AUP1

Summary

AUP1 (AUP1 lipid droplet regulating VLDL assembly factor, HGNC:891) is a protein-coding gene on chromosome 2p13.1, encoding Lipid droplet-regulating VLDL assembly factor AUP1 (Q9Y679). Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome.

The protein encoded this gene is involved in several pathways including quality control of misfolded proteins in the endoplasmic reticulum and lipid droplet accumulation. Lipid droplets are organelles in the cytoplasm that store neutral lipids such as cholesterol esters and trigylycerides to prevent the overabundance of free cholesterol and fatty acids in cells, but also to act as storage for other metabolic processes, such as membrane biogenesis. Reduced expression of this gene results in reduced lipid droplet clustering, a function that is dependent on ubiquitination of the protein. This protein contains multiple domains including a hydrophobic N-terminal domain, an acetyltranferase domain, a ubiquitin-binding CUE domain, and a UBE2B2-binding domain (G2BR). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 550 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 108 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_181575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:891
Approved symbol	AUP1
Name	AUP1 lipid droplet regulating VLDL assembly factor
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115307
Ensembl biotype	protein_coding
OMIM	602434
Entrez	550

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 26 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000377526, ENST00000425118, ENST00000462297, ENST00000463900, ENST00000464887, ENST00000466894, ENST00000472800, ENST00000486234, ENST00000890021, ENST00000890022, ENST00000890023, ENST00000890024, ENST00000890025, ENST00000890026, ENST00000890027, ENST00000890028, ENST00000890029, ENST00000890030, ENST00000890031, ENST00000890032, ENST00000890033, ENST00000890034, ENST00000890035, ENST00000890036, ENST00000890037, ENST00000936886, ENST00000936887, ENST00000936888, ENST00000936889, ENST00000936890, ENST00000954390, ENST00000954391, ENST00000954392

RefSeq mRNA: 1 — MANE Select: NM_181575 NM_181575

CCDS: CCDS42702

Canonical transcript exons

ENST00000377526 — 12 exons

Exon	Start	End
ENSE00000763330	74528751	74528935
ENSE00001474222	74529132	74529282
ENSE00001899347	74526652	74526836
ENSE00001925372	74529580	74529706
ENSE00003479428	74527248	74527363
ENSE00003532064	74527736	74527838
ENSE00003588076	74528248	74528321
ENSE00003588999	74528417	74528489
ENSE00003597573	74529362	74529499
ENSE00003599800	74526941	74527059
ENSE00003664341	74527471	74527590
ENSE00003676481	74527940	74528006

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.4424 / max 278.9740, expressed in 1815 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29238	50.3797	1814
29239	2.0066	1325
29240	0.9981	715
29237	0.6584	387
29233	0.2300	112
29234	0.1697	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.92	gold quality
body of pancreas	UBERON:0001150	98.86	gold quality
lower esophagus mucosa	UBERON:0035834	98.72	gold quality
mucosa of transverse colon	UBERON:0004991	98.64	gold quality
body of stomach	UBERON:0001161	98.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.62	gold quality
left lobe of thyroid gland	UBERON:0001120	98.45	gold quality
right lobe of thyroid gland	UBERON:0001119	98.43	gold quality
transverse colon	UBERON:0001157	98.42	gold quality
tendon of biceps brachii	UBERON:0008188	98.42	gold quality
spleen	UBERON:0002106	98.35	gold quality
right lobe of liver	UBERON:0001114	98.29	gold quality
metanephros cortex	UBERON:0010533	98.29	gold quality
minor salivary gland	UBERON:0001830	98.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.19	gold quality
right ovary	UBERON:0002118	98.18	gold quality
body of uterus	UBERON:0009853	98.18	gold quality
endocervix	UBERON:0000458	98.13	gold quality
adenohypophysis	UBERON:0002196	98.13	gold quality
left ovary	UBERON:0002119	98.12	gold quality
upper lobe of left lung	UBERON:0008952	98.11	gold quality
omental fat pad	UBERON:0010414	98.11	gold quality
peritoneum	UBERON:0002358	98.08	gold quality
right lung	UBERON:0002167	98.06	gold quality
cerebellar hemisphere	UBERON:0002245	98.03	gold quality
rectum	UBERON:0001052	98.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.98	gold quality
left uterine tube	UBERON:0001303	97.97	gold quality
skin of abdomen	UBERON:0001416	97.97	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting AUP1, 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-6870-5P	99.99	68.55	2115
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-570-3P	99.96	72.41	4910
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-571	95.38	66.54	671
HSA-MIR-6741-3P	89.67	61.63	69

