AP1S1

Summary

AP1S1 (adaptor related protein complex 1 subunit sigma 1, HGNC:559) is a protein-coding gene on chromosome 7q22.1, encoding AP-1 complex subunit sigma-1A (P61966). 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 protein encoded by this gene is part of the clathrin coat assembly complex which links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. This protein, as well as beta-prime-adaptin, gamma-adaptin, and the medium (mu) chain AP47, form the AP-1 assembly protein complex located at the Golgi vesicle.

Source: NCBI Gene 1174 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MEDNIK syndrome (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 159 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes
• MANE Select transcript: NM_001283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:559
Approved symbol	AP1S1
Name	adaptor related protein complex 1 subunit sigma 1
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	AP19, SIGMA1A, WUGSC:H_DJ0747G18.2
Ensembl gene	ENSG00000106367
Ensembl biotype	protein_coding
OMIM	603531
Entrez	1174

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000337619, ENST00000429457, ENST00000443943, ENST00000643104, ENST00000646560, ENST00000646950, ENST00000856012, ENST00000856013, ENST00000926140, ENST00000926141, ENST00000926142, ENST00000926143, ENST00000926144

RefSeq mRNA: 1 — MANE Select: NM_001283 NM_001283

CCDS: CCDS47669

Canonical transcript exons

ENST00000337619 — 5 exons

Exon	Start	End
ENSE00000712174	101157377	101157485
ENSE00001108742	101159059	101159196
ENSE00001363395	101160519	101161276
ENSE00001422522	101156594	101156772
ENSE00001434906	101154476	101154517

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5522 / max 421.0361, expressed in 1790 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80169	34.8257	1786
80167	1.4706	941
80168	0.9006	605
80170	0.3554	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.59	gold quality
stromal cell of endometrium	CL:0002255	97.13	gold quality
mucosa of transverse colon	UBERON:0004991	97.13	gold quality
prefrontal cortex	UBERON:0000451	96.94	gold quality
nucleus accumbens	UBERON:0001882	96.93	gold quality
right frontal lobe	UBERON:0002810	96.80	gold quality
islet of Langerhans	UBERON:0000006	96.60	gold quality
caudate nucleus	UBERON:0001873	96.20	gold quality
putamen	UBERON:0001874	96.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.95	gold quality
amygdala	UBERON:0001876	95.64	gold quality
ganglionic eminence	UBERON:0004023	95.59	gold quality
cingulate cortex	UBERON:0003027	95.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.24	gold quality
anterior cingulate cortex	UBERON:0009835	95.20	gold quality
rectum	UBERON:0001052	94.86	gold quality
frontal cortex	UBERON:0001870	94.39	gold quality
neocortex	UBERON:0001950	94.35	gold quality
skin of leg	UBERON:0001511	93.92	gold quality
telencephalon	UBERON:0001893	93.83	gold quality
adrenal tissue	UBERON:0018303	93.64	gold quality
ventricular zone	UBERON:0003053	93.54	gold quality
cerebral cortex	UBERON:0000956	93.40	gold quality
forebrain	UBERON:0001890	93.36	gold quality
skin of abdomen	UBERON:0001416	93.14	gold quality
type B pancreatic cell	CL:0000169	92.96	gold quality
gall bladder	UBERON:0002110	92.84	gold quality
transverse colon	UBERON:0001157	92.67	gold quality
olfactory bulb	UBERON:0002264	92.65	gold quality
metanephros cortex	UBERON:0010533	92.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting AP1S1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-7110-5P	99.80	67.84	1712

Literature-anchored findings (GeneRIF, showing 4)

• A splice mutation in AP1S1 was found in four families with a neurocutaneous syndrome. (PMID:19057675)
• Isolation and description of the rat and mouse genes. (PMID:2040623)
• We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular copper machinery mediated by copper-pump proteins (PMID:23423674)
• AP1S1 missense mutations cause a congenital enteropathy via an epithelial barrier defect. (PMID:32306098)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	AP1S1	ENSDARG00000098990
mus_musculus	Ap1s1	ENSMUSG00000004849
rattus_norvegicus	Ap1s1	ENSRNOG00000001415
drosophila_melanogaster	AP-1sigma	FBGN0039132
caenorhabditis_elegans		WBGENE00000159

Paralogs (6): AP2S1 (ENSG00000042753), AP4S1 (ENSG00000100478), AP1S3 (ENSG00000152056), AP3S2 (ENSG00000157823), AP3S1 (ENSG00000177879), AP1S2 (ENSG00000182287)

Protein

Protein identifiers

AP-1 complex subunit sigma-1A — P61966 (reviewed: P61966)

Alternative names: Adaptor protein complex AP-1 subunit sigma-1A, Adaptor-related protein complex 1 subunit sigma-1A, Clathrin assembly protein complex 1 sigma-1A small chain, Clathrin coat assembly protein AP19, Golgi adaptor HA1/AP1 adaptin sigma-1A subunit, HA1 19 kDa subunit, Sigma 1a subunit of AP-1 clathrin, Sigma-adaptin 1A, Sigma1A-adaptin

All UniProt accessions (4): P61966, A0A2R8Y7S3, A0A2R8YGH5, H7C1E4

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.

