AP3M1

Summary

AP3M1 (adaptor related protein complex 3 subunit mu 1, HGNC:569) is a protein-coding gene on chromosome 10q22.2, encoding AP-3 complex subunit mu-1 (Q9Y2T2). Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated.

The protein encoded by this gene is the medium subunit of AP-3, which is an adaptor-related protein complex associated with the Golgi region as well as more peripheral intracellular structures. AP-3 facilitates the budding of vesicles from the Golgi membrane, and it may directly function in protein sorting to the endosomal/lysosomal system. AP-3 is a heterotetrameric protein complex composed of two large subunits (delta and beta3), a medium subunit (mu3), and a small subunit (sigma 3). Mutations in one of the large subunits of AP-3 have been associated with the Hermansky-Pudlak syndrome, a genetic disorder characterized by defective lysosome-related organelles. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 26985 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 47 total
• GTEx eGene: eQTL in 16 tissues, sQTL in 24 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.82 (unconstrained)
• MANE Select transcript: NM_012095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:569
Approved symbol	AP3M1
Name	adaptor related protein complex 3 subunit mu 1
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185009
Ensembl biotype	protein_coding
OMIM	610366
Entrez	26985

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 27 protein_coding, 7 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000355264

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 2

ENST00000355264, ENST00000372745, ENST00000480373, ENST00000487653, ENST00000867215, ENST00000867216, ENST00000867217, ENST00000867218, ENST00000867219, ENST00000867220, ENST00000867221, ENST00000867222, ENST00000867223, ENST00000920397, ENST00000920398, ENST00000920399, ENST00000920400, ENST00000920401, ENST00000920402, ENST00000920403, ENST00000920404, ENST00000920405, ENST00000964631, ENST00000964632, ENST00000964633, ENST00000964634, ENST00000964635, ENST00000964636, ENST00000997429, ENST00000997430, ENST00000997431, ENST00000997432, ENST00001032848, ENST00001071362, ENST00001071363, ENST00001141022

RefSeq mRNA: 5 — MANE Select: NM_012095 NM_001320263, NM_001320264, NM_001320265, NM_012095, NM_207012

CCDS: CCDS7342

Canonical transcript exons

ENST00000355264 — 9 exons

Exon	Start	End
ENSE00001295813	74129907	74129992
ENSE00001297090	74136632	74136803
ENSE00001305036	74124380	74124524
ENSE00001306310	74129108	74129241
ENSE00001325096	74134027	74134164
ENSE00001328145	74126148	74126355
ENSE00001458546	74138107	74138382
ENSE00001458547	74150755	74150828
ENSE00001869618	74120255	74123910

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 96.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.9904 / max 474.9734, expressed in 1815 samples.

Highest expression (Bgee): pancreatic ductal cell, epithelial cell of pancreas, ileal mucosa, ganglionic eminence, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AP3M1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 24 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.1e-58	+0.40	10:74169175:T:C
Cells EBV-transformed lymphocytes	sqtl	1.2e-21	+2.35	10:74097531:A:C
Colon Sigmoid	eqtl	6.2e-20	-0.28	10:74145440:A:G
Muscle Skeletal	eqtl	8.3e-16	+0.25	10:74210244:G:A
Cells Cultured fibroblasts	sqtl	1.2e-15	+1.67	10:74097531:A:C
Artery Tibial	sqtl	1.6e-12	+1.27	10:74310450:GT:G
Adipose Subcutaneous	sqtl	1.2e-11	+1.24	10:74310450:GT:G
Colon Transverse	eqtl	2.0e-11	-0.23	10:74113881:C:T
Lung	sqtl	1.3e-09	-1.35	10:74310450:GT:G
Nerve Tibial	sqtl	1.4e-09	+1.21	10:74310450:GT:G
Breast Mammary Tissue	sqtl	8.2e-09	+1.25	10:74310450:GT:G
Esophagus Muscularis	sqtl	3.0e-07	-1.51	10:74129221:A:G
Thyroid	sqtl	8.0e-07	-1.17	10:74310450:GT:G
Esophagus Mucosa	sqtl	3.3e-06	-1.30	10:74097531:A:C
Skin Not Sun Exposed Suprapubic	sqtl	9.0e-06	-1.06	10:74310450:GT:G
Adipose Visceral Omentum	sqtl	9.3e-06	-1.08	10:74310450:GT:G
Artery Aorta	eqtl	1.7e-05	+0.18	10:74210244:G:A
Artery Aorta	sqtl	1.7e-05	-1.19	10:74310450:GT:G
Colon Transverse	sqtl	4.1e-05	-1.36	10:74097531:A:C
Muscle Skeletal	sqtl	5.9e-05	-0.96	10:74310450:GT:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
110126	32.8936	1815
110125	0.0968	38