Literature-anchored findings (GeneRIF, showing 12)

• binding of Aup1 plays a crucial role in the alpha(IIb)beta(3) inside-out signaling (PMID:12042322)
• molecular cloning and sequencing of cDNA and preliminary characterization of protein (PMID:12534237)
• The presence of the AUP1-Ube2g2 complex at LDs provides a direct molecular link between LDs and the cellular ubiquitination machinery. (PMID:21127063)
• Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and endoplasmic reticulum (ER) protein quality control. (PMID:21857022)
• AUP1 targeting signals (PMID:23197321)
• A novel role for Aup1 in maintenance of intracellular cholesterol homeostasis via mediation of the endoplasmic reticulum associated degradation of HMG-CoA reductase. (PMID:23223569)
• Monoubiquitinated AUP1 on the lipid droplet surface specifically induces clustering. (PMID:24039768)
• AUP1 may be a crucial factor in hepatic apoB100 quality control, determining the rate at which apoB100 is degraded or lipidated to enable VLDL particle assembly and secretion. (PMID:28183703)
• A structurally conserved site in AUP1 binds the E2 enzyme UBE2G2 and is essential for ER-associated degradation. (PMID:34879065)
• AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma. (PMID:35633317)
• AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2. (PMID:38474353)
• AUP1 transcriptionally activated by KDM5B reprograms lipid metabolism to promote the malignant progression of cervical cancer. (PMID:39329209)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	aup1	ENSDARG00000092609
mus_musculus	Aup1	ENSMUSG00000068328
rattus_norvegicus	Aup1	ENSRNOG00000007842
caenorhabditis_elegans		WBGENE00018408

Protein

Protein identifiers

Lipid droplet-regulating VLDL assembly factor AUP1 — Q9Y679 (reviewed: Q9Y679)

Alternative names: Ancient ubiquitous protein 1

All UniProt accessions (1): Q9Y679

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome. Plays a role in lipid droplet formation. Induces lipid droplet clustering. Recruits ubiquitin-conjugating enzyme UBE2G2 to lipid droplets which facilitates its interaction with ubiquitin ligases AMFR/gp78 and RNF139/TRC8, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation. Also required for the degradation of INSIG1, SREBF1 and SREBF2. Plays a role in regulating assembly and secretion of very low density lipoprotein particles and stability of apolipoprotein APOB. (Microbial infection) Following Dengue virus infection, required for induction of lipophagy which facilitates production of virus progeny particles.

Subunit / interactions. Identified in a complex that contains SEL1L, OS9, FAF2/UBXD8, UBE2J1/UBC6E and AUP1. Interacts with the cytoplasmic tail of ITGA2B, ITGA1, ITGA2, ITGA5, ITGAV and ITGAM. Interacts (via C-terminus) with ubiquitin-conjugating enzyme UBE2G2; the interaction recruits UBE2G2 to lipid droplets. Interacts with ubiquitin ligases AMFR/gp78 and RNF139/TRC8; this promotes interaction of UBE2G2 with AMFR and RNF139. Interacts with apolipoprotein APOB. (Microbial infection) Interacts with Dengue virus NS4A; the interaction occurs in the presence of Dengue virus NS4B and induces lipophagy which facilitates production of virus progeny.

Subcellular location. Endoplasmic reticulum membrane. Lipid droplet Cytoplasmic vesicle. Autophagosome.

Tissue specificity. Detected in blood platelets and leukocytes (at protein level). Ubiquitous. Highly expressed in placenta, liver, kidney, skeletal muscle, heart and brain.

Post-translational modifications. Monoubiquitinated and diubiquitinated. (Microbial infection) Not ubiquitinated following Dengue virus infection.

