:C	L85P	0.975
3:160677702:T:A	V119D	0.975
3:160677423:A:C	K26T	0.974
3:160677597:G:A	G84E	0.974
3:160677537:A:G	D64G	0.973
3:160677716:A:G	K124E	0.973
3:160677404:G:A	G20R	0.971

dbSNP variants (sampled 300 via entrez): RS1000391861 (3:160678118 CTG>C), RS1003562444 (3:160675192 A>G), RS1003933696 (3:160677129 A>C,G), RS1004615641 (3:160678884 G>A,C), RS1005607016 (3:160675349 A>G), RS1006387056 (3:160677740 A>C,G), RS1007645867 (3:160676330 T>C), RS1007964721 (3:160676113 T>C), RS1010605111 (3:160676441 C>T), RS1013296642 (3:160677165 G>A), RS1014271016 (3:160678834 G>A), RS1014422342 (3:160675600 C>A,G), RS1014867788 (3:160675938 G>A,C), RS1015245472 (3:160678595 G>A,T), RS1016744617 (3:160676853 C>A)

Disease associations

OMIM: gene MIM:614439 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000408_5	Primary biliary cholangitis	1.000000e-06
GCST002375_1	Response to methotrexate in rheumatoid arthritis	4.000000e-07
GCST006716_3	Alcohol use disorder (total score)	2.000000e-08
GCST007094_30	Diastolic blood pressure	6.000000e-08
GCST007095_136	Systolic blood pressure	6.000000e-09
GCST007095_137	Systolic blood pressure	2.000000e-06
GCST007096_96	Pulse pressure	3.000000e-07
GCST007097_132	Pulse pressure	8.000000e-07
GCST007099_82	Systolic blood pressure	1.000000e-10
GCST010291_4	Attention deficit hyperactivity disorder	5.000000e-08
GCST010725_1	Malaria	3.000000e-09
GCST010725_57	Malaria	2.000000e-08
GCST010725_87	Malaria	3.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0009458	alcohol use disorder measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases expression, affects expression	5
Benzo(a)pyrene	decreases methylation, increases expression	3
lasiocarpine	increases expression	2
methyleugenol	increases expression	2
(+)-JQ1 compound	decreases expression	2
N-Nitrosopyrrolidine	increases expression	2
Silicon Dioxide	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
propionaldehyde	increases expression	1
beta-lapachone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
cylindrospermopsin	increases expression	1
clothianidin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Calcitriol	decreases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	1
Mustard Gas	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Zinc	increases expression, affects cotreatment	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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