Top tissues by expression

showing 100 of 254 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	96.13	gold quality
epithelial cell of pancreas	CL:0000083	95.13	gold quality
ileal mucosa	UBERON:0000331	95.05	gold quality
ganglionic eminence	UBERON:0004023	94.43	gold quality
ventricular zone	UBERON:0003053	93.98	gold quality
islet of Langerhans	UBERON:0000006	93.00	gold quality
adrenal tissue	UBERON:0018303	92.91	gold quality
smooth muscle tissue	UBERON:0001135	92.77	gold quality
cortical plate	UBERON:0005343	91.89	gold quality
rectum	UBERON:0001052	91.45	gold quality
tibialis anterior	UBERON:0001385	91.05	silver quality
esophagus squamous epithelium	UBERON:0006920	91.00	gold quality
monocyte	CL:0000576	90.33	gold quality
leukocyte	CL:0000738	90.27	gold quality
vermiform appendix	UBERON:0001154	89.92	gold quality
placenta	UBERON:0001987	89.82	gold quality
cartilage tissue	UBERON:0002418	89.34	gold quality
endothelial cell	CL:0000115	89.21	gold quality
right adrenal gland	UBERON:0001233	88.92	gold quality
stromal cell of endometrium	CL:0002255	88.91	gold quality
decidua	UBERON:0002450	88.84	gold quality
right adrenal gland cortex	UBERON:0035827	88.79	gold quality
pancreas	UBERON:0001264	88.63	gold quality
germinal epithelium of ovary	UBERON:0001304	88.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.45	gold quality
left adrenal gland	UBERON:0001234	88.44	gold quality
right coronary artery	UBERON:0001625	88.25	gold quality
gall bladder	UBERON:0002110	88.16	gold quality
adrenal gland	UBERON:0002369	88.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.13	gold quality
palpebral conjunctiva	UBERON:0001812	88.06	gold quality
secondary oocyte	CL:0000655	87.89	gold quality
endometrium	UBERON:0001295	87.87	gold quality
descending thoracic aorta	UBERON:0002345	87.83	gold quality
colonic mucosa	UBERON:0000317	87.81	gold quality
left adrenal gland cortex	UBERON:0035825	87.72	gold quality
bone marrow cell	CL:0002092	87.71	gold quality
lower esophagus	UBERON:0013473	87.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.39	gold quality
esophagus	UBERON:0001043	87.38	gold quality
esophagus mucosa	UBERON:0002469	87.34	gold quality
colonic epithelium	UBERON:0000397	87.17	gold quality
upper leg skin	UBERON:0004262	87.03	gold quality
left coronary artery	UBERON:0001626	87.00	gold quality
body of pancreas	UBERON:0001150	86.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.95	gold quality
lymph node	UBERON:0000029	86.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.83	gold quality
urinary bladder	UBERON:0001255	86.79	gold quality
adrenal cortex	UBERON:0001235	86.71	gold quality
popliteal artery	UBERON:0002250	86.58	gold quality
tibial artery	UBERON:0007610	86.57	gold quality
corpus epididymis	UBERON:0004359	86.51	gold quality
large intestine	UBERON:0000059	86.50	gold quality
colon	UBERON:0001155	86.41	gold quality
aorta	UBERON:0000947	86.36	gold quality
body of uterus	UBERON:0009853	86.34	gold quality
thoracic aorta	UBERON:0001515	86.32	gold quality
mucosa of stomach	UBERON:0001199	86.28	gold quality
skin of hip	UBERON:0001554	86.24	gold quality
left ventricle myocardium	UBERON:0006566	86.21	silver quality
parietal pleura	UBERON:0002400	86.19	gold quality
amniotic fluid	UBERON:0000173	86.18	gold quality
visceral pleura	UBERON:0002401	86.15	gold quality
ascending aorta	UBERON:0001496	86.13	gold quality
coronary artery	UBERON:0001621	86.09	gold quality
intestine	UBERON:0000160	86.04	gold quality
body of stomach	UBERON:0001161	85.88	gold quality
deltoid	UBERON:0001476	85.86	silver quality
minor salivary gland	UBERON:0001830	85.84	gold quality
uterus	UBERON:0000995	85.78	gold quality
tibia	UBERON:0000979	85.65	gold quality
female reproductive system	UBERON:0000474	85.64	gold quality
metanephros	UBERON:0000081	85.60	gold quality
transverse colon	UBERON:0001157	85.55	gold quality
oviduct epithelium	UBERON:0004804	85.51	gold quality
tonsil	UBERON:0002372	85.49	gold quality
gastrocnemius	UBERON:0001388	85.41	gold quality
vagina	UBERON:0000996	85.40	gold quality
muscle of leg	UBERON:0001383	85.33	gold quality
stomach	UBERON:0000945	85.28	gold quality
mouth mucosa	UBERON:0003729	85.27	gold quality
caecum	UBERON:0001153	85.22	gold quality
ectocervix	UBERON:0012249	85.22	gold quality
duodenum	UBERON:0002114	85.19	gold quality
adipose tissue	UBERON:0001013	85.18	gold quality
saliva-secreting gland	UBERON:0001044	85.08	gold quality
bone marrow	UBERON:0002371	85.08	gold quality
gingiva	UBERON:0001828	85.07	gold quality
heart left ventricle	UBERON:0002084	85.04	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.04	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.97	gold quality
blood	UBERON:0000178	84.94	gold quality
omental fat pad	UBERON:0010414	84.87	gold quality
peritoneum	UBERON:0002358	84.84	gold quality
trabecular bone tissue	UBERON:0002483	84.84	gold quality
ovary	UBERON:0000992	84.82	gold quality
cardiac ventricle	UBERON:0002082	84.80	gold quality
fallopian tube	UBERON:0003889	84.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.07

