AP3D1

Summary

AP3D1 (adaptor related protein complex 3 subunit delta 1, HGNC:568) is a protein-coding gene on chromosome 19p13.3, encoding AP-3 complex subunit delta-1 (O14617). Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated.

The protein encoded by this gene is a subunit of the AP3 adaptor-like complex, which is not clathrin-associated, but is associated with the golgi region, as well as more peripheral structures. The AP-3 complex facilitates the budding of vesicles from the golgi membrane, and may be directly involved in trafficking to lysosomes. This subunit is implicated in intracellular biogenesis and trafficking of pigment granules, and possibly platelet dense granules and neurotransmitter vesicles. Defects in this gene are a cause of a new type of Hermansky-Pudlak syndrome.

Source: NCBI Gene 8943 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 10 (Strong, GenCC)
• GWAS associations: 23
• Clinical variants (ClinVar): 1,526 total — 1 pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• MANE Select transcript: NM_001261826

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:568
Approved symbol	AP3D1
Name	adaptor related protein complex 3 subunit delta 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ADTD
Ensembl gene	ENSG00000065000
Ensembl biotype	protein_coding
OMIM	607246
Entrez	8943

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 21 protein_coding, 11 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000345016, ENST00000585652, ENST00000586177, ENST00000586370, ENST00000589223, ENST00000589369, ENST00000590683, ENST00000591284, ENST00000591631, ENST00000591650, ENST00000592488, ENST00000643010, ENST00000643116, ENST00000699940, ENST00000699941, ENST00000699942, ENST00000699943, ENST00000699944, ENST00000699945, ENST00000700387, ENST00000873633, ENST00000873634, ENST00000873635, ENST00000920150, ENST00000920151, ENST00000920152, ENST00000920153, ENST00000920154, ENST00000920155, ENST00000920156, ENST00000920157, ENST00000920158, ENST00000920159, ENST00000920160, ENST00000964681

RefSeq mRNA: 3 — MANE Select: NM_001261826 NM_001261826, NM_001374799, NM_003938

CCDS: CCDS42459, CCDS58638, CCDS92482

Canonical transcript exons

ENST00000643116 — 32 exons

Exon	Start	End
ENSE00000514372	2130408	2130537
ENSE00000655415	2132471	2132578
ENSE00000655419	2127152	2127201
ENSE00000655433	2115219	2115418
ENSE00000655436	2114125	2114302
ENSE00000892365	2114748	2114821
ENSE00000892369	2116605	2116746
ENSE00000892371	2118601	2118832
ENSE00000892372	2120862	2121092
ENSE00001150801	2129318	2129457
ENSE00001150847	2111285	2111332
ENSE00001150852	2111679	2111828
ENSE00001369884	2113336	2113413
ENSE00001534514	2112860	2112967
ENSE00003491556	2123358	2123406
ENSE00003526391	2137727	2137807
ENSE00003528793	2110136	2110224
ENSE00003552612	2123830	2123879
ENSE00003554308	2138619	2138714
ENSE00003566180	2116207	2116278
ENSE00003592880	2115538	2115613
ENSE00003599653	2109873	2109958
ENSE00003619585	2121734	2121879
ENSE00003635890	2121163	2121311
ENSE00003643256	2108687	2108766
ENSE00003665446	2109086	2109207
ENSE00003667471	2110707	2110896
ENSE00003669242	2117222	2117367
ENSE00003694224	2137011	2137091
ENSE00003718906	2129090	2129163
ENSE00003831151	2151239	2151566
ENSE00003901340	2100988	2102268