Domain organisation. The CUE domain is required for interaction with the ER quality control machinery and misfolded substrates, ubiquitination, lipid clustering and interaction with AMFR but is not required for localization to lipid droplets.

Induction. (Microbial infection) By Dengue virus infection (at protein level).

Similarity. Belongs to the AUP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y679-2	1	yes
Q9Y679-3	2

RefSeq proteins (1): NP_853553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003892	CUE	Domain
IPR048056	AUP1_CUE	Domain

Pfam: PF02845

UniProt features (48 total): mutagenesis site 27, modified residue 6, helix 4, topological domain 2, splice variant 2, region of interest 2, chain 1, intramembrane region 1, domain 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7LEW	X-RAY DIFFRACTION	1.74
2EKF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y679-F1	80.19	0.27

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 (6): 292, 363, 367, 1, 5, 288

Mutagenesis-validated functional residues (27):

Position	Phenotype
33–35	disrupts topology with the n-terminus in the lumen instead of the cytoplasm. abolishes lipid droplet localization and li
42	abolishes lipid droplet localization.
58	does not affect lipid droplet localization.
62–63	abolishes lipid droplet localization.
96	reduced formation of lipid droplets.
306–308	reduced interaction with er quality control machinery and misfolded substrates; when associated with 333-l-l-334 del.
307–309	reduced lipid droplet clustering.
316	reduced lipid droplet clustering; when associated with 319-v-e-320 and 333-e-d-334.
319–320	reduced lipid droplet clustering; when associated with r-316 and 333-e-d-334.
329–330	reduced lipid droplet clustering.
333–334	reduced lipid droplet clustering; when associated with r-316 and 319-v-e-320.
333–334	reduced interaction with er quality control machinery and misfolded substrates; when associated with 306-k–a-308.
382	significantly reduced interaction with ube2g2.
383	significantly reduced interaction with ube2g2.
384	no effect on interaction with ube2g2.
386	abolishes interaction with ube2g2.
388	no effect on interaction with ube2g2.
389	significantly reduced interaction with ube2g2.
390	abolishes interaction with ube2g2.
393	abolishes interaction with ube2g2.
397–402	abolishes interaction with ube2g2.
398	significantly reduced interaction with ube2g2.
399	no effect on interaction with ube2g2.
400	abolishes interaction with ube2g2.
404	abolishes interaction with ube2g2.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 122 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_503, GOBP_MACROAUTOPHAGY, ONKEN_UVEAL_MELANOMA_UP, MODULE_195, AAAGGGA_MIR204_MIR211, GOBP_ORGANELLE_ASSEMBLY, MODULE_147, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, CCCAGAG_MIR326

GO Biological Process (7): response to virus (GO:0009615), retrograde protein transport, ER to cytosol (GO:0030970), lipid droplet organization (GO:0034389), ERAD pathway (GO:0036503), lipophagy (GO:0061724), lipid droplet formation (GO:0140042), protein localization to lipid droplet (GO:1990044)

GO Molecular Function (4): ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin protein ligase binding (GO:0031625), ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (7): autophagosome (GO:0005776), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
response to other organism	1
protein exit from endoplasmic reticulum	1
ERAD pathway	1
endoplasmic reticulum to cytosol transport	1
organelle organization	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
macroautophagy	1
lipid droplet disassembly	1
lipid storage	1
lipid droplet organization	1
membraneless organelle assembly	1
protein localization to organelle	1
ubiquitin-like protein conjugating enzyme binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-like protein binding	1
binding	1
vacuole	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
cellular anatomical structure	1
intracellular vesicle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AUP1	UBE2G2	P56554	994
AUP1	FAF2	Q96CS3	992
AUP1	DERL2	Q9GZP9	983
AUP1	SEL1L	Q9UBV2	949
AUP1	OS9	Q13438	935
AUP1	UBE2J1	Q9Y385	902
AUP1	SYVN1	Q86TM6	882
AUP1	VCP	P55072	851
AUP1	CANX	P27824	827
AUP1	GGH	Q92820	803
AUP1	HSPA5	P11021	794
AUP1	P4HB	P07237	780
AUP1	SELENOS	Q9BQE4	776
AUP1	DERL3	Q96Q80	720
AUP1	ERLEC1	Q96DZ1	716

