AP1AR

Summary

AP1AR (adaptor related protein complex 1 associated regulatory protein, HGNC:28808) is a protein-coding gene on chromosome 4q25, encoding AP-1 complex-associated regulatory protein (Q63HQ0). Necessary for adaptor protein complex 1 (AP-1)-dependent transport between the trans-Golgi network and endosomes.

Enables AP-1 adaptor complex binding activity and kinesin binding activity. Involved in negative regulation of receptor recycling and vesicle targeting, trans-Golgi to endosome. Acts upstream of or within negative regulation of substrate adhesion-dependent cell spreading. Located in Golgi apparatus and transport vesicle.

Source: NCBI Gene 55435 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_018569

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28808
Approved symbol	AP1AR
Name	adaptor related protein complex 1 associated regulatory protein
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	PRO0971, 2C18, gamma-BAR
Ensembl gene	ENSG00000138660
Ensembl biotype	protein_coding
OMIM	610851
Entrez	55435

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 retained_intron

ENST00000274000, ENST00000309703, ENST00000502954, ENST00000506522, ENST00000510527, ENST00000512741, ENST00000896479, ENST00000915678, ENST00000915679, ENST00000971023, ENST00000971024

RefSeq mRNA: 2 — MANE Select: NM_018569 NM_001128426, NM_018569

CCDS: CCDS3696, CCDS47125

Canonical transcript exons

ENST00000274000 — 10 exons

Exon	Start	End
ENSE00000970188	112266588	112266716
ENSE00000970193	112265009	112265067
ENSE00000970194	112265734	112265807
ENSE00001856704	112231787	112232174
ENSE00002051497	112268144	112273110
ENSE00003467892	112254747	112254773
ENSE00003539924	112257772	112257797
ENSE00003578996	112253208	112253256
ENSE00003654084	112262988	112263086
ENSE00003656018	112260766	112260862

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 95.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8530 / max 199.4382, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49283	19.1670	1801
49282	2.2789	1132
49284	0.4071	190

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.23	gold quality
calcaneal tendon	UBERON:0003701	93.26	gold quality
ganglionic eminence	UBERON:0004023	89.57	gold quality
jejunal mucosa	UBERON:0000399	89.50	gold quality
rectum	UBERON:0001052	88.59	gold quality
monocyte	CL:0000576	88.58	gold quality
mononuclear cell	CL:0000842	88.23	gold quality
adrenal tissue	UBERON:0018303	87.66	gold quality
leukocyte	CL:0000738	87.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.44	gold quality
ventricular zone	UBERON:0003053	87.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.89	gold quality
stromal cell of endometrium	CL:0002255	86.78	gold quality
islet of Langerhans	UBERON:0000006	86.01	gold quality
left adrenal gland	UBERON:0001234	85.82	gold quality
colonic mucosa	UBERON:0000317	85.57	gold quality
gall bladder	UBERON:0002110	85.49	gold quality
left ovary	UBERON:0002119	85.38	gold quality
left adrenal gland cortex	UBERON:0035825	85.25	gold quality
duodenum	UBERON:0002114	85.21	gold quality
transverse colon	UBERON:0001157	84.85	gold quality
right ovary	UBERON:0002118	84.81	gold quality
esophagus mucosa	UBERON:0002469	84.66	gold quality
adrenal gland	UBERON:0002369	84.55	gold quality
prefrontal cortex	UBERON:0000451	84.49	gold quality
right adrenal gland	UBERON:0001233	84.29	gold quality
nucleus accumbens	UBERON:0001882	84.29	gold quality
adrenal cortex	UBERON:0001235	84.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.10	gold quality
skin of abdomen	UBERON:0001416	84.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.88
E-MTAB-5061	no	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

183 targeting AP1AR, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
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-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Literature-anchored findings (GeneRIF, showing 3)