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	56.4
Frontal cortex	tissue	48.6
Corpus callosum	tissue	48.5
Spinal cord	tissue	48.0
Medulla oblongata	tissue	42.1
Substantia nigra	tissue	40.4
Pons	tissue	38.3
Midbrain	tissue	38.0
Superior colliculi	tissue	37.1
Periaqueductal gray	tissue	35.6
Hypothalamus	tissue	35.5
Thalamus	tissue	35.0
Parathyroid gland	tissue	33.8	low
Septum	tissue	32.3
Tonsil	tissue	30.7	medium
Putamen	tissue	30.6
Placenta	tissue	30.5	high
Hippocampal formation	tissue	29.6
Ventral forebrain	tissue	29.6
Cerebellum	tissue	28.7	not detected
Thymus	tissue	28.5
Olfactory bulb	tissue	28.4
Cerebral cortex	tissue	27.4	low
Occipital cortex	tissue	27.4
Smooth muscle	tissue	27.1	not detected
Locus coeruleus	tissue	27.1
Temporal cortex	tissue	26.0
Motor cortex	tissue	25.9
Rectum	tissue	25.8	medium
Entorhinal cortex	tissue	25.8
Liver	tissue	25.4	low
Retrosplenial and cingulate cortex	tissue	25.4
Retrosplenial cortex	tissue	25.3
Prefrontal cortex	tissue	25.1
Amygdala	tissue	25.1
Somatosensory cortex	tissue	25.0
Basal ganglia	tissue	24.5	medium
Prostate	tissue	24.5	medium
Esophagus	tissue	24.0	medium
Urinary bladder	tissue	24.0	medium
Lymph node	tissue	23.9	low
Insular cortex	tissue	23.7
Choroid plexus	tissue	23.4
Adipose tissue	tissue	23.1	medium
Thyroid gland	tissue	22.9	medium
Pancreas	tissue	22.7	medium
Adrenal gland	tissue	22.0	high
Endometrium 1	tissue	21.7	low
Appendix	tissue	21.4	medium
Seminal vesicle	tissue	21.3	medium
Breast	tissue	21.0	medium
Spleen	tissue	20.5	not detected
Colon	tissue	20.4	medium
Heart muscle	tissue	20.2	medium
Cervix	tissue	20.0	medium
Duodenum	tissue	19.5	medium
Postcentral gyrus	tissue	19.4
Stomach 1	tissue	19.3	medium
Tongue	tissue	19.2
Hippocampus	tissue	19.0	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (48.5), Ventral spinal cord (48.0), Dorsal spinal cord (44.9), Median raphe nucleus (30.4), Dorsal hippocampus (29.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting AP3M1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 139 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486