IntAct

153 interactions, top by confidence:

A	B	Type	Score
SEL1L	OS9	psi-mi:“MI:0914”(association)	0.860
UBE2G2	AUP1	psi-mi:“MI:0915”(physical association)	0.750
AUP1	UBE2G2	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SYVN1	OS9	psi-mi:“MI:0914”(association)	0.690
VCP	UBXN8	psi-mi:“MI:0914”(association)	0.690
AUP1	APOB	psi-mi:“MI:0403”(colocalization)	0.610
AUP1	APOB	psi-mi:“MI:2364”(proximity)	0.610
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
AUP1	APOB	psi-mi:“MI:0914”(association)	0.610
AUP1	SYVN1	psi-mi:“MI:0914”(association)	0.600
OPRM1	AUP1	psi-mi:“MI:0915”(physical association)	0.580
AUP1	GPR35	psi-mi:“MI:0915”(physical association)	0.550
APOB	VCP	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530

BioGRID (377): AUP1 (Two-hybrid), AUP1 (Reconstituted Complex), AUP1 (Affinity Capture-Western), AUP1 (Affinity Capture-Western), AUP1 (Affinity Capture-Western), CAPRIN2 (Affinity Capture-MS), UBE2G2 (Affinity Capture-MS), DIP2B (Affinity Capture-MS), SEL1L (Affinity Capture-MS), AUP1 (Affinity Capture-MS), SURF4 (Affinity Capture-MS), PRKDC (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), UBE2G2 (Affinity Capture-Western), SYVN1 (Affinity Capture-Western)

ESM2 similar proteins: A1L134, A9ULG4, B1H1N7, B2RUP2, D3ZI76, D3ZUM2, F1MLB4, I3L5V6, O95870, P47823, P70295, Q13144, Q14DK4, Q16586, Q1HAQ0, Q1JPD2, Q1LWG4, Q27J81, Q2TBP5, Q3TFD2, Q4R8P0, Q5NVK5, Q5R6S0, Q64350, Q643R3, Q6MG55, Q6NUI2, Q6NVG1, Q6PBN5, Q6PDS3, Q6SZW1, Q6V7V2, Q70J99, Q7TN37, Q8CHW4, Q8N0W3, Q8N9W5, Q8NF37, Q8TE02, Q95K25

Diamond homologs: A1L134, A9ULG4, B1H1N7, P34426, P70295, Q6PBN5, Q9Y679, F1QB30

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 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
Amino acid transport across the plasma membrane	5	14.2×	1e-03
Hh mutants are degraded by ERAD	6	13.8×	6e-04
Defective CFTR causes cystic fibrosis	6	12.4×	7e-04
Hedgehog ligand biogenesis	6	12.0×	8e-04
Regulation of RAS by GAPs	5	9.1×	4e-03
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	9.1×	4e-03
Signaling by BRAF and RAF1 fusions	5	8.0×	5e-03
ABC-family protein mediated transport	6	6.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde protein transport, ER to cytosol	5	37.0×	9e-05
amino acid transport	8	18.6×	1e-05
ERAD pathway	7	9.5×	3e-03
G protein-coupled receptor signaling pathway	15	4.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	68
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2425831	NC_000002.11:g.(?74753829)(74757416_?)del	Pathogenic
155389	GRCh38/hg38 2p13.1-12(chr2:74375779-75517520)x1	Likely pathogenic