• Gadkin (gamma-BAR), a peripheral membrane protein localized to the trans-Golgi network and to endosomal vesicles, directly associates with the clathrin adaptor AP-1 and the motor protein kinesin KIF5, potentially regulating endosomal vesicle dynamics. (PMID:19706427)
• Studies unravel the molecular basis for Gadkin-mediated AP-1 recruitment to TGN/endosomal membranes and identify a novel subtype of the AP-1-binding motif. (PMID:19965873)
• conclude that a specific fraction of the AP2-derived endocytic pathway is dedicated to secretory purposes under the control of AP1 and Gadkin (PMID:21525240)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ap1ar	ENSMUSG00000074238
rattus_norvegicus	Ap1ar	ENSRNOG00000024492

Protein

Protein identifiers

AP-1 complex-associated regulatory protein — Q63HQ0 (reviewed: Q63HQ0)

Alternative names: 2c18, Adaptor-related protein complex 1-associated regulatory protein, Gamma-1-adaptin brefeldin A resistance protein, Gamma-A1-adaptin and kinesin interactor

All UniProt accessions (2): Q63HQ0, H0Y8Y4

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for adaptor protein complex 1 (AP-1)-dependent transport between the trans-Golgi network and endosomes. Regulates the membrane association of AP1G1/gamma1-adaptin, one of the subunits of the AP-1 adaptor complex. The direct interaction with AP1G1/gamma1-adaptin attenuates the release of the AP-1 complex from membranes. Regulates endosomal membrane traffic via association with AP-1 and KIF5B thus linking kinesin-based plus-end-directed microtubular transport to AP-1-dependent membrane traffic. May act as effector of AP-1 in calcium-induced endo-lysosome secretion. Inhibits Arp2/3 complex function; negatively regulates cell spreading, size and motility via intracellular sequestration of the Arp2/3 complex.

Subunit / interactions. Interacts (via coiled-coil domain) with AP1G1 (via GAE domain). Interacts with KIF5B. Associates with the Arp2/3 complex.

Subcellular location. Golgi apparatus. trans-Golgi network. Late endosome. Early endosome.

Post-translational modifications. Palmitoylated.

Isoforms (2)

UniProt ID	Names	Canonical?
Q63HQ0-1	1	yes
Q63HQ0-2	2

RefSeq proteins (2): NP_001121898, NP_061039* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031483	AP1AR	Family

Pfam: PF15745

UniProt features (21 total): mutagenesis site 5, region of interest 3, modified residue 3, sequence conflict 3, compositionally biased region 3, chain 1, splice variant 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q63HQ0-F1	66.16	0.21

Functional residue map

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

Post-translational modifications (3): 228, 29, 226

Mutagenesis-validated functional residues (5):

Position	Phenotype
4–5	loss of association with membranes, no effect on interaction with ap1g1; when associated with 9-s.
9	loss of association with membranes, no effect on interaction with ap1g1; when associated with 4-s-s-5.
210	loss of association with the arp2/3 complex and endosomal colocalization. abolishes interaction with klc2, no effect on
260	decreases interaction with ap1g1; when associated with l-264.
264	decreases interaction with ap1g1; when associated with l-260.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): chr4q25, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VESICLE_LOCALIZATION, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_SUBSTRATE_ADHESION, GOBP_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_GOLGI_TO_ENDOSOME_TRANSPORT, GOBP_REGULATION_OF_ARP2_3_COMPLEX_MEDIATED_ACTIN_NUCLEATION, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING

GO Biological Process (8): negative regulation of receptor recycling (GO:0001920), protein transport (GO:0015031), regulation of Arp2/3 complex-mediated actin nucleation (GO:0034315), substrate adhesion-dependent cell spreading (GO:0034446), obsolete vesicle targeting, trans-Golgi to endosome (GO:0048203), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), negative regulation of cell motility (GO:2000146), intracellular protein localization (GO:0008104)

GO Molecular Function (3): kinesin binding (GO:0019894), AP-1 adaptor complex binding (GO:0035650), protein binding (GO:0005515)

