AP1G1

Summary

AP1G1 (adaptor related protein complex 1 subunit gamma 1, HGNC:555) is a protein-coding gene on chromosome 16q22.2, encoding AP-1 complex subunit gamma-1 (O43747). Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes.

Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 164 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 226 total — 14 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• MANE Select transcript: NM_001128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:555
Approved symbol	AP1G1
Name	adaptor related protein complex 1 subunit gamma 1
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166747
Ensembl biotype	protein_coding
OMIM	603533
Entrez	164

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 25 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000299980, ENST00000393512, ENST00000450149, ENST00000562934, ENST00000563104, ENST00000563259, ENST00000564155, ENST00000565009, ENST00000565161, ENST00000565412, ENST00000565642, ENST00000566161, ENST00000566179, ENST00000567583, ENST00000568327, ENST00000569044, ENST00000569185, ENST00000569748, ENST00000569975, ENST00000570017, ENST00000570052, ENST00000570297, ENST00000905356, ENST00000905357, ENST00000905358, ENST00000905359, ENST00000905360, ENST00000905361, ENST00000905362, ENST00000905363, ENST00000905364, ENST00000905365, ENST00000922247, ENST00000949881, ENST00000949882, ENST00000949883

RefSeq mRNA: 2 — MANE Select: NM_001128 NM_001030007, NM_001128

CCDS: CCDS32480, CCDS45522

Canonical transcript exons

ENST00000299980 — 23 exons

Exon	Start	End
ENSE00001324792	71729000	71733159
ENSE00002292842	71774468	71774592
ENSE00002308804	71773221	71773362
ENSE00002499967	71734609	71734707
ENSE00002613572	71808763	71808834
ENSE00003482043	71745473	71745614
ENSE00003482738	71746588	71746692
ENSE00003507886	71748251	71748378
ENSE00003510560	71738942	71739102
ENSE00003519941	71745144	71745270
ENSE00003524444	71739234	71739341
ENSE00003528420	71750210	71750332
ENSE00003531716	71749894	71749983
ENSE00003546024	71764350	71764448
ENSE00003555139	71761512	71761567
ENSE00003573962	71756019	71756159
ENSE00003584196	71769623	71769699
ENSE00003613179	71753833	71753887
ENSE00003626479	71765489	71765584
ENSE00003630647	71771156	71771252
ENSE00003642107	71764646	71764726
ENSE00003642435	71789279	71789482
ENSE00003651082	71758808	71758921

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.0023 / max 765.7221, expressed in 1824 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158044	33.9878	1822
158045	19.5433	1809
158043	3.0717	1349
158042	0.9845	487
158046	0.3674	180
158034	0.0477	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.30	gold quality
calcaneal tendon	UBERON:0003701	95.78	gold quality
adrenal tissue	UBERON:0018303	95.61	gold quality
colonic epithelium	UBERON:0000397	95.00	gold quality
sperm	CL:0000019	94.84	gold quality
corpus epididymis	UBERON:0004359	94.76	gold quality
tendon	UBERON:0000043	94.57	gold quality
islet of Langerhans	UBERON:0000006	94.43	gold quality
left testis	UBERON:0004533	94.12	gold quality
sural nerve	UBERON:0015488	94.12	gold quality
middle temporal gyrus	UBERON:0002771	94.03	gold quality
right testis	UBERON:0004534	93.91	gold quality
cortical plate	UBERON:0005343	93.85	gold quality
caput epididymis	UBERON:0004358	93.75	gold quality
testis	UBERON:0000473	93.73	gold quality
secondary oocyte	CL:0000655	93.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.45	gold quality
amniotic fluid	UBERON:0000173	93.40	gold quality
esophagus squamous epithelium	UBERON:0006920	93.14	gold quality
corpus callosum	UBERON:0002336	93.07	gold quality
male germ cell	CL:0000015	92.88	gold quality
ventricular zone	UBERON:0003053	92.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.52	gold quality
medial globus pallidus	UBERON:0002477	92.38	gold quality
tonsil	UBERON:0002372	92.37	gold quality
stromal cell of endometrium	CL:0002255	92.35	gold quality
right adrenal gland cortex	UBERON:0035827	92.32	gold quality
pancreas	UBERON:0001264	92.31	gold quality
cauda epididymis	UBERON:0004360	92.27	gold quality
ganglionic eminence	UBERON:0004023	92.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

