AP3S2

Summary

AP3S2 (adaptor related protein complex 3 subunit sigma 2, HGNC:571) is a protein-coding gene on chromosome 15q26.1, encoding AP-3 complex subunit sigma-2 (P59780). Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated.

Predicted to be involved in anterograde synaptic vesicle transport and vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of AP-3 adaptor complex.

Source: NCBI Gene 10239 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_005829

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:571
Approved symbol	AP3S2
Name	adaptor related protein complex 3 subunit sigma 2
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	sigma3b
Ensembl gene	ENSG00000157823
Ensembl biotype	protein_coding
OMIM	602416
Entrez	10239

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000336418, ENST00000423566, ENST00000557999, ENST00000558011, ENST00000558186, ENST00000558806, ENST00000558926, ENST00000558999, ENST00000559162, ENST00000559601, ENST00000560184, ENST00000560251, ENST00000560771, ENST00000560940, ENST00000561410, ENST00000617003, ENST00000893723, ENST00000893724, ENST00000921388, ENST00000921389, ENST00000921390, ENST00000921391, ENST00000959446, ENST00000959447

RefSeq mRNA: 1 — MANE Select: NM_005829 NM_005829

CCDS: CCDS10357

Canonical transcript exons

ENST00000336418 — 6 exons

Exon	Start	End
ENSE00001341956	89830599	89835643
ENSE00002550861	89893881	89893994
ENSE00003468715	89871475	89871546
ENSE00003478885	89837615	89837722
ENSE00003602651	89888521	89888632
ENSE00003647396	89889049	89889140

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 94.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.7025 / max 500.9994, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151549	32.4676	1814
151548	0.2348	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	94.55	gold quality
islet of Langerhans	UBERON:0000006	94.49	gold quality
adrenal tissue	UBERON:0018303	94.26	gold quality
monocyte	CL:0000576	94.07	gold quality
mononuclear cell	CL:0000842	93.88	gold quality
leukocyte	CL:0000738	93.59	gold quality
colonic epithelium	UBERON:0000397	93.15	gold quality
muscle of leg	UBERON:0001383	92.47	gold quality
gastrocnemius	UBERON:0001388	92.41	gold quality
ventricular zone	UBERON:0003053	91.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.15	gold quality
calcaneal tendon	UBERON:0003701	91.06	gold quality
muscle organ	UBERON:0001630	90.85	gold quality
ganglionic eminence	UBERON:0004023	90.79	gold quality
smooth muscle tissue	UBERON:0001135	90.44	gold quality
gall bladder	UBERON:0002110	90.42	gold quality
pancreas	UBERON:0001264	90.05	gold quality
mucosa of transverse colon	UBERON:0004991	89.90	gold quality
corpus callosum	UBERON:0002336	89.62	gold quality
adrenal gland	UBERON:0002369	89.54	gold quality
stromal cell of endometrium	CL:0002255	89.38	gold quality
prefrontal cortex	UBERON:0000451	89.29	gold quality
right adrenal gland	UBERON:0001233	89.28	gold quality
right adrenal gland cortex	UBERON:0035827	89.15	gold quality
left adrenal gland	UBERON:0001234	88.94	gold quality
granulocyte	CL:0000094	88.91	gold quality
transverse colon	UBERON:0001157	88.63	gold quality
heart left ventricle	UBERON:0002084	88.58	gold quality
body of pancreas	UBERON:0001150	88.44	gold quality
left adrenal gland cortex	UBERON:0035825	88.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting AP3S2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1273H-5P	99.77	66.32	2471

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ap3s2	ENSDARG00000039882
mus_musculus	Ap3s2	ENSMUSG00000063801
rattus_norvegicus	Ap3s2	ENSRNOG00000043141
drosophila_melanogaster	or	FBGN0003008
caenorhabditis_elegans	aps-3	WBGENE00000165

Paralogs (6): AP2S1 (ENSG00000042753), AP4S1 (ENSG00000100478), AP1S1 (ENSG00000106367), AP1S3 (ENSG00000152056), AP3S1 (ENSG00000177879), AP1S2 (ENSG00000182287)

Protein

Protein identifiers

AP-3 complex subunit sigma-2 — P59780 (reviewed: P59780)

Alternative names: AP-3 complex subunit sigma-3B, Adaptor-related protein complex 3 subunit sigma-2, Sigma-3B-adaptin, Sigma-adaptin 3b

All UniProt accessions (7): A0A087WY05, P59780, H0YKM3, H0YLI7, H0YLX6, H0YN38, H0YNI6

UniProt curated annotations — full annotation on UniProt →

Function. Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.

Subunit / interactions. Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2). Interacts with AGAP1. AP-3 associates with the BLOC-1 complex.

Subcellular location. Golgi apparatus. Cytoplasmic vesicle membrane.

Tissue specificity. Present in all adult tissues examined.