Functional genomics

gnomAD constraint: pLI 0.000175, LOEUF 0.823, missense Z 1.65 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000355264 — one region, missense o/e 0.82.

Literature-anchored findings (GeneRIF, showing 4)

• The present results suggest that AP3 complex genes might not play a major role in the pathogenesis of schizophrenia. (PMID:19481122)
• Data indicate that AP-3 facilitates PAR1 interaction with ALIX. (PMID:22833563)
• results demonstrate that the intact and stable AP-3 complex is required for HIV-1 assembly and release, and the involvement of the AP-3 complex in late stages of the HIV-1 replication cycle is independent of clathrin-mediated endocytosis (PMID:22875976)
• Structural basis for the recognition of tyrosine-based sorting signals by the mu3A subunit of the AP-3 adaptor complex (PMID:23404500)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ap3m1	ENSDARG00000029928
mus_musculus	Ap3m1	ENSMUSG00000021824
rattus_norvegicus	Ap3m1	ENSRNOG00000011461
caenorhabditis_elegans		WBGENE00000164

Paralogs (7): AP3M2 (ENSG00000070718), AP1M1 (ENSG00000072958), AP1M2 (ENSG00000129354), STON2 (ENSG00000140022), AP2M1 (ENSG00000161203), AP4M1 (ENSG00000221838), STON1 (ENSG00000243244)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R478	100.0%	Diamond
Bos taurus	Q24K11	99.8%	Diamond
Gallus gallus	Q5ZMP7	95.5%	Diamond
Diplobatis ommata	P47795	82.5%	Diamond
Dictyostelium discoideum	Q9GPF1	52.2%	Diamond
Arabidopsis thaliana	F4I562	44.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ADK	protein-coding	132
VCL	protein-coding	7414
C10orf55	ncRNA	414236
PLAU	protein-coding	5328
ADK-AS1	ncRNA	102723439

Protein

Protein identifiers

AP-3 complex subunit mu-1 — Q9Y2T2 (reviewed: Q9Y2T2)

Alternative names: AP-3 adaptor complex mu3A subunit, Adaptor-related protein complex 3 subunit mu-1, Mu-adaptin 3A, Mu3A-adaptin

All UniProt accessions (1): Q9Y2T2

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. (Microbial infection) Interacts with human respiratory virus (HRSV) matrix protein; this interaction plays an essential role in trafficking the matrix protein in host cells.

Subcellular location. Golgi apparatus. Cytoplasmic vesicle membrane.

Similarity. Belongs to the adaptor complexes medium subunit family.

RefSeq proteins (5): NP_001307192, NP_001307193, NP_001307194, NP_036227, NP_996895 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001392	Clathrin_mu	Family
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR018240	Clathrin_mu_CS	Conserved_site
IPR022775	AP_mu_sigma_su	Domain
IPR028565	MHD	Domain
IPR036168	AP2_Mu_C_sf	Homologous_superfamily
IPR050431	Adaptor_comp_med_subunit	Family