282 targeting AP1G1, 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-4262	100.00	73.26	3931
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
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-126-5P	100.00	72.71	3180
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
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-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Literature-anchored findings (GeneRIF, showing 9)

• Gamma-adaptin interacts directly with Rabaptin-5 through its ear domain.The interaction may play a role in membrane trafficking between the trans-Golgi network and endosomes. (PMID:11872161)
• crystal structure of the human gamma 1-adaptin ear domain consists solely of an immunoglobulin-like fold, unlike the alpha-adaptin ear domain (PMID:12042876)
• Gamma-adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation (PMID:16867982)
• Interaction between Rab4b and AP1gamma allows the budding of clathrin-coated vesicles for subsequent traffic to recycling endosomes. (PMID:24006255)
• Depletion of the gamma2 or mu1A (AP1M1) subunits of AP-1, but not of gamma1 (AP1G1), precludes Nef-mediated lysosomal degradation of CD4. (PMID:27909244)
• High ASCT2 expression is associated with drug resistance head and neck squamous cell carcinoma. (PMID:28823958)
• Data indicate a functional link between adaptor protein complex 1 (AP-1) and the WD repeat protein 11 (WDR11) complex. (PMID:29426865)
• De novo and bi-allelic variants in AP1G1 cause neurodevelopmental disorder with developmental delay, intellectual disability, and epilepsy. (PMID:34102099)
• Endosomal protein expression of gamma1-adaptin is associated with tumor growth activity and relapse-free survival in breast cancer. (PMID:38265632)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ap1g1	ENSDARG00000102394
mus_musculus	Ap1g1	ENSMUSG00000031731
rattus_norvegicus	Ap1g1	ENSRNOG00000069458
drosophila_melanogaster	AP-1gamma	FBGN0030089
caenorhabditis_elegans	apg-1	WBGENE00000158

Paralogs (4): AP4E1 (ENSG00000081014), AP2A2 (ENSG00000183020), AP2A1 (ENSG00000196961), AP1G2 (ENSG00000213983)

Protein

Protein identifiers

AP-1 complex subunit gamma-1 — O43747 (reviewed: O43747)

Alternative names: Adaptor protein complex AP-1 subunit gamma-1, Adaptor-related protein complex 1 subunit gamma-1, Clathrin assembly protein complex 1 gamma-1 large chain, Gamma-adaptin, Gamma1-adaptin, Golgi adaptor HA1/AP1 adaptin subunit gamma-1

All UniProt accessions (14): A0A140VJE7, B3KNW1, B4DGE1, O43747, H3BN71, H3BN75, H3BNN2, H3BNR4, H3BPN9, H3BR36, H3BRM7, H3BS13, H3BUN9, H3BV30

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. In association with AFTPH/aftiphilin in the aftiphilin/p200/gamma-synergin complex, involved in the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes.

Subunit / interactions. Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Interacts (via GAE domain) with RABEP1. Interacts with SYNRG/gamma-synergin. Interacts with EPS15. Interacts (via GAE domain) with AP1AR (via coiled-coil domain). Interacts with CLN3 (via dileucine motif); this interaction facilitates lysosomal targeting. Interacts (via GAE domain) with AFTPH/aftiphilin; the interaction is required to recruit AFTPH/aftiphilin to the perinuclear region of the cell. Interacts with PSEN2; this interaction is dependent on PSEN2 phosphorylation and directs PSEN2 from early endosomes to late endosomes/lysosomes.

Subcellular location. Golgi apparatus. Cytoplasmic vesicle. Clathrin-coated vesicle membrane. Cytoplasm. Perinuclear region. Clathrin-coated vesicle. Membrane. Clathrin-coated pit.

Tissue specificity. Widely expressed.

Disease relevance. Usmani-Riazuddin syndrome, autosomal dominant (USRISD) [MIM:619467] A neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development and speech delay, hypotonia, and behavioral abnormalities. More variable additional features may include seizures and distal limb anomalies. The disease is caused by variants affecting the gene represented in this entry. Usmani-Riazuddin syndrome, autosomal recessive (USRISR) [MIM:619548] A neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development and speech delay, hypotonia, spasticity, and behavioral abnormalities. More variable additional features may include seizures, scoliosis, and joint laxity. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the adaptor complexes large subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43747-1	1	yes
O43747-2	2

RefSeq proteins (2): NP_001025178, NP_001119* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002553	Clathrin/coatomer_adapt-like_N	Domain
IPR008152	Clathrin_a/b/g-adaptin_app_Ig	Domain
IPR008153	GAE_dom	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR013041	Clathrin_app_Ig-like_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017107	AP1_complex_gsu	Family
IPR050840	Adaptor_Complx_Large_Subunit	Family