Similarity. Belongs to the adaptor complexes small subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
P59780-1	1	yes
Q7Z6K5-2	C15orf38-AP3S2
P59780-2	3

RefSeq proteins (1): NP_005820* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000804	Clathrin_sm-chain_CS	Conserved_site
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR016635	AP_complex_ssu	Family
IPR022775	AP_mu_sigma_su	Domain
IPR027155	APS3	Family

Pfam: PF01217

UniProt features (5 total): splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59780-F1	82.92	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 193 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, GOBP_CELLULAR_PIGMENTATION, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_PIGMENTATION

GO Biological Process (11): intracellular protein transport (GO:0006886), Golgi to vacuole transport (GO:0006896), anterograde axonal transport (GO:0008089), synaptic vesicle coating (GO:0016183), vesicle-mediated transport (GO:0016192), clathrin-coated vesicle cargo loading, AP-3-mediated (GO:0035654), synaptic vesicle recycling (GO:0036465), anterograde synaptic vesicle transport (GO:0048490), platelet dense granule organization (GO:0060155), melanosome assembly (GO:1903232), protein transport (GO:0015031)

GO Molecular Function (0):

GO Cellular Component (11): early endosome (GO:0005769), Golgi apparatus (GO:0005794), synaptic vesicle (GO:0008021), AP-3 adaptor complex (GO:0030123), cytoplasmic vesicle membrane (GO:0030659), axon cytoplasm (GO:1904115), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020), membrane coat (GO:0030117), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
cytoplasm	3
cellular anatomical structure	3
intracellular protein localization	2
protein transport	1
intracellular transport	1
post-Golgi vesicle-mediated transport	1
vacuolar transport	1
intercellular transport	1
axonal transport	1
axon cytoplasm	1
vesicle coat assembly	1
synaptic vesicle budding from presynaptic endocytic zone membrane	1
cellular process	1
clathrin-coated vesicle cargo loading	1
establishment of localization in cell	1
synaptic vesicle cycle	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
secretory granule organization	1
melanosome organization	1
organelle assembly	1
establishment of protein localization	1
endosome	1
endomembrane system	1
intracellular membrane-bounded organelle	1
exocytic vesicle	1
presynapse	1
AP-type membrane coat adaptor complex	1
vesicle membrane	1
cytoplasmic vesicle	1
axon	1
neuron projection cytoplasm	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1
coated membrane	1
membrane protein complex	1
intracellular vesicle	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP3S2	AP3D1	O14617	962
AP3S2	AP3M1	Q9Y2T2	811
AP3S2	BHLHE23	Q8NDY6	700
AP3S2	HMG20A	Q9NP66	624
AP3S2	SLC30A3	Q99726	602
AP3S2	CDKN2A	P42771	592
AP3S2	GRB14	Q14449	571
AP3S2	VPS26A	O75436	550
AP3S2	AP1M1	Q9BXS5	544
AP3S2	AP3B1	O00203	539
AP3S2	AP1G1	O43747	513
AP3S2	AP1M2	Q9Y6Q5	484
AP3S2	AP2A1	O95782	481
AP3S2	ST6GAL1	P15907	479
AP3S2	STXBP5L	Q9Y2K9	474

IntAct

26 interactions, top by confidence:

A	B	Type	Score
AP3M1	AP3B1	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
AP3M2	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
E2F4	AP3S2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
RNF13	AP3D1	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
MFSD12	SNAP23	psi-mi:“MI:0914”(association)	0.350
SLC18B1	AP3D1	psi-mi:“MI:0914”(association)	0.350
SLC2A8	AP3D1	psi-mi:“MI:0914”(association)	0.350
SLC38A6	AP3D1	psi-mi:“MI:0914”(association)	0.350
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
TAF15	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
EIF3G	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (48): AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-RNA), AP3S2 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3S2 (Two-hybrid), AP3S2 (Reconstituted Complex), AP3S2 (Reconstituted Complex), ARF1 (Reconstituted Complex)

ESM2 similar proteins: A0CDD4, D3ZRP6, O22715, O23140, P35585, P35602, P35603, P35615, P48454, P53027, P53619, P59780, P62495, P62496, P62497, P62498, P84091, P84092, Q0VCX5, Q1JQA3, Q24208, Q2KJ81, Q32Q06, Q3SYW1, Q3ZC13, Q4R706, Q5NVF7, Q5R4C7, Q5RDP9, Q5U2Q7, Q5XJY5, Q5ZL57, Q5ZMP6, Q66H80, Q6NWK2, Q6P856, Q6PC69, Q7ZW98, Q801Q8, Q8BSZ2

Diamond homologs: B0G185, O23685, O50016, O82201, P35181, P47064, P53680, P56377, P59780, P61966, P61967, P62743, P62744, Q00381, Q09905, Q17QC5, Q1JQ98, Q1JQA3, Q2YDH6, Q3ZBB6, Q3ZBS3, Q4ICG5, Q4WS49, Q54H39, Q54NZ4, Q54WW3, Q553S2, Q5BFF8, Q5R940, Q5RDP9, Q75F71, Q7SAQ1, Q7TN05, Q84WL9, Q8BSZ2, Q8LEZ8, Q8VZ37, Q92572, Q96PC3, Q9DB50