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).

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

Tissue specificity. Widely expressed.

Disease relevance. MEDNIK syndrome (MEDNIK) [MIM:609313] A disorder characterized by erythematous skin lesions and hyperkeratosis, severe psychomotor retardation, peripheral neuropathy, sensorineural hearing loss, together with elevated very-long-chain fatty acids and severe congenital diarrhea. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in response to enterovirus 71 (EV71) infection.

Similarity. Belongs to the adaptor complexes small subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
P61966-1	1	yes
P61966-2	2

RefSeq proteins (1): NP_001274* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000804	Clathrin_sm-chain_CS	Conserved_site
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR016635	AP_complex_ssu	Family
IPR022775	AP_mu_sigma_su	Domain
IPR044733	AP1_sigma	Family

Pfam: PF01217

UniProt features (14 total): strand 6, helix 5, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4P6Z	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61966-F1	94.83	0.90

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 (1): 147

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: 265 (showing top): RNGTGGGC_UNKNOWN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, E2F4DP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, DITTMER_PTHLH_TARGETS_UP, GOBP_CELLULAR_PIGMENTATION, KEGG_LYSOSOME, GTTAAAG_MIR302B, REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (9): intracellular protein transport (GO:0006886), receptor-mediated endocytosis (GO:0006898), response to virus (GO:0009615), vesicle-mediated transport (GO:0016192), retrograde transport, endosome to Golgi (GO:0042147), platelet dense granule organization (GO:0060155), basolateral protein secretion (GO:0110010), melanosome assembly (GO:1903232), protein transport (GO:0015031)

GO Molecular Function (1): clathrin-cargo adaptor activity (GO:0035615)

GO Cellular Component (14): Golgi membrane (GO:0000139), 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), cytoplasmic vesicle membrane (GO:0030659), trans-Golgi network membrane (GO:0032588), terminal bouton (GO:0043195), membrane coat (GO:0030117), cytoplasmic vesicle (GO:0031410), presynapse (GO:0098793)

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
cytoplasm	4
cellular anatomical structure	3
intracellular protein localization	2
transport	2
endomembrane system	2
protein transport	1
intracellular transport	1
endocytosis	1
response to other organism	1
cellular process	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
secretory granule organization	1
protein secretion	1
melanosome organization	1
organelle assembly	1
establishment of protein localization	1
clathrin binding	1
cargo adaptor activity	1
Golgi apparatus	1
bounding membrane of organelle	1
lysosome	1
lytic vacuole membrane	1
endosome	1
intracellular membrane-bounded organelle	1
membrane	1
clathrin coat of trans-Golgi network vesicle	1
clathrin adaptor complex	1
vesicle membrane	1
cytoplasmic vesicle	1
trans-Golgi network	1
organelle membrane	1
axon terminus	1
presynapse	1
coated membrane	1
membrane protein complex	1
intracellular vesicle	1
synapse	1

Protein interactions and networks

STRING

1022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP1S1	AP1M1	Q9BXS5	994
AP1S1	AP1G2	O75843	890
AP1S1	AP1B1	P78436	888
AP1S1	AP1M2	Q9Y6Q5	845
AP1S1	AP1G1	O43747	795
AP1S1	GJC3	Q8NFK1	788
AP1S1	EBLN2	Q6P2I7	719
AP1S1	GGA1	Q9UJY5	696
AP1S1	AGAP1	Q9UPQ3	667
AP1S1	GJB3	O75712	646
AP1S1	GGA3	Q9NZ52	616
AP1S1	GSTM1	P09488	603
AP1S1	CSNK2A1	P19138	555
AP1S1	ARF1	P10947	512
AP1S1	RABGEF1	Q9UJ41	507

IntAct

48 interactions, top by confidence:

A	B	Type	Score
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
AP1B1	vpu	psi-mi:“MI:0915”(physical association)	0.400
Ap1g1		psi-mi:“MI:0915”(physical association)	0.400
AP1B1		psi-mi:“MI:0915”(physical association)	0.400
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
AP2M1	C1orf226	psi-mi:“MI:0914”(association)	0.350
AP1M2	AP1G1	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MRFAP1L1	MYO9A	psi-mi:“MI:0914”(association)	0.350
AP2B1	SYNJ1	psi-mi:“MI:0914”(association)	0.350
AP1B1	SYNJ1	psi-mi:“MI:0914”(association)	0.350
COMT	AP1G1	psi-mi:“MI:0914”(association)	0.350
SPATA33	AP1G1	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
AP2B1	AP1G1	psi-mi:“MI:0914”(association)	0.350
AP2M1	PER1	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
DNAJB2		psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
HEATR3	PLD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): AP1S1 (Affinity Capture-RNA), AP1S1 (Affinity Capture-MS), AP1S1 (Affinity Capture-MS), AP1G1 (Co-fractionation), AP1S1 (Co-fractionation), AP1S1 (Co-fractionation), AP1S1 (Co-fractionation), AP1S1 (Co-fractionation), AP1S1 (Co-fractionation), AP1S1 (Affinity Capture-MS), AP1S1 (Affinity Capture-MS), AP1S1 (Reconstituted Complex), AP1S1 (Affinity Capture-MS), AP1S1 (Affinity Capture-MS), AP1S1 (Affinity Capture-RNA)

ESM2 similar proteins: B0G185, O02173, O17901, O23685, O43041, O50016, O82201, P35181, P35604, P47064, P53290, P53680, P56377, P61923, P61924, P61966, P61967, P62743, P62744, Q00381, Q09905, Q17QC5, Q1JQ98, Q28IG8, Q3ZBB6, Q3ZBS3, Q4ICG5, Q4WS49, Q54H39, Q54NZ4, Q54WW3, Q553S2, Q557G3, Q59QC5, Q5BFF8, Q5R5F2, Q5R940, Q5ZKP4, Q75F71, Q7SAQ1

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AP1S1	“form complex”	“AP-1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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	100.2×	2e-09
The role of Nef in HIV-1 replication and disease pathogenesis	6	100.2×	2e-09
Host Interactions of HIV factors	6	53.0×	6e-08
Lysosome Vesicle Biogenesis	6	51.5×	6e-08
Golgi Associated Vesicle Biogenesis	6	31.6×	8e-07
MHC class II antigen presentation	8	18.8×	3e-07
HIV Infection	6	18.8×	1e-05
Clathrin-mediated endocytosis	7	15.7×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle endocytosis	7	63.0×	6e-09
clathrin-dependent endocytosis	5	60.5×	3e-06
vesicle-mediated transport	8	16.1×	4e-06
intracellular protein transport	9	12.2×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	21
Likely benign	100
Benign	22

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2969619	NM_001283.5(AP1S1):c.60C>G (p.Tyr20Ter)	Pathogenic
3245870	NC_000007.13:g.(?100797796)(100797818_?)del	Pathogenic
39854	NM_001283.5(AP1S1):c.183-2A>G	Pathogenic
503720	NM_001283.5(AP1S1):c.364dup (p.Asp122fs)	Likely pathogenic
804404	NM_001283.5(AP1S1):c.364del (p.Asp122fs)	Likely pathogenic

SpliceAI

696 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101154513:GGATG:G	donor_gain	1.0000
7:101154514:GATGG:G	donor_gain	1.0000
7:101154515:A:T	donor_gain	1.0000
7:101156770:G:GT	donor_gain	1.0000
7:101156770:GAG:G	donor_gain	1.0000
7:101157372:CGCA:C	acceptor_loss	1.0000
7:101157373:GCA:G	acceptor_loss	1.0000
7:101157374:CA:C	acceptor_loss	1.0000
7:101157375:A:AG	acceptor_gain	1.0000
7:101157376:G:GG	acceptor_gain	1.0000
7:101157376:G:GT	acceptor_loss	1.0000
7:101157376:GAT:G	acceptor_gain	1.0000
7:101157376:GATAT:G	acceptor_gain	1.0000
7:101157481:GCAGT:G	donor_gain	1.0000
7:101157482:CAGT:C	donor_gain	1.0000
7:101157483:AGT:A	donor_gain	1.0000
7:101157483:AGTG:A	donor_loss	1.0000
7:101157484:GT:G	donor_gain	1.0000
7:101157484:GTG:G	donor_gain	1.0000
7:101157485:TGT:T	donor_gain	1.0000
7:101157485:TGTA:T	donor_loss	1.0000
7:101157486:G:GG	donor_gain	1.0000
7:101157487:T:A	donor_loss	1.0000
7:101159054:CCCAG:C	acceptor_loss	1.0000
7:101159056:CAGG:C	acceptor_loss	1.0000
7:101159057:A:AG	acceptor_gain	1.0000
7:101159057:AGGT:A	acceptor_gain	1.0000
7:101159058:G:GG	acceptor_gain	1.0000
7:101159058:GGT:G	acceptor_gain	1.0000
7:101159058:GGTG:G	acceptor_gain	1.0000