GO Cellular Component (6): endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), cytosol (GO:0005829), transport vesicle (GO:0030133)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
cytoplasmic vesicle	2
endosome	2
cytoplasm	2
receptor recycling	1
regulation of receptor recycling	1
negative regulation of macromolecule metabolic process	1
negative regulation of signaling	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
Arp2/3 complex-mediated actin nucleation	1
regulation of actin nucleation	1
cell-substrate adhesion	1
negative regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
negative regulation of locomotion	1
negative regulation of cellular process	1
cell motility	1
regulation of cell motility	1
macromolecule localization	1
cytoskeletal protein binding	1
protein-containing complex binding	1
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP1AR	CYP2C18	P33260	911
AP1AR	TRIM23	P36406	764
AP1AR	AP1G1	O43747	732
AP1AR	CYP2C9	P11712	641
AP1AR	PPIG	Q13427	609
AP1AR	CYP2C8	P10632	608
AP1AR	CYP2C19	P33259	593
AP1AR	RABEP1	Q15276	580
AP1AR	CYP3A4	P05184	576
AP1AR	CTSD	P07339	565
AP1AR	CYP2B6	P20813	541
AP1AR	ARPIN	Q7Z6K5	513
AP1AR	CYP1A1	P04798	507
AP1AR	CYP1A2	P05177	507
AP1AR	CYP2D6	P10635	507

IntAct

20 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AP1S2	AP1G1	psi-mi:“MI:0914”(association)	0.670
AP1S2	AP1G1	psi-mi:“MI:0914”(association)	0.660
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
MPRIP	AP1AR	psi-mi:“MI:0915”(physical association)	0.400
AP1S2	SLC43A3	psi-mi:“MI:0914”(association)	0.350
ARHGAP18	CLTB	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
STX7	SCAMP1	psi-mi:“MI:0914”(association)	0.350
AP1S3	AP1G1	psi-mi:“MI:0914”(association)	0.350
MFSD6L	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC9A8	AP1G1	psi-mi:“MI:0914”(association)	0.350
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
KCNJ2	ELAPOR2	psi-mi:“MI:2364”(proximity)	0.270
RB1	AP1AR	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (53): AP1AR (Affinity Capture-MS), AP1AR (Affinity Capture-MS), AP1AR (Affinity Capture-MS), AP1AR (Proximity Label-MS), AP1AR (Proximity Label-MS), AP1AR (Two-hybrid), MPRIP (Proximity Label-MS), AP1AR (Proximity Label-MS), AP1AR (Proximity Label-MS), AP1AR (Proximity Label-MS), AP1AR (Affinity Capture-RNA), AP1AR (Proximity Label-MS), AP1AR (Proximity Label-MS), AP1AR (Proximity Label-MS), AP1AR (Proximity Label-MS)

ESM2 similar proteins: B9DGG8, F4HV65, F4I5N6, F4J424, O22611, P53604, P93017, P98190, Q05349, Q0WL69, Q10060, Q10296, Q1G3K8, Q1PF35, Q32NP7, Q3KR53, Q3T183, Q3ZBW7, Q52KW0, Q566Z6, Q5F368, Q5HZ09, Q5R3Z9, Q5R787, Q5R9C3, Q5U2R6, Q5XII9, Q63HQ0, Q6DBU1, Q6GLU8, Q6NZP2, Q6PD31, Q7T3E8, Q7XPT0, Q8BQS4, Q8JZM2, Q8S307, Q8WWR9, Q94CK6, Q9BU68

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Lysosome Vesicle Biogenesis	5	90.6×	9e-08
Golgi Associated Vesicle Biogenesis	6	66.8×	2e-08
Clathrin-mediated endocytosis	5	23.7×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein transport	6	20.5×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1777 predictions. Top by Δscore:

