ARRDC3

Summary

ARRDC3 (arrestin domain containing 3, HGNC:29263) is a protein-coding gene on chromosome 5q14.3, encoding Arrestin domain-containing protein 3 (Q96B67). Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors.

This gene encodes a member of the arrestin family of proteins, which regulate G protein-mediated signaling. The encoded protein is thought to act as a regulator of breast cancer growth and progression by binding to a phosphorylated form of integrin beta4, a tumor-related antigen, targeting the integrin for internalization and degradation.

Source: NCBI Gene 57561 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_020801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29263
Approved symbol	ARRDC3
Name	arrestin domain containing 3
Location	5q14.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1376, TLIMP
Ensembl gene	ENSG00000113369
Ensembl biotype	protein_coding
OMIM	612464
Entrez	57561

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 3 retained_intron, 1 protein_coding

ENST00000265138, ENST00000503192, ENST00000505631, ENST00000507075, ENST00000508948, ENST00000511391, ENST00000514284

RefSeq mRNA: 4 — MANE Select: NM_020801 NM_001329670, NM_001329671, NM_001329672, NM_020801

CCDS: CCDS34202

Canonical transcript exons

ENST00000265138 — 8 exons

Exon	Start	End
ENSE00000870712	91368631	91371456
ENSE00000870713	91373684	91373838
ENSE00001151970	91374114	91374276
ENSE00001151976	91374922	91375178
ENSE00002029793	91382813	91383317
ENSE00003469625	91375511	91375613
ENSE00003612943	91376621	91376768
ENSE00003680109	91378694	91378775

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.7760 / max 1209.7141, expressed in 1820 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62555	83.8813	1817
62547	8.0855	1485
62556	1.6591	870
62550	1.4801	501
62551	0.6672	293
62553	0.4838	247
62557	0.2166	102
62552	0.1656	65
62548	0.1368	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.26	gold quality
calcaneal tendon	UBERON:0003701	99.11	gold quality
ventricular zone	UBERON:0003053	98.88	gold quality
ganglionic eminence	UBERON:0004023	98.84	gold quality
palpebral conjunctiva	UBERON:0001812	98.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.63	gold quality
amniotic fluid	UBERON:0000173	97.27	gold quality
right lobe of thyroid gland	UBERON:0001119	97.03	gold quality
gall bladder	UBERON:0002110	97.02	gold quality
cortical plate	UBERON:0005343	96.93	gold quality
left lobe of thyroid gland	UBERON:0001120	96.85	gold quality
thyroid gland	UBERON:0002046	96.82	gold quality
left adrenal gland	UBERON:0001234	96.36	gold quality
minor salivary gland	UBERON:0001830	96.32	gold quality
left adrenal gland cortex	UBERON:0035825	96.26	gold quality
adrenal gland	UBERON:0002369	96.19	gold quality
left ovary	UBERON:0002119	96.14	gold quality
islet of Langerhans	UBERON:0000006	96.09	gold quality
right ovary	UBERON:0002118	96.07	gold quality
adrenal cortex	UBERON:0001235	96.01	gold quality
right adrenal gland cortex	UBERON:0035827	95.88	gold quality
eye	UBERON:0000970	95.82	gold quality
upper leg skin	UBERON:0004262	95.80	gold quality
mouth mucosa	UBERON:0003729	95.68	gold quality
esophagus squamous epithelium	UBERON:0006920	95.63	gold quality
right adrenal gland	UBERON:0001233	95.39	gold quality
ovary	UBERON:0000992	95.35	gold quality
skin of hip	UBERON:0001554	95.33	gold quality
penis	UBERON:0000989	95.22	gold quality
vena cava	UBERON:0004087	95.10	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	10052.16
E-GEOD-93593	yes	2517.68
E-MTAB-6108	yes	825.26
E-MTAB-8142	yes	89.97
E-MTAB-6701	yes	32.92
E-MTAB-6678	yes	13.22
E-MTAB-6379	no	4274.90
E-GEOD-110499	no	1491.61
E-GEOD-106540	no	1287.37
E-CURD-89	no	1244.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