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.3976 / max 384.2010, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178137	60.9353	1823
178133	0.2838	91
208636	0.1785	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.43	gold quality
adenohypophysis	UBERON:0002196	97.82	gold quality
pituitary gland	UBERON:0000007	97.78	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.78	gold quality
parotid gland	UBERON:0001831	97.69	gold quality
type B pancreatic cell	CL:0000169	97.57	gold quality
cerebellar vermis	UBERON:0004720	97.43	gold quality
stromal cell of endometrium	CL:0002255	97.42	gold quality
pylorus	UBERON:0001166	97.21	gold quality
substantia nigra pars compacta	UBERON:0001965	96.99	gold quality
frontal pole	UBERON:0002795	96.99	gold quality
paraflocculus	UBERON:0005351	96.74	gold quality
sural nerve	UBERON:0015488	96.74	gold quality
pancreatic ductal cell	CL:0002079	96.69	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.65	gold quality
middle temporal gyrus	UBERON:0002771	96.62	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.58	gold quality
body of pancreas	UBERON:0001150	96.56	gold quality
amniotic fluid	UBERON:0000173	96.54	gold quality
renal medulla	UBERON:0000362	96.46	gold quality
cerebellar hemisphere	UBERON:0002245	96.43	gold quality
cerebellar cortex	UBERON:0002129	96.42	gold quality
cerebellum	UBERON:0002037	96.40	gold quality
cardia of stomach	UBERON:0001162	96.37	gold quality
pigmented layer of retina	UBERON:0001782	96.31	gold quality
islet of Langerhans	UBERON:0000006	96.27	gold quality
pancreas	UBERON:0001264	96.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.15	gold quality
mucosa of transverse colon	UBERON:0004991	96.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	611.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting AP3D1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6817-3P	99.79	68.35	2126

Literature-anchored findings (GeneRIF, showing 9)

• The matrix region of HIV-1 Gag interacts directly with the delta subunit of the AP-3 complex, and that this interaction plays an important functional role in particle assembly (PMID:15766529)
• AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies (PMID:16162817)
• The studies demonstrate a role for AP-3 in HIV replication in a tetraspanin-rich compartment in dendritic cells (DC) and contribute to the elucidation of the trafficking pathways required for DC-T cell transfer of HIV-1 infection. (PMID:18034776)
• Unexpectedly, no evidence of binding between the N-terminal matrix (MA) domain of HIV-1 Gag and the cellular Adaptor Protein AP-3 (AP-3delta) was observed in these in vitro experiments. (PMID:22705971)
• A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese (PMID:24916648)
• We further demonstrated an abnormal storage pathway in the platelets. The current study represents a second confirmation report and implicates AP3D1 mutations as a cause of Hermansky-Pudlak Syndrome type 10. (PMID:30472485)
• A BLOC-1-AP-3 super-complex sorts a cis-SNARE complex into endosome-derived tubular transport carriers. (PMID:33886957)
• Connecting COPD GWAS Genes: FAM13A Controls TGFbeta2 Secretion by Modulating AP-3 Transport. (PMID:34166600)
• A homozygous AP3D1 missense variant in patients with sensorineural hearing loss as the leading manifestation. (PMID:36445457)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ap3d1	ENSDARG00000071424
mus_musculus	Ap3d1	ENSMUSG00000020198
rattus_norvegicus	Ap3d1	ENSRNOG00000018977
drosophila_melanogaster	g	FBGN0001087
caenorhabditis_elegans		WBGENE00000162

Protein

Protein identifiers

AP-3 complex subunit delta-1 — O14617 (reviewed: O14617)

Alternative names: AP-3 complex subunit delta, Adaptor-related protein complex 3 subunit delta-1, Delta-adaptin

All UniProt accessions (7): O14617, A0A087WYN6, A0A2R8Y4J3, A0A2R8YCY8, A0A8V8TQW4, K7ELX8, K7ERW8

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. Involved in process of CD8+ T-cell and NK cell degranulation. 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. AP-3 associates with the BLOC-1 complex. 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 SLC30A2. Interacts with CLN3 (via dileucine motif); this interaction facilitates lysosomal targeting.

Subcellular location. Cytoplasm. Golgi apparatus membrane.

Tissue specificity. Present in all adult tissues examined with the highest levels in skeletal muscle, heart, pancreas and testis.