SpliceAI

1522 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74526834:CTC:C	acceptor_gain	1.0000
2:74527243:CTCA:C	donor_loss	1.0000
2:74527244:TCA:T	donor_loss	1.0000
2:74527245:CA:C	donor_loss	1.0000
2:74527247:CC:C	donor_loss	1.0000
2:74527359:CTTGG:C	acceptor_gain	1.0000
2:74527360:TTGGC:T	acceptor_loss	1.0000
2:74527363:GCTGG:G	acceptor_loss	1.0000
2:74527364:C:CC	acceptor_gain	1.0000
2:74527364:C:T	acceptor_loss	1.0000
2:74527515:T:TA	donor_gain	1.0000
2:74527516:C:A	donor_gain	1.0000
2:74527731:CATA:C	donor_loss	1.0000
2:74527733:TA:T	donor_loss	1.0000
2:74527734:A:AC	donor_gain	1.0000
2:74527735:C:CC	donor_gain	1.0000
2:74527735:C:CG	donor_loss	1.0000
2:74527735:CCTGA:C	donor_gain	1.0000
2:74527835:CCAG:C	acceptor_gain	1.0000
2:74527836:CAG:C	acceptor_gain	1.0000
2:74527836:CAGC:C	acceptor_gain	1.0000
2:74527839:C:CC	acceptor_gain	1.0000
2:74528490:C:CC	acceptor_gain	1.0000
2:74529341:C:A	donor_gain	1.0000
2:74529574:TCTTA:T	donor_loss	1.0000
2:74529575:CTTAC:C	donor_loss	1.0000
2:74529576:TTACC:T	donor_loss	1.0000
2:74529577:TACC:T	donor_loss	1.0000
2:74529579:C:CG	donor_loss	1.0000
2:74526835:TC:T	acceptor_gain	0.9900

AlphaMissense

2616 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74528796:G:T	P160H	0.997
2:74526967:C:A	K390N	0.996
2:74526967:C:G	K390N	0.996
2:74528258:A:C	Y221D	0.996
2:74529169:T:A	D101V	0.995
2:74529250:C:T	G74E	0.995
2:74528753:G:C	F174L	0.994
2:74528753:G:T	F174L	0.994
2:74528755:A:G	F174L	0.994
2:74526971:C:G	R389P	0.993
2:74527327:A:G	L333P	0.993
2:74527521:A:T	V304D	0.993
2:74528285:A:G	W212R	0.993
2:74528285:A:T	W212R	0.993
2:74528754:A:G	F174S	0.993
2:74526972:G:T	R389S	0.992
2:74527336:A:T	I330N	0.992
2:74529169:T:G	D101A	0.992
2:74529170:C:A	D101Y	0.992
2:74529170:C:G	D101H	0.992
2:74529446:C:T	G35E	0.992
2:74529447:C:G	G35R	0.992
2:74529447:C:T	G35R	0.992
2:74527473:A:G	L320P	0.991
2:74527785:T:A	K264N	0.991
2:74527785:T:G	K264N	0.991
2:74528796:G:C	P160R	0.991
2:74529186:G:C	N95K	0.991
2:74529186:G:T	N95K	0.991
2:74529251:C:G	G74R	0.991

dbSNP variants (sampled 300 via entrez): RS1002947900 (2:74526442 A>G,T), RS1005256682 (2:74526384 G>A), RS1005850181 (2:74527933 C>T), RS1006310756 (2:74526682 T>A,C), RS1007852428 (2:74530519 G>A), RS1010979891 (2:74530448 A>C,G), RS1012007138 (2:74531541 GC>G), RS1012038303 (2:74531186 G>A), RS1012713980 (2:74528242 T>A), RS1013074327 (2:74528596 G>A), RS1013662403 (2:74529786 C>A,T), RS1015017139 (2:74526410 G>T), RS1015986606 (2:74527723 A>G), RS1016742866 (2:74528409 ACACT>A), RS1017400756 (2:74529225 G>A,C,T)

Disease associations

OMIM: gene MIM:602434 | disease phenotypes: MIM:610297

GenCC curated gene-disease

Mondo (1): Parkinson disease 13, autosomal dominant, susceptibility to (MONDO:0012466)

Orphanet (1): Young-onset Parkinson disease (Orphanet:2828)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565204	Parkinson Disease 13 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067077 (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
5.21	Kd	6217	nM	CHEMBL5653589
5.20	ED50	6282	nM	CHEMBL5653589

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147931: Binding affinity to human AUP1 incubated for 45 mins by Kinobead based pull down assay	kd	6.2175	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Cadmium	increases abundance, increases palmitoylation, decreases reaction	1
Caffeine	decreases phosphorylation	1
Diazinon	increases methylation	1
Estradiol	affects expression	1
Lead	decreases expression	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	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
CHEMBL5650973	Binding	Binding affinity to human AUP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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