269 targeting ARRDC3, 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-188-3P	100.00	68.76	1240
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4673	100.00	66.64	1490
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-6748-5P	100.00	65.81	1057
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4645-5P	99.98	65.81	1284

Literature-anchored findings (GeneRIF, showing 25)

• [Thioredoxin-binding protein-2-like inducible membrane protein, TLIMP] TLIMP, a novel VD3- or PPARgamma ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARgamma activation. (PMID:16269462)
• Txnip regulates cellular metabolism independent of its binding to thioredoxin and the arrestin domains are crucial structural elements in metabolic functions of alpha-arrestin proteins (PMID:19605364)
• Data show that ARRDC3 interacts with NEDD4 through two conserved PPXY motifs and recruits NEDD4 to the activated beta2-adrenergic receptor. (PMID:20559325)
• ARRDC3 directly binds to a phosphorylated form of ITGbeta4 leading to its internalization, ubiquitination and ultimate degradation, and suppress breast cancer progression. (PMID:20603614)
• single-nucleotide polymorphisms in ARRDC3, FLT1, and SKAP1 were significant predictors for survival androgen-deprivation therapy in prostate cancer patients. (PMID:21652578)
• The obesity risk locus contains a single gene, arrestin domain-containing 3 (ARRDC3), which interacts directly with beta-adrenergic receptors and is gender-specific. (PMID:21982743)
• Beta 2 adrenergic receptor endocytosis requires beta-arrestin2 but not ARRDC3. (PMID:23208550)
• High affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations. (PMID:24379409)
• Promoter hypermethylation is an important mechanism of the transcriptional inactivation of ARRDC3 in invasive ductal breast carcinoma. (PMID:25148870)
• The ARRDC3 is one of six known human alpha-arrestins, and has been implicated in the downregulation of the beta2-adrenergic receptor (beta2AR). (PMID:25220262)
• We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1 (PMID:26490116)
• For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. (PMID:27109471)
• ARRDC3 functions as a switch to modulate the endosomal residence time and subsequent intracellular signaling of the beta2AR (PMID:27226565)
• correlation analysis indicated that the expression of ARRDC3 was negatively correlated with ITGbeta4 in clinical prostate cancer (PCa) tissues and cell lines. Our data revealed that ARRDC3 can serve as a tumor suppressor to inhibit PCa progression and an independent marker to predict the risk of biochemical recurrence and metastasis after radical resection of PCa. (PMID:28782483)
• a critical link between the tumor suppressor ARRDC3 and regulation of GPCR trafficking and signaling in breast cancer (PMID:29348172)
• ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP (PMID:29364502)
• ARRDC3 is involved in the infectious entry of human papillomavirus into the cell (PMID:30412241)
• Authors identified miR-200b as a major target gene of ARRDC3. miR-200b played an essential role in mediating ARRDC3 dependent reversal of EMT phenotypes and chemo-resistance to DNA damaging agents in TNBC cells. Expression of miR-200b also increased the expression of ARRDC3 as well in TNBC cells, suggesting a positive feedback loop between these two molecules. (PMID:31295851)
• Study observed that the depletion of ARRDC3 in human hepatocytes resulted in the downregulation of inflammasome pathway-associated genes and the enhancement of apoptosis of hepatic stellate cells treated with their conditioned media. Results demonstrated ARRDC3 may play a role in the development of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. (PMID:31341404)
• Upregulated ARRDC3 limits trophoblast cell invasion and tube formation and is associated with preeclampsia. (PMID:31665660)
• Arrestin domain containing 3 promotes Helicobacter pylori-associated gastritis by regulating protease-activated receptor 1. (PMID:32634127)
• alpha-Arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis. (PMID:33722977)
• ARRDC3 polymorphisms may affect the risk of glioma in Chinese Han. (PMID:34748117)
• Hsa_circ_0001740 mediates trophoblast cell function via regulating miR-188-3p/ARRDC3. (PMID:37436094)
• ARRDC3 regulates the targeted therapy sensitivity of clear cell renal cell carcinoma by promoting AXL degradation. (PMID:38389126)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	arrdc3b	ENSDARG00000036028
danio_rerio	arrdc3a	ENSDARG00000052690
mus_musculus	Arrdc3	ENSMUSG00000074794
rattus_norvegicus	Arrdc3	ENSRNOG00000045649
caenorhabditis_elegans		WBGENE00008843
caenorhabditis_elegans		WBGENE00009852
caenorhabditis_elegans		WBGENE00011052
caenorhabditis_elegans		WBGENE00011053
caenorhabditis_elegans		WBGENE00011054
caenorhabditis_elegans		WBGENE00012464
caenorhabditis_elegans		WBGENE00013043
caenorhabditis_elegans		WBGENE00014161
caenorhabditis_elegans		WBGENE00018060
caenorhabditis_elegans		WBGENE00018061
caenorhabditis_elegans		WBGENE00020612