Pfam: PF01602, PF02883

UniProt features (27 total): strand 9, sequence variant 8, sequence conflict 4, helix 2, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1IU1	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43747-F1	84.56	0.68

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-164940	Nef mediated downregulation of MHC class I complex cell surface expression
R-HSA-2132295	MHC class II antigen presentation
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-1280218	Adaptive Immune System
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-164938	Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-164952	The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-168256	Immune System
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 473 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, AAGCAAT_MIR137, TAATAAT_MIR126, GOBP_LYSOSOMAL_TRANSPORT, chr16q22, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GGGNRMNNYCAT_UNKNOWN, GOCC_VACUOLAR_MEMBRANE, TTCCGTT_MIR191, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_EXOCYTOSIS

GO Biological Process (14): intracellular protein transport (GO:0006886), Golgi to vacuole transport (GO:0006896), synaptic vesicle budding from endosome (GO:0016182), vesicle-mediated transport (GO:0016192), melanosome organization (GO:0032438), endosome to melanosome transport (GO:0035646), positive regulation of natural killer cell degranulation (GO:0043323), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), synaptic vesicle endocytosis (GO:0048488), platelet dense granule organization (GO:0060155), Golgi to lysosome transport (GO:0090160), basolateral protein secretion (GO:0110010), melanosome assembly (GO:1903232), protein transport (GO:0015031)

GO Molecular Function (6): collagen binding (GO:0005518), kinesin binding (GO:0019894), GTP-dependent protein binding (GO:0030742), small GTPase binding (GO:0031267), clathrin-cargo adaptor activity (GO:0035615), protein binding (GO:0005515)

GO Cellular Component (22): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), early endosome (GO:0005769), Golgi apparatus (GO:0005794), cytosol (GO:0005829), clathrin-coated pit (GO:0005905), membrane (GO:0016020), AP-1 adaptor complex (GO:0030121), clathrin-coated vesicle (GO:0030136), cytoplasmic vesicle membrane (GO:0030659), clathrin-coated vesicle membrane (GO:0030665), trans-Golgi network membrane (GO:0032588), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), presynapse (GO:0098793), trans-Golgi network (GO:0005802), endomembrane system (GO:0012505), membrane coat (GO:0030117), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202), intracellular vesicle (GO:0097708)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	2
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1
Adaptive Immune System	1
Immune System	1
Viral Infection Pathways	1
HIV Infection	1
The role of Nef in HIV-1 replication and disease pathogenesis	1
Host Interactions of HIV factors	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	5
intracellular protein localization	2
intracellular transport	2
transport	2
endosome	2
endomembrane system	2
protein transport	1
post-Golgi vesicle-mediated transport	1
vacuolar transport	1
intercellular transport	1
synaptic vesicle recycling via endosome	1
synaptic vesicle budding	1
vesicle-mediated transport in synapse	1
cellular process	1
pigment granule organization	1
endosome to pigment granule transport	1
positive regulation of leukocyte degranulation	1
natural killer cell degranulation	1
regulation of natural killer cell degranulation	1
positive regulation of natural killer cell mediated cytotoxicity	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
secretory granule organization	1
Golgi to vacuole transport	1
lysosomal transport	1
cytosolic transport	1
protein secretion	1
melanosome organization	1
organelle assembly	1
establishment of protein localization	1
protein-containing complex binding	1
cytoskeletal protein binding	1
protein binding	1
GTPase binding	1
clathrin binding	1

Protein interactions and networks

STRING

1766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP1G1	AP1M1	Q9BXS5	925
AP1G1	AP1S1	P61966	795
AP1G1	BBS9	P78514	769
AP1G1	BBS7	Q8IWZ6	766
AP1G1	BBS5	Q8N3I7	765
AP1G1	BBS2	Q9BXC9	761
AP1G1	BBS1	Q8NFJ9	761
AP1G1	AP1AR	Q63HQ0	732
AP1G1	BBS4	Q96RK4	719
AP1G1	RABEP1	Q15276	689
AP1G1	CLTC	Q00610	687
AP1G1	AP3S1	Q92572	681
AP1G1	AP3M1	Q9Y2T2	665
AP1G1	AP4M1	O00189	661
AP1G1	CLTCL1	P53675	650

IntAct

94 interactions, top by confidence:

A	B	Type	Score
AP1G1	AP1S2	psi-mi:“MI:0915”(physical association)	0.660
AP1S2	AP1G1	psi-mi:“MI:0914”(association)	0.660
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
AAGAB	STXBP3	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
RABEP1	AP1G1	psi-mi:“MI:0915”(physical association)	0.510
AP1G1	RABEP1	psi-mi:“MI:0915”(physical association)	0.510
AP1G1	AP1B1	psi-mi:“MI:0403”(colocalization)	0.490
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
AP1G1	PACS1	psi-mi:“MI:0407”(direct interaction)	0.440
CALY	AP3D1	psi-mi:“MI:0915”(physical association)	0.400
AKT2	AP1G1	psi-mi:“MI:0915”(physical association)	0.400
Slc2a8	AP1G1	psi-mi:“MI:0915”(physical association)	0.400
RABGEF1	AP1G1	psi-mi:“MI:0915”(physical association)	0.370
AP1G1	Ap1s2	psi-mi:“MI:0915”(physical association)	0.370
AP1G1	Ap1s1	psi-mi:“MI:0915”(physical association)	0.370
AP1S2	SLC43A3	psi-mi:“MI:0914”(association)	0.350
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRKAR1A	ADAM10	psi-mi:“MI:0914”(association)	0.350
RAB5A	EIF3CL	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (253): AP1S2 (Two-hybrid), UBL7 (Two-hybrid), CORO7 (Affinity Capture-Western), AP1G1 (Affinity Capture-Western), AP1G1 (Affinity Capture-MS), AP1G1 (Affinity Capture-MS), AP1G1 (Affinity Capture-MS), AP1G1 (Affinity Capture-MS), AP1G1 (Affinity Capture-RNA), AP1B1 (Co-fractionation), AP1G1 (Co-fractionation), AP1G1 (Co-fractionation), AP1G1 (Co-fractionation), AP1G1 (Co-fractionation), AP1G1 (Co-fractionation)

ESM2 similar proteins: A2VE21, B4MY75, D4ABY2, O00203, O43747, O81742, P22892, P45437, P53620, P56701, P87140, Q0WW26, Q13200, Q13367, Q22498, Q29AE5, Q29G21, Q32PG1, Q4AEF8, Q4FZT9, Q54HL0, Q54X82, Q5R5M2, Q5R9I6, Q66JI9, Q6DKD7, Q6XJG8, Q6Z382, Q7PVF6, Q7YRF1, Q84K16, Q8H852, Q8I0G5, Q8L5Y6, Q8L7A9, Q8VDM4, Q93VQ0, Q99128, Q9I8E6, Q9JME5

Diamond homologs: A0A0G2JV04, A3LXQ8, F4KAU9, O01498, O14964, O43747, O60784, O75843, O75886, O88512, O88746, O93436, P22892, P70297, Q0V8S0, Q5R5M2, Q68FJ8, Q6P5E6, Q8BMI3, Q8R0H9, Q92783, Q960X8, Q99LI8, Q9JJ50, Q9NZ52, Q9UJY4, Q9UJY5, O95782, P17426, Q12028, Q84K16, Q8I8U2, Q8LPK4, Q8LPL6, Q99128, Q9UU81, Q9ZUI6, O94973, P17427, P18484

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AP1G1	“form complex”	“AP-1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	6	58.6×	4e-08
The role of Nef in HIV-1 replication and disease pathogenesis	6	58.6×	4e-08
Host Interactions of HIV factors	6	31.0×	2e-06
Lysosome Vesicle Biogenesis	6	30.1×	2e-06
Golgi Associated Vesicle Biogenesis	8	24.7×	7e-08
trans-Golgi Network Vesicle Budding	6	23.4×	7e-06
Clathrin-mediated endocytosis	13	17.0×	2e-10
EPH-ephrin mediated repulsion of cells	5	16.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	5	55.4×	6e-06
synaptic vesicle endocytosis	5	27.0×	2e-04
vesicle-mediated transport	10	12.0×	3e-06
intracellular protein transport	12	9.7×	2e-06
endocytosis	7	8.3×	2e-03
protein transport	9	4.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	12
Uncertain significance	126
Likely benign	37
Benign	1