Disease relevance. Hermansky-Pudlak syndrome 10 (HPS10) [MIM:617050] A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. HPS10 patients manifest albinism, neutropenia, immunodeficiency, neurodevelopmental delay, generalized seizures, and impaired hearing. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the adaptor complexes large subunit family.

Isoforms (5)

UniProt ID	Names	Canonical?
O14617-1	1	yes
O14617-2	2
O14617-3	3
O14617-4	4
O14617-5	5

RefSeq proteins (3): NP_001248755, NP_001361728, NP_003929 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002553	Clathrin/coatomer_adapt-like_N	Domain
IPR010474	AP3D_dom_metazoa	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017105	AP3_complex_dsu	Family
IPR058898	Mu_AP3	Domain

Pfam: PF01602, PF06375, PF26171

UniProt features (53 total): modified residue 15, repeat 11, compositionally biased region 7, splice variant 5, sequence conflict 4, coiled-coil region 3, region of interest 2, sequence variant 2, strand 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4AFI	X-RAY DIFFRACTION	2.8
9C5C	ELECTRON MICROSCOPY	3.6
9C59	ELECTRON MICROSCOPY	4.3
9C5B	ELECTRON MICROSCOPY	4.5
9C58	ELECTRON MICROSCOPY	4.7
9RTW	ELECTRON MICROSCOPY	7.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14617-F1	76.45	0.48

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 (15): 2, 632, 634, 636, 658, 688, 758, 759, 762, 764, 788, 829, 785, 828, 931

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 402 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, RORA1_01, GOCC_VACUOLAR_MEMBRANE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION

GO Biological Process (27): protein targeting to vacuole (GO:0006623), intracellular protein transport (GO:0006886), Golgi to vacuole transport (GO:0006896), anterograde axonal transport (GO:0008089), synaptic vesicle budding from endosome (GO:0016182), synaptic vesicle coating (GO:0016183), vesicle-mediated transport (GO:0016192), melanosome organization (GO:0032438), endosome to melanosome transport (GO:0035646), clathrin-coated vesicle cargo loading, AP-3-mediated (GO:0035654), synaptic vesicle recycling (GO:0036465), positive regulation of transcription by RNA polymerase II (GO:0045944), antigen processing and presentation, exogenous lipid antigen via MHC class Ib (GO:0048007), anterograde synaptic vesicle transport (GO:0048490), synaptic vesicle membrane organization (GO:0048499), positive regulation of NK T cell differentiation (GO:0051138), platelet dense granule organization (GO:0060155), protein localization to membrane (GO:0072657), neurotransmitter receptor transport, postsynaptic endosome to lysosome (GO:0098943), zinc ion import into lysosome (GO:0140916), melanosome assembly (GO:1903232), protein targeting (GO:0006605), lysosomal transport (GO:0007041), protein transport (GO:0015031), vesicle organization (GO:0016050), antigen processing and presentation (GO:0019882), vesicle-mediated transport in synapse (GO:0099003)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (17): Golgi membrane (GO:0000139), lysosomal membrane (GO:0005765), early endosome (GO:0005769), Golgi apparatus (GO:0005794), endosome membrane (GO:0010008), membrane (GO:0016020), AP-3 adaptor complex (GO:0030123), terminal bouton (GO:0043195), postsynapse (GO:0098794), presynaptic endosome (GO:0098830), glutamatergic synapse (GO:0098978), axon cytoplasm (GO:1904115), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane coat (GO:0030117), axon (GO:0030424), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
endosome	3
synapse	3
intracellular protein transport	2
vacuolar transport	2
establishment of protein localization to vacuole	2
intracellular protein localization	2
intracellular transport	2
intercellular transport	2
transport	2
bounding membrane of organelle	2
cytoplasm	2
presynapse	2
protein targeting	1
protein localization to vacuole	1
protein transport	1
post-Golgi vesicle-mediated transport	1
axonal transport	1
axon cytoplasm	1
synaptic vesicle recycling via endosome	1
synaptic vesicle budding	1
vesicle-mediated transport in synapse	1
vesicle coat assembly	1
synaptic vesicle budding from presynaptic endocytic zone membrane	1
cellular process	1
pigment granule organization	1
endosome to pigment granule transport	1
clathrin-coated vesicle cargo loading	1
establishment of localization in cell	1
synaptic vesicle cycle	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
antigen processing and presentation of exogenous antigen	1
antigen processing and presentation of lipid antigen via MHC class Ib	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
endomembrane system organization	1
membrane organization	1
NK T cell differentiation	1