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AP3S2	“form complex”	“Neuronal AP-3”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1636 predictions. Top by Δscore:

Variant	Effect	Δscore
15:89835639:CCACC:C	acceptor_gain	1.0000
15:89835640:CACC:C	acceptor_gain	1.0000
15:89835640:CACCC:C	acceptor_gain	1.0000
15:89835641:ACC:A	acceptor_gain	1.0000
15:89835642:CC:C	acceptor_gain	1.0000
15:89835642:CCC:C	acceptor_gain	1.0000
15:89835643:CC:C	acceptor_gain	1.0000
15:89835644:C:CA	acceptor_loss	1.0000
15:89835644:C:CC	acceptor_gain	1.0000
15:89835644:C:T	acceptor_gain	1.0000
15:89837486:C:CT	acceptor_gain	1.0000
15:89837487:A:T	acceptor_gain	1.0000
15:89837610:CT:C	donor_gain	1.0000
15:89837610:CTCA:C	donor_gain	1.0000
15:89837612:CA:C	donor_loss	1.0000
15:89837612:CACCT:C	donor_loss	1.0000
15:89837613:A:AC	donor_gain	1.0000
15:89837614:C:A	donor_loss	1.0000
15:89837614:C:CC	donor_gain	1.0000
15:89837614:CCT:C	donor_gain	1.0000
15:89837718:TGCAC:T	acceptor_gain	1.0000
15:89837719:GCAC:G	acceptor_gain	1.0000
15:89837720:CAC:C	acceptor_gain	1.0000
15:89837720:CACC:C	acceptor_gain	1.0000
15:89837721:AC:A	acceptor_gain	1.0000
15:89837721:ACCTA:A	acceptor_loss	1.0000
15:89837722:CC:C	acceptor_gain	1.0000
15:89837723:C:CC	acceptor_gain	1.0000
15:89837724:T:A	acceptor_loss	1.0000
15:89871470:TATA:T	donor_loss	1.0000

AlphaMissense

1282 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:89837688:C:A	G127V	1.000
15:89837689:C:A	G127W	1.000
15:89871487:G:C	F111L	1.000
15:89871487:G:T	F111L	1.000
15:89871489:A:G	F111L	1.000
15:89871497:T:A	D108V	1.000
15:89871500:A:G	L107S	1.000
15:89871502:T:A	E106D	1.000
15:89871502:T:G	E106D	1.000
15:89871503:T:A	E106V	1.000
15:89871503:T:C	E106G	1.000
15:89871504:C:T	E106K	1.000
15:89871506:C:T	C105Y	1.000
15:89871517:G:C	F101L	1.000
15:89871517:G:T	F101L	1.000
15:89871519:A:G	F101L	1.000
15:89871530:A:G	L97P	1.000
15:89888528:A:G	L89P	1.000
15:89888531:T:A	D88V	1.000
15:89888543:A:G	L84P	1.000
15:89888543:A:T	L84H	1.000
15:89888582:A:G	L71P	1.000
15:89888582:A:T	L71H	1.000
15:89888585:G:A	T70I	1.000
15:89888597:C:G	R66P	1.000
15:89837688:C:T	G127E	0.999
15:89837689:C:G	G127R	0.999
15:89837689:C:T	G127R	0.999
15:89837709:A:G	L120P	0.999
15:89871488:A:G	F111S	0.999

dbSNP variants (sampled 300 via entrez): RS1000050564 (15:89886454 T>G), RS1000141168 (15:89832450 A>G), RS1000162925 (15:89857524 C>G,T), RS1000230424 (15:89841648 C>T), RS1000238643 (15:89891387 G>A), RS1000291907 (15:89849863 G>T), RS1000418088 (15:89844354 T>A), RS1000487629 (15:89852979 G>A), RS1000498024 (15:89856043 T>C), RS1000559284 (15:89891519 C>A), RS1000632537 (15:89895913 G>A), RS1000670774 (15:89881213 G>A), RS1000679175 (15:89848993 G>A), RS1000701126 (15:89843045 C>G,T), RS1000736178 (15:89874535 G>A)

Disease associations

OMIM: gene MIM:602416 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001213_5	Type 2 diabetes	2.000000e-11
GCST002128_11	Type 2 diabetes	3.000000e-06
GCST002352_22	Type 2 diabetes	5.000000e-07
GCST004894_124	Type 2 diabetes	4.000000e-08
GCST005414_8	Type 2 diabetes	4.000000e-06
GCST006867_129	Type 2 diabetes	6.000000e-11
GCST007847_51	Type 2 diabetes	3.000000e-08
GCST009379_159	Type 2 diabetes	4.000000e-20
GCST010118_51	Type 2 diabetes	8.000000e-13
GCST011320_30	Type 2 diabetes or prostate cancer (pleiotropy)	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment, decreases expression	4
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects expression, affects reaction	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Isotretinoin	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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