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1299368	NM_001128.6(AP1G1):c.103C>T (p.Arg35Trp)	Pathogenic
1299369	NM_001128.6(AP1G1):c.104G>A (p.Arg35Gln)	Pathogenic
1299370	NM_001128.6(AP1G1):c.728C>A (p.Pro243His)	Pathogenic
1708225	NM_001128.6(AP1G1):c.1246C>T (p.Arg416Ter)	Pathogenic
2206183	NM_001128.6(AP1G1):c.2080C>T (p.Gln694Ter)	Pathogenic
2573171	NM_001128.6(AP1G1):c.1497+1G>A	Pathogenic
3384011	NM_001128.6(AP1G1):c.515dup (p.Met172fs)	Pathogenic
3403213	NM_001128.6(AP1G1):c.1135C>T (p.Arg379Ter)	Pathogenic
3602434	NM_001128.6(AP1G1):c.436dup (p.Leu146fs)	Pathogenic
4071974	NM_001128.6(AP1G1):c.1295_1299del (p.Tyr432fs)	Pathogenic
4527877	NM_001128.6(AP1G1):c.610C>T (p.Arg204Ter)	Pathogenic
4530594	NM_001128.6(AP1G1):c.1872+1G>T	Pathogenic
4685130	NM_001128.6(AP1G1):c.77_84del (p.Met26fs)	Pathogenic
4759504	NM_001128.6(AP1G1):c.1630del (p.Ile544fs)	Pathogenic
1321989	NM_001128.6(AP1G1):c.974+1G>T	Likely pathogenic
1701295	NM_001128.6(AP1G1):c.1735_1749delinsCCC (p.Ala579_Arg583delinsPro)	Likely pathogenic
1708218	NM_001128.6(AP1G1):c.43C>T (p.Arg15Trp)	Likely pathogenic
3062338	NM_001128.6(AP1G1):c.2039del (p.Gln680fs)	Likely pathogenic
3248633	NM_001128.6(AP1G1):c.919-1G>T	Likely pathogenic
3376345	NM_001128.6(AP1G1):c.-2G>A	Likely pathogenic
3581243	NM_001128.6(AP1G1):c.868del (p.Tyr290fs)	Likely pathogenic
3602540	NM_001128.6(AP1G1):c.126C>A (p.Asp42Glu)	Likely pathogenic
4082056	NM_001128.6(AP1G1):c.468G>A (p.Lys156=)	Likely pathogenic
4795249	NM_001128.6(AP1G1):c.1678C>T (p.Gln560Ter)	Likely pathogenic
564338	GRCh37/hg19 16q22.1-22.2(chr16:70646969-72849701)x1	Likely pathogenic
564341	GRCh37/hg19 16q22.2-22.3(chr16:71561717-73724195)x1	Likely pathogenic

SpliceAI

3661 predictions. Top by Δscore:

Variant	Effect	Δscore
16:71734604:CTCA:C	donor_loss	1.0000
16:71734605:TCA:T	donor_loss	1.0000
16:71734606:CA:C	donor_loss	1.0000
16:71734607:A:AG	donor_loss	1.0000
16:71734705:TGT:T	acceptor_gain	1.0000
16:71734708:C:CC	acceptor_gain	1.0000
16:71738936:TAGTA:T	donor_loss	1.0000
16:71738938:GTA:G	donor_loss	1.0000
16:71738939:TA:T	donor_loss	1.0000
16:71738941:CCTT:C	donor_loss	1.0000
16:71739100:TGC:T	acceptor_gain	1.0000
16:71739102:CCTGA:C	acceptor_loss	1.0000
16:71739103:C:CC	acceptor_gain	1.0000
16:71739103:CT:C	acceptor_loss	1.0000
16:71745138:CCTCA:C	donor_loss	1.0000
16:71745139:CTCAC:C	donor_loss	1.0000
16:71745140:TCACC:T	donor_loss	1.0000
16:71745141:CAC:C	donor_loss	1.0000
16:71745142:A:C	donor_loss	1.0000
16:71745267:TGGCC:T	acceptor_loss	1.0000
16:71745271:C:CA	acceptor_loss	1.0000
16:71745272:T:C	acceptor_loss	1.0000
16:71746582:GCTCA:G	donor_loss	1.0000
16:71746583:CTCA:C	donor_loss	1.0000
16:71746584:TCACC:T	donor_loss	1.0000
16:71746585:CA:C	donor_loss	1.0000
16:71746586:A:AC	donor_gain	1.0000
16:71746586:A:AG	donor_loss	1.0000
16:71746587:C:CC	donor_gain	1.0000
16:71746587:C:T	donor_loss	1.0000