Protein interactions and networks

STRING

1714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP3D1	AP3S2	P59780	962
AP3D1	AP3S1	Q92572	960
AP3D1	AP3M1	Q9Y2T2	948
AP3D1	AP3B1	O00203	929
AP3D1	AP3M2	P53677	839
AP3D1	SLC30A3	Q99726	792
AP3D1	HPS3	Q969F9	727
AP3D1	HPS5	Q9UPZ3	706
AP3D1	HPS6	Q86YV9	683
AP3D1	AP4B1	Q9Y6B7	667
AP3D1	AP4M1	O00189	658
AP3D1	AP3B2	Q13367	644
AP3D1	VAMP7	P51809	609
AP3D1	BLOC1S6	Q9UL45	601
AP3D1	AP4S1	Q9Y587	584

IntAct

142 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
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
AP3S1	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
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
WDR55	PES1	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
WDR55	AP3D1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (252): AP3D1 (Reconstituted Complex), AP3B2 (Affinity Capture-Western), AP3S1 (Affinity Capture-Western), AP3M1 (Affinity Capture-Western), RUFY1 (Affinity Capture-Western), AP3D1 (Affinity Capture-MS), AP3D1 (Affinity Capture-MS), AP3D1 (Affinity Capture-MS), AP3D1 (Affinity Capture-MS), AP3D1 (Affinity Capture-MS), AP3D1 (Co-fractionation), AP3D1 (Co-fractionation), AP3S1 (Co-fractionation), CDC73 (Co-fractionation), COPG1 (Co-fractionation)

ESM2 similar proteins: A0JMA8, A1XD93, A1XD94, A1XD95, A1XD97, A4UMC5, A4UMC6, B3DJT0, B5DFC8, E7EXT2, E7F187, F1M3L7, F7AEX0, O14617, O54774, P52590, P53569, P57740, P78344, P79398, Q06AK6, Q0IIX9, Q12929, Q17784, Q17CQ8, Q29RR5, Q2KI89, Q5R4H4, Q5R5K8, Q5R629, Q5R7J9, Q5TYV4, Q5U2Y6, Q5ZII9, Q62448, Q66J74, Q6DI35, Q865S1, Q8BH74, Q8IQ05

Diamond homologs: O14617, O54774, P54362, Q08951, Q54WN0, Q755A1, Q865S1, Q9C744, Q9UTL8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AP3D1	“form complex”	“AP-3 complex”	binding
AP3D1	“form complex”	“Neuronal AP-3”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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
trans-Golgi Network Vesicle Budding	7	20.4×	1e-05
Golgi Associated Vesicle Biogenesis	8	18.4×	7e-06
Signaling by BRAF and RAF1 fusions	5	9.8×	8e-03
MAPK6/MAPK4 signaling	6	9.4×	6e-03
Hedgehog ‘on’ state	5	9.1×	9e-03
ER-Phagosome pathway	6	8.9×	6e-03
MAPK family signaling cascades	7	8.3×	4e-03
Cargo recognition for clathrin-mediated endocytosis	6	7.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	5	44.6×	3e-05
anterograde axonal transport	6	31.4×	3e-05
positive regulation of gene expression	12	4.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1526 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	665
Likely benign	678
Benign	113

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253144	NM_001261826.3(AP3D1):c.3565_3566del (p.Val1189fs)	Pathogenic