AlphaMissense

1042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101157382:C:A	A63D	1.000
7:101157384:A:C	S64R	1.000
7:101157386:C:A	S64R	1.000
7:101157386:C:G	S64R	1.000
7:101157388:T:A	L65H	1.000
7:101157388:T:C	L65P	1.000
7:101157463:T:C	L90P	1.000
7:101157477:T:C	F95L	1.000
7:101157479:T:A	F95L	1.000
7:101157479:T:G	F95L	1.000
7:101159063:G:A	C99Y	1.000
7:101159065:G:A	E100K	1.000
7:101159066:A:T	E100V	1.000
7:101159067:G:C	E100D	1.000
7:101159067:G:T	E100D	1.000
7:101159069:T:A	L101Q	1.000
7:101159069:T:C	L101P	1.000
7:101159072:A:C	D102A	1.000
7:101159072:A:T	D102V	1.000
7:101159078:T:A	I104N	1.000
7:101159080:T:C	F105L	1.000
7:101159082:C:A	F105L	1.000
7:101159082:C:G	F105L	1.000
7:101156615:A:C	S9R	0.999
7:101156617:C:A	S9R	0.999
7:101156617:C:G	S9R	0.999
7:101156625:G:A	G12E	0.999
7:101156637:T:C	L16P	0.999
7:101156763:T:A	V58D	0.999
7:101156770:G:C	K60N	0.999

dbSNP variants (sampled 300 via entrez): RS1000169903 (7:101160375 C>A,G,T), RS1000347099 (7:101156290 A>G), RS1000376645 (7:101161587 C>A,T), RS1000575810 (7:101156287 T>A,C), RS1001940078 (7:101158763 C>T), RS1002333718 (7:101159605 CTCTTTTTTTTT>C), RS1002458278 (7:101153038 T>C), RS1002564916 (7:101153847 C>A,T), RS1002681171 (7:101160284 G>A,T), RS1002784338 (7:101154534 G>C,T), RS1002942438 (7:101154182 C>G), RS1003340354 (7:101158317 G>A), RS1003412325 (7:101158008 C>T), RS1003961466 (7:101161191 A>G,T), RS1004017870 (7:101160122 C>T)

Disease associations

OMIM: gene MIM:603531 | disease phenotypes: MIM:609313, MIM:613329

GenCC curated gene-disease

Disease	Classification	Inheritance
MEDNIK syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
MEDNIK syndrome	Definitive	AR

Mondo (2): MEDNIK syndrome (MONDO:0012251), congenital plasminogen activator inhibitor type 1 deficiency (MONDO:0013227)

Orphanet (2): MEDNIK syndrome (Orphanet:171851), Congenital plasminogen activator inhibitor type 1 deficiency (Orphanet:465)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000348	High forehead
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000582	Upslanted palpebral fissure
HP:0000962	Hyperkeratosis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001406	Intrahepatic cholestasis
HP:0001510	Growth delay
HP:0001522	Death in infancy
HP:0002014	Diarrhea
HP:0002242	Abnormal intestine morphology
HP:0002580	Volvulus
HP:0003577	Congenital onset
HP:0003811	Neonatal death
HP:0003819	Death in childhood
HP:0004388	Microcolon
HP:0005235	Jejunal atresia
HP:0008064	Ichthyosis
HP:0009830	Peripheral neuropathy
HP:0010783	Erythema
HP:0010837	Decreased circulating ceruloplasmin concentration
HP:0011967	Decreased circulating copper concentration
HP:0033643	Increased circulating very long-chain fatty acid concentration

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010988_164	Adult body size	3.000000e-09
GCST012353_34	Serum metabolite concentrations in chronic kidney disease	6.000000e-15

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563739	Erythrokeratodermia Variabilis 3 (supp.)
C567640	Plasminogen Activator Inhibitor-1 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067198 (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
6.79	Kd	163	nM	CHEMBL3752910
6.79	ED50	163	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	2149827: Binding affinity to human AP1S1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1630	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Amiodarone	decreases expression, increases expression	3
sodium arsenite	increases expression	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Amitriptyline	decreases expression	2
Clomipramine	decreases expression	2
Ozone	decreases expression, affects cotreatment, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tamoxifen	decreases expression	2
Thioridazine	decreases expression	2
Valproic Acid	increases expression, affects expression	2
Cyclosporine	decreases expression	2
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
propionaldehyde	increases expression	1
bisphenol A	affects expression	1
decabromobiphenyl ether	increases expression	1
kojic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
PP242	increases 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
CHEMBL5652869	Binding	Binding affinity to human AP1S1 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

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0TN	Ubigene Hep G2 AP1S1 KO	Cancer cell line	Male
CVCL_F1RD	HyCyte LN-229 KO-hAP1S1	Cancer cell line	Female
CVCL_SC72	HAP1 AP1S1 (-) 1	Cancer cell line	Male
CVCL_SC73	HAP1 AP1S1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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