AlphaMissense

5381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:71733143:C:G	R795P	1.000
16:71733146:A:C	M794R	1.000
16:71734625:A:T	V784D	1.000
16:71734697:A:G	L760P	1.000
16:71738949:A:T	V754E	1.000
16:71738952:G:T	A753E	1.000
16:71738955:G:T	A752D	1.000
16:71745594:A:G	M584T	1.000
16:71745603:A:G	L581P	1.000
16:71746630:G:T	A563E	1.000
16:71746631:C:G	A563P	1.000
16:71746632:C:A	R562S	1.000
16:71746632:C:G	R562S	1.000
16:71746636:T:G	Q561P	1.000
16:71748280:C:A	K532N	1.000
16:71748280:C:G	K532N	1.000
16:71748291:C:G	A529P	1.000
16:71749949:C:T	G481D	1.000
16:71749950:C:G	G481R	1.000
16:71749959:A:G	W478R	1.000
16:71749959:A:T	W478R	1.000
16:71753868:A:G	W417R	1.000
16:71753868:A:T	W417R	1.000
16:71756082:A:G	L389P	1.000
16:71756133:A:G	L372P	1.000
16:71756133:A:T	L372Q	1.000
16:71756145:A:C	L368W	1.000
16:71756154:G:T	A365E	1.000
16:71756155:C:G	A365P	1.000
16:71758814:A:T	I361K	1.000

dbSNP variants (sampled 300 via entrez): RS1000013015 (16:71809272 G>A,T), RS1000037322 (16:71744054 C>G,T), RS1000056373 (16:71809268 G>A), RS1000058983 (16:71786428 C>T), RS1000102438 (16:71774274 A>T), RS1000108308 (16:71809390 C>A,T), RS1000143883 (16:71787229 G>C,T), RS1000161661 (16:71748933 G>A), RS1000193496 (16:71791236 A>C), RS1000200714 (16:71765127 G>C), RS1000312117 (16:71745639 T>A,C), RS1000322749 (16:71771318 A>T), RS1000355444 (16:71771047 C>A,G), RS1000376158 (16:71741458 C>T), RS1000424305 (16:71810329 G>A,C,T)

Disease associations

OMIM: gene MIM:603533 | disease phenotypes: MIM:619467, MIM:619548

GenCC curated gene-disease

Disease	Classification	Inheritance
Usmani-Riazuddin syndrome, autosomal dominant	Strong	Autosomal dominant
Usmani-Riazuddin syndrome, autosomal recessive	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Semidominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	AD
complex neurodevelopmental disorder	Limited	AR

Mondo (4): Usmani-Riazuddin syndrome, autosomal dominant (MONDO:0859174), Usmani-Riazuddin syndrome, autosomal recessive (MONDO:0859196), neurodevelopmental disorder (MONDO:0700092), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000262	Turricephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000336	Prominent supraorbital ridges
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000486	Strabismus
HP:0000565	Esotropia
HP:0000646	Amblyopia
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001382	Joint hypermobility
HP:0001763	Pes planus

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003262_267	Post bronchodilator FEV1	4.000000e-06
GCST003262_271	Post bronchodilator FEV1	2.000000e-06
GCST003262_272	Post bronchodilator FEV1	3.000000e-06
GCST003262_541	Post bronchodilator FEV1	1.000000e-06
GCST003262_846	Post bronchodilator FEV1	4.000000e-06
GCST006269_1035	General cognitive ability	2.000000e-08
GCST009256_13	Superior temporal sulcus banks volume	7.000000e-06
GCST010002_114	Refractive error	4.000000e-10
GCST010242_345	HDL cholesterol levels	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004337	intelligence
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067033 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.79	Kd	162.6	nM	CHEMBL3752910
6.79	ED50	162.6	nM	CHEMBL3752910
5.86	Kd	1371	nM	CHEMBL5653589
5.86	ED50	1371	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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	2147861: Binding affinity to human AP1G1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1626	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147861: Binding affinity to human AP1G1 incubated for 45 mins by Kinobead based pull down assay	kd	1.3711	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	increases expression, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
methoxyacetic acid	affects cotreatment, increases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
PCI 5002	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	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
CHEMBL5650903	Binding	Binding affinity to human AP1G1 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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AR67	HeLa-Mitotrap-Ap1g1-FKBP	Cancer cell line	Female
CVCL_SC69	HAP1 AP1G1 (-) 1	Cancer cell line	Male
CVCL_SC70	HAP1 AP1G1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age