Pfam: PF00928, PF01217

UniProt features (4 total): sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
9C5C	Structure of Human Adaptor Protein Complex AP-3 in the Apo State	ELECTRON MICROSCOPY	3.6
9C5A	AP-3 Arf1 dimeric interface, focused refinement	ELECTRON MICROSCOPY	4.2
9C59	Human AP-3 dimer bound to myristoylated Arf1 (Q71L) and LAMP1 cargo on a lipid nanodisc	ELECTRON MICROSCOPY	4.3
9C5B	AP-3 bound to myristoylated Arf1 (Q71L) and LAMPI on a lipid nanodisc; combined map	ELECTRON MICROSCOPY	4.5
9C58	AP-3 bound to myristoylated Arf1 (Q71L)	ELECTRON MICROSCOPY	4.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2T2-F1	92.18	0.81

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis	electronic
R-HSA-390466	Chaperonin-mediated protein folding	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-391251	Protein folding	—

MSigDB gene sets: 211 (showing top): RNGTGGGC_UNKNOWN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_CELLULAR_PIGMENTATION, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME

GO Biological Process (12): protein targeting to lysosome (GO:0006622), Golgi to vacuole transport (GO:0006896), endocytosis (GO:0006897), anterograde axonal transport (GO:0008089), vesicle-mediated transport (GO:0016192), clathrin-coated vesicle cargo loading, AP-3-mediated (GO:0035654), anterograde synaptic vesicle transport (GO:0048490), platelet dense granule organization (GO:0060155), postsynaptic neurotransmitter receptor internalization (GO:0098884), melanosome assembly (GO:1903232), intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (4): small GTPase binding (GO:0031267), clathrin-cargo adaptor activity (GO:0035615), protein binding (GO:0005515), AP-3 adaptor complex binding (GO:0035651)

GO Cellular Component (13): lysosome (GO:0005764), lysosomal membrane (GO:0005765), early endosome (GO:0005769), trans-Golgi network (GO:0005802), AP-1 adaptor complex (GO:0030121), postsynaptic recycling endosome (GO:0098837), axon cytoplasm (GO:1904115), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), AP-3 adaptor complex (GO:0030123), clathrin adaptor complex (GO:0030131), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Chaperonin-mediated protein folding	1
Protein folding	1
Metabolism of proteins	1

GO top-level categories

53 GO namespaces:

Category	Terms
transport	2
intracellular protein localization	2
cytoplasm	2
AP-type membrane coat adaptor complex	2
protein targeting to vacuole	1
lysosomal transport	1
protein localization to lysosome	1
post-Golgi vesicle-mediated transport	1
vacuolar transport	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
axonal transport	1
axon cytoplasm	1
cellular process	1
clathrin-coated vesicle cargo loading	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
secretory granule organization	1
vesicle-mediated transport in synapse	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
neurotransmitter receptor internalization	1
postsynaptic endocytosis	1
melanosome organization	1
organelle assembly	1
protein transport	1
intracellular transport	1
establishment of protein localization	1
GTPase binding	1
clathrin binding	1
cargo adaptor activity	1
binding	1
protein-containing complex binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endosome	1
Golgi apparatus subcompartment	1
clathrin coat of trans-Golgi network vesicle	1
clathrin adaptor complex	1
recycling endosome	1
postsynapse	1
postsynaptic endosome	1
axon	1
neuron projection cytoplasm	1
intracellular anatomical structure	1
cellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
clathrin coat	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
lysosomal membrane	CC	high-throughput assay
small GTPase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,108 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP3M1	AP3S1	Q92572	918
AP3M1	AP3D1	O14617	896
AP3M1	AP3B1	O00203	791
AP3M1	AP3S2	P59780	705
AP3M1	AP1G1	O43747	676
AP3M1	AP2A1	O95782	674
AP3M1	HOOK1	Q9UJC3	606
AP3M1	GSTM1	P09488	605
AP3M1	KCNIP3	Q9Y2W7	552
AP3M1	SLC30A3	Q99726	519
AP3M1	CLN3	Q13286	510
AP3M1	DUSP13B	Q9UII6	471
AP3M1	COPB1	P53618	458
AP3M1	PSD4	Q8NDX1	455
AP3M1	AP1S2	P56377	440