Paralogs (5): ARRDC2 (ENSG00000105643), ARRDC4 (ENSG00000140450), ARRDC1 (ENSG00000197070), ARRDC5 (ENSG00000205784), TXNIP (ENSG00000265972)

Protein

Protein identifiers

Arrestin domain-containing protein 3 — Q96B67 (reviewed: Q96B67)

Alternative names: TBP-2-like inducible membrane protein

All UniProt accessions (1): Q96B67

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors. Plays a role in NEDD4-mediated ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2 degradation. May recruit NEDD4 to ADRB2. Alternatively, may function as adapter protein that does not play a major role in recruiting NEDD4 to ADRB2, but rather plays a role in a targeting ADRB2 to endosomes.

Subunit / interactions. Interacts (via PPxY motifs) with NEDD4 (via WW domains). Interacts with ADRB2. Interacts with ADRB3. Interacts with HGS (via PPxY motifs). Does not bind TXN (thioredoxin). Interacts with ITCH. Interacts with WWP1 (via WW domains).

Subcellular location. Cytoplasm. Cell membrane. Lysosome. Endosome. Early endosome.

Tissue specificity. Highly expressed in skeletal muscle, placenta, kidney, lung, liver, blood, adrenal gland, lymph node, mammary gland, thyroid, and trachea. Very low levels in colon, thymus, spleen, small intestine, bladder and bone marrow. Strong expression in differentiated adipocytes compared to preadipocytes. Detected in omental fat and subcutaneous fat tissue.

Induction. By troglitazone and pioglitazone (selective PPARG agonists), by prostaglandin J2 (PGJ2) and by L165,041 (a PPARD ligand), by vitamin D3 and, to a lesser extent, by phorbol myristate acetate (PMA) in the promyelocytic leukemia HL-60 cells. No induction by retinoic acid, nor by clofibrate (a specific PPARA agonist). Up-regulated by fasting.

Similarity. Belongs to the arrestin family.

RefSeq proteins (4): NP_001316599, NP_001316600, NP_001316601, NP_065852* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011021	Arrestin-like_N	Domain
IPR011022	Arrestin-like_C	Domain
IPR014752	Arrestin-like_C_sf	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR050357	Arrestin_domain-protein	Family

Pfam: PF00339, PF02752

UniProt features (25 total): mutagenesis site 10, strand 8, short sequence motif 2, chain 1, region of interest 1, sequence conflict 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4N7H	X-RAY DIFFRACTION	1.7
4R7V	X-RAY DIFFRACTION	1.73
4R7X	X-RAY DIFFRACTION	2.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B67-F1	82.36	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (10):