Variant	Effect	Δscore
4:112232137:G:GT	donor_gain	1.0000
4:112232173:GG:G	donor_gain	1.0000
4:112232174:GG:G	donor_gain	1.0000
4:112232175:G:GA	donor_loss	1.0000
4:112232176:T:G	donor_loss	1.0000
4:112253206:A:AG	acceptor_gain	1.0000
4:112253207:G:GA	acceptor_gain	1.0000
4:112254742:TTCA:T	acceptor_loss	1.0000
4:112254744:CAGTT:C	acceptor_loss	1.0000
4:112254745:A:AG	acceptor_gain	1.0000
4:112254745:AGTT:A	acceptor_loss	1.0000
4:112254746:G:GG	acceptor_gain	1.0000
4:112254746:GTTT:G	acceptor_gain	1.0000
4:112254774:G:GG	donor_gain	1.0000
4:112260762:CTA:C	acceptor_loss	1.0000
4:112260763:TAGG:T	acceptor_loss	1.0000
4:112260764:A:AG	acceptor_gain	1.0000
4:112260764:AG:A	acceptor_gain	1.0000
4:112260764:AGG:A	acceptor_loss	1.0000
4:112260765:G:GG	acceptor_gain	1.0000
4:112260765:GG:G	acceptor_gain	1.0000
4:112260765:GGC:G	acceptor_gain	1.0000
4:112260765:GGCC:G	acceptor_gain	1.0000
4:112260765:GGCCT:G	acceptor_gain	1.0000
4:112260860:G:GT	donor_gain	1.0000
4:112260860:GAG:G	donor_gain	1.0000
4:112260860:GAGG:G	donor_loss	1.0000
4:112260863:G:GA	donor_loss	1.0000
4:112260863:G:GG	donor_gain	1.0000
4:112260864:T:G	donor_loss	1.0000

AlphaMissense

1989 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:112254747:T:C	F45L	0.999
4:112254749:T:A	F45L	0.999
4:112254749:T:G	F45L	0.999
4:112266701:T:A	W210R	0.999
4:112266701:T:C	W210R	0.999
4:112266703:G:C	W210C	0.999
4:112266703:G:T	W210C	0.999
4:112254748:T:C	F45S	0.998
4:112268278:T:A	W260R	0.998
4:112268278:T:C	W260R	0.998
4:112268280:G:C	W260C	0.998
4:112268280:G:T	W260C	0.998
4:112254748:T:G	F45C	0.996
4:112254757:T:C	L48P	0.996
4:112266696:T:C	L208P	0.996
4:112254755:T:A	N47K	0.995
4:112254755:T:G	N47K	0.995
4:112254757:T:A	L48Q	0.995
4:112263046:G:C	R114P	0.995
4:112266702:G:C	W210S	0.995
4:112268290:T:C	F264L	0.994
4:112268292:T:A	F264L	0.994
4:112268292:T:G	F264L	0.994
4:112253252:T:A	I43K	0.993
4:112260795:T:C	L72P	0.992
4:112268279:G:C	W260S	0.992
4:112263054:G:C	A117P	0.991
4:112253252:T:G	I43R	0.989
4:112263051:G:C	A116P	0.989
4:112254751:A:T	E46V	0.988

dbSNP variants (sampled 300 via entrez): RS1000002301 (4:112231757 A>C,G), RS1000151706 (4:112257014 G>T), RS1000153271 (4:112238689 A>G), RS1000182876 (4:112264830 C>A,T), RS1000194627 (4:112245119 A>G), RS1000200241 (4:112268033 C>A,G), RS1000253391 (4:112235060 G>A,C), RS1000306058 (4:112245478 A>T), RS1000357614 (4:112252506 G>T), RS1000441600 (4:112238057 G>A), RS1000460623 (4:112261339 G>A), RS1000581595 (4:112259260 C>T), RS1000837395 (4:112248609 CTT>C), RS1000852352 (4:112261048 C>G), RS1000873862 (4:112252831 C>T)

Disease associations

OMIM: gene MIM:610851 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_145	Body mass index	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
beta-lapachone	decreases expression, increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Caffeine	affects phosphorylation	1
Diuron	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	decreases expression, increases abundance	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9XK	Ubigene HeLa AP1AR KO	Cancer cell line	Female

Clinical trials (associated diseases)

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