IntAct

Human interaction partners of AP3M1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
RSPH14	physical association	0.830	10
CRMP1	physical association	0.720	6
SIPA1L2	physical association	0.720	6
SLC12A4	physical association	0.670	3
AP3B1	association	0.640	4
AGTRAP	physical association	0.560	6
ARNT2	physical association	0.560	3
DVL3	physical association	0.560	3
HTT	physical association	0.560	3
IL36RN	physical association	0.560	3
SPAG16	physical association	0.560	3
TRIM23	physical association	0.560	3
TRIM9	physical association	0.560	3
HLA-DMB	physical association	0.560	1
FRMD6	physical association	0.500	1

BioGRID (226 interactions; top human partners by supporting records): AP3D1 (Affinity Capture-Western; 7 records), AP3B1 (Co-fractionation; 5 records), AP3S1 (Affinity Capture-MS; 4 records), RSPH14 (Two-hybrid; 4 records), AGO3 (Affinity Capture-MS; 3 records), AP3B2 (Affinity Capture-MS; 3 records), AP3M2 (Affinity Capture-MS; 3 records), AP3S2 (Affinity Capture-MS; 3 records), DTNBP1 (Affinity Capture-MS; 3 records), EDA (Affinity Capture-MS; 3 records), HLA-DMB (Affinity Capture-MS; 3 records), PALM2 (Affinity Capture-MS; 3 records), RABL6 (Affinity Capture-MS; 3 records), VTI1B (Affinity Capture-MS; 3 records), AGTRAP (Two-hybrid; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
AP3M1	“form complex”	“AP-3 complex”	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
AP3-BLOC1 complex	12	AP3S1, BLOC1S2, BLOC1S4, BLOC1S5, DTNBP1, SNAPIN, AP3B1, AP3D1, AP3M1, BLOC1S1, BLOC1S3, BLOC1S6
AP3 adaptor complex	7	AP3M2, AP3S1, AP3S2, AP3B1, AP3B2, AP3D1, AP3M1

Disease & clinical

Genetic variants

Variant evidence for AP3M1: 47 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 965):

Position(s)	Effect	Δscore	Sites
10:74123911–74123912	acceptor_loss	1.0000	4
10:74124378–74124379	donor_loss	1.0000	3
10:74124525–74124526	acceptor_gain	1.0000	2
10:74124525–74124526	acceptor_loss	1.0000	3
10:74124536	acceptor_gain	1.0000
10:74129906	donor_loss	1.0000
10:74129993	acceptor_gain	1.0000
10:74129993–74129994	acceptor_loss	1.0000	5
10:74136630–74136631	donor_loss	1.0000	4
10:74136804–74136805	acceptor_loss	1.0000	3

AlphaMissense

1,369 missense substitutions predicted likely pathogenic (of 2,764 scored), across 352 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D118	8	0.988	0.995
H234	8	0.984	0.998
F250	8	0.983	0.998
D254	8	0.981	0.996
D182	8	0.974	0.992
F402	8	0.960	0.999
D217	8	0.958	0.994
N177	8	0.956	0.999
H19	8	0.907	0.961
F233	8	0.906	0.992
F82	8	0.902	0.993
D230	8	0.899	0.967
F181	8	0.897	0.997
F222	8	0.894	0.996
F257	8	0.889	0.991
D393	8	0.880	0.980
M116	8	0.855	0.994
F94	8	0.785	0.928
W167	7	0.999	1.000
E185	7	0.995	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.73e-05
Glioblastoma Multiforme (validation)	favorable	0.000327

Disease associations

OMIM: gene MIM:610366 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST002031_4	Primary tooth development (number of teeth)	8e-16
GCST010002_93	Refractive error	2e-9
GCST008309_7	Cardiac troponin-I levels	3e-9
GCST002030_4	Primary tooth development (time to first tooth eruption)	2e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0010071	cardiac troponin I measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067319 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.49	Kd	3238	nM	CHEMBL5653589
5.49	ED50	3238	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147870: Binding affinity to human AP3M1 incubated for 45 mins by Kinobead based pull down assay	kd	3.2383	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, affects expression	3
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
tetrabromobisphenol A	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Copper	decreases expression, affects binding	1
Diethylstilbestrol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1
Ketoconazole	decreases expression	1
Lead	affects expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650912	Binding	Binding affinity to human AP3M1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AP3M1 across ~30M SureChEMBL compounds — explore on Sugi Predict.