Position	Phenotype
135	nearly abolishes interaction with adrb2; when associated with e-56; e-58 and e-153.
139	abolishes interaction with adrb2; when associated with e-48; e-52 and e-85.
153	nearly abolishes interaction with adrb2; when associated with e-56; e-58 and e-135.
346–349	strongly reduces interaction with nedd4. abolishes interaction with nedd4; when associated with 391-a–a-394. abolishes
391–394	abolishes interaction with nedd4; when associated with 346-a–a-349.
48	abolishes interaction with adrb2; when associated with e-52; e-85 and e-139.
52	abolishes interaction with adrb2; when associated with e-48; e-85 and e-139.
56	nearly abolishes interaction with adrb2; when associated with e-58; e-135 and e-153.
58	nearly abolishes interaction with adrb2; when associated with e-56; e-135 and e-153.
85	abolishes interaction with adrb2; when associated with e-48; e-52 and e-139.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 382 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RRAGTTGT_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, NKX25_02, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, AREB6_01, GOBP_REGULATION_OF_HEAT_GENERATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, TAL1ALPHAE47_01, GOBP_HIPPO_SIGNALING, FOXO4_01, CACCAGC_MIR138

GO Biological Process (11): protein transport (GO:0015031), heat generation (GO:0031649), negative regulation of heat generation (GO:0031651), positive regulation of hippo signaling (GO:0035332), skin development (GO:0043588), positive regulation of ubiquitin-protein transferase activity (GO:0051443), fat pad development (GO:0060613), negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071878), negative regulation of locomotion involved in locomotory behavior (GO:0090327), negative regulation of cold-induced thermogenesis (GO:0120163), temperature homeostasis (GO:0001659)

GO Molecular Function (2): beta-3 adrenergic receptor binding (GO:0031699), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), early endosome (GO:0005769), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of multicellular organismal process	2
cellular anatomical structure	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
temperature homeostasis	1
heat generation	1
regulation of heat generation	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
animal organ development	1
ubiquitin-protein transferase activity	1
positive regulation of protein ubiquitination	1
positive regulation of catalytic activity	1
regulation of ubiquitin-protein transferase activity	1
adipose tissue development	1
adenylate cyclase-activating adrenergic receptor signaling pathway	1
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
locomotion involved in locomotory behavior	1
negative regulation of locomotion	1
negative regulation of behavior	1
regulation of locomotion involved in locomotory behavior	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
multicellular organismal-level homeostasis	1
adrenergic receptor binding	1
binding	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARRDC3	NEDD4	P46934	945
ARRDC3	WWP2	O00308	795
ARRDC3	ARRB1	P49407	782
ARRDC3	SAG	P10523	701
ARRDC3	TXN	P10599	695
ARRDC3	ADRB2	P07550	645
ARRDC3	WWP1	Q9H0M0	562
ARRDC3	LYSMD3	Q7Z3D4	515
ARRDC3	PPARG	P37231	507
ARRDC3	ERGIC1	Q969X5	504
ARRDC3	AKT1	P31749	434
ARRDC3	PCYOX1L	Q8NBM8	428
ARRDC3	VPS9D1	Q9Y2B5	427
ARRDC3	ARRB2	P32121	416
ARRDC3	RPUSD2	Q8IZ73	413

IntAct

194 interactions, top by confidence:

A	B	Type	Score
ARRDC3	ITCH	psi-mi:“MI:0915”(physical association)	0.820
ARRDC3	WWP1	psi-mi:“MI:0915”(physical association)	0.800
ARRDC3	NEDD4	psi-mi:“MI:0403”(colocalization)	0.790
ARRDC3	NEDD4	psi-mi:“MI:0915”(physical association)	0.790
WWP2	ARRDC3	psi-mi:“MI:0915”(physical association)	0.770
ARRDC3	NEDD4L	psi-mi:“MI:0915”(physical association)	0.770
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
HPGDS	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	BAG3	psi-mi:“MI:0915”(physical association)	0.720
STAM2	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP3	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	OTUB2	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	DCUN1D1	psi-mi:“MI:0915”(physical association)	0.720
UBE2E2	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	HPGDS	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	STAM2	psi-mi:“MI:0915”(physical association)	0.720
OTUB2	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	UBE2E2	psi-mi:“MI:0915”(physical association)	0.720
BAG3	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
DCUN1D1	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (290): ARRDC3 (Affinity Capture-Western), ARRDC3 (Two-hybrid), ARRDC3 (Two-hybrid), ARRDC3 (Two-hybrid), ARRDC3 (Two-