SpliceAI

5341 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2102266:ACC:A	acceptor_gain	1.0000
19:2102267:CC:C	acceptor_gain	1.0000
19:2102267:CCCTG:C	acceptor_gain	1.0000
19:2102268:CC:C	acceptor_gain	1.0000
19:2102269:C:CC	acceptor_gain	1.0000
19:2102271:G:C	acceptor_gain	1.0000
19:2108681:GCTCA:G	donor_loss	1.0000
19:2108682:CTCA:C	donor_loss	1.0000
19:2108683:TCAC:T	donor_loss	1.0000
19:2108684:CAC:C	donor_loss	1.0000
19:2108686:C:G	donor_loss	1.0000
19:2108762:CACAA:C	acceptor_gain	1.0000
19:2108763:ACAA:A	acceptor_gain	1.0000
19:2108764:CAA:C	acceptor_gain	1.0000
19:2108764:CAAC:C	acceptor_gain	1.0000
19:2108765:AA:A	acceptor_gain	1.0000
19:2108765:AACTG:A	acceptor_loss	1.0000
19:2108767:C:CC	acceptor_gain	1.0000
19:2109080:CCTTA:C	donor_loss	1.0000
19:2109082:TTA:T	donor_loss	1.0000
19:2109083:TA:T	donor_loss	1.0000
19:2109084:A:AT	donor_loss	1.0000
19:2109085:C:CG	donor_loss	1.0000
19:2109203:CGTCA:C	acceptor_gain	1.0000
19:2109206:CA:C	acceptor_gain	1.0000
19:2109208:C:CC	acceptor_gain	1.0000
19:2109954:TCATT:T	acceptor_gain	1.0000
19:2109955:CATTC:C	acceptor_gain	1.0000
19:2109957:TT:T	acceptor_gain	1.0000
19:2109959:C:CC	acceptor_gain	1.0000

AlphaMissense

8049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2117237:A:T	V615D	1.000
19:2117245:C:A	Q612H	1.000
19:2117245:C:G	Q612H	1.000
19:2117249:G:T	A611D	1.000
19:2117261:A:T	V607E	1.000
19:2121164:A:G	W417R	1.000
19:2121164:A:T	W417R	1.000
19:2121168:G:C	F415L	1.000
19:2121168:G:T	F415L	1.000
19:2121170:A:G	F415L	1.000
19:2121201:G:C	C404W	1.000
19:2121226:A:G	L396P	1.000
19:2121274:A:G	L380P	1.000
19:2121744:A:G	L364P	1.000
19:2121747:A:G	L363P	1.000
19:2121753:A:G	L361P	1.000
19:2121756:G:T	A360D	1.000
19:2121757:C:G	A360P	1.000
19:2121762:A:G	L358P	1.000
19:2121765:C:G	R357P	1.000
19:2121768:A:C	I356S	1.000
19:2121768:A:G	I356T	1.000
19:2121768:A:T	I356N	1.000
19:2121776:G:C	D353E	1.000
19:2121776:G:T	D353E	1.000
19:2121777:T:A	D353V	1.000
19:2121777:T:C	D353G	1.000
19:2121777:T:G	D353A	1.000
19:2121778:C:A	D353Y	1.000
19:2121778:C:G	D353H	1.000

dbSNP variants (sampled 300 via entrez): RS1000028430 (19:2120389 C>A,T), RS1000057504 (19:2148456 C>T), RS1000062358 (19:2108126 G>A), RS1000144622 (19:2136281 C>T), RS1000174986 (19:2112380 G>A), RS1000221121 (19:2103987 A>G), RS1000223000 (19:2163427 G>C), RS1000273426 (19:2104150 C>T), RS1000275190 (19:2163672 C>A,T), RS1000301672 (19:2127449 G>A), RS1000373165 (19:2127555 C>T), RS1000413707 (19:2140237 C>T), RS1000422921 (19:2140272 A>G), RS1000481162 (19:2108275 A>G), RS1000484066 (19:2104136 C>G)

Disease associations

OMIM: gene MIM:607246 | disease phenotypes: MIM:617050, MIM:608233

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 10	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 10	Moderate	AR

Mondo (4): Hermansky-Pudlak syndrome 10 (MONDO:0014885), Hermansky-Pudlak syndrome 2 (MONDO:0011997), ocular albinism (MONDO:0017304), thrombocytopenia (MONDO:0002049)

Orphanet (5): Early-onset severe Hermansky-Pudlak syndrome with hearing loss, due to AP3D1 deficiency (Orphanet:664511), Hermansky-Pudlak syndrome due to AP-3 deficiency (Orphanet:183678), Hermansky-Pudlak syndrome (Orphanet:79430), Ocular albinism (Orphanet:284804), Hermansky-Pudlak syndrome due to AP3B1 deficiency (Orphanet:664500)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000319	Smooth philtrum
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000545	Myopia
HP:0000601	Hypotelorism
HP:0000613	Photophobia
HP:0000615	Abnormal pupil morphology
HP:0000639	Nystagmus
HP:0001022	Albinism
HP:0001103	Abnormal macular morphology
HP:0001107	Ocular albinism
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001480	Freckling
HP:0001744	Splenomegaly
HP:0001875	Decreased total neutrophil count
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002104	Apnea
HP:0002188	Delayed CNS myelination
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002353	EEG abnormality

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST002475_3	Myocardial infarction	4.000000e-09
GCST004601_183	Red blood cell count	6.000000e-15
GCST004604_38	Hematocrit	1.000000e-17
GCST004615_119	Hemoglobin concentration	3.000000e-14
GCST007270_10	Systolic blood pressure	6.000000e-09
GCST007270_14	Systolic blood pressure	3.000000e-06
GCST007272_4	Pulse pressure	6.000000e-15
GCST007272_8	Pulse pressure	1.000000e-10
GCST008163_618	Height	9.000000e-06
GCST008839_379	Height	3.000000e-18
GCST012226_142	Waist circumference adjusted for body mass index	2.000000e-11
GCST012227_681	Hip circumference adjusted for BMI	3.000000e-08
GCST012227_682	Hip circumference adjusted for BMI	1.000000e-30
GCST012227_728	Hip circumference adjusted for BMI	6.000000e-09
GCST012227_729	Hip circumference adjusted for BMI	9.000000e-17
GCST90002383_95	Hematocrit	7.000000e-49
GCST90002384_443	Hemoglobin	2.000000e-46
GCST90002393_629	Monocyte count	1.000000e-10
GCST90002403_271	Red blood cell count	1.000000e-40
GCST90020025_1478	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020027_188	Waist-hip index	3.000000e-09
GCST90020028_1637	Hip circumference adjusted for BMI	1.000000e-15
GCST90020028_1638	Hip circumference adjusted for BMI	2.000000e-20

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0005091	monocyte count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D016117	Albinism, Ocular	C11.270.040.090; C16.320.290.040.090; C16.320.565.100.102.090; C16.320.850.080.090; C17.800.621.440.102.090; C17.800.827.080.090; C18.452.648.100.102.090
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C537709	Hermansky Pudlak syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067055 (SINGLE PROTEIN)

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

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
8.23	Kd	5.84	nM	CHEMBL3752910
8.23	ED50	5.84	nM	CHEMBL3752910

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147869: Binding affinity to human AP3D1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0058	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects binding, increases reaction, decreases expression, increases abundance	5
Arsenic	affects expression, affects methylation, decreases expression, increases abundance, increases expression	4
methylmercuric chloride	affects cotreatment, increases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol S	increases expression, increases methylation	2
Acetaminophen	increases expression, decreases expression	2
Air Pollutants	affects expression, affects cotreatment, increases abundance, increases oxidation	2
Benzo(a)pyrene	affects methylation	2
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
lead acetate	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
ceric oxide	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	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
CHEMBL5650911	Binding	Binding affinity to human AP3D1 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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SC80	HAP1 AP3D1 (-) 1	Cancer cell line	Male
CVCL_SC81	HAP1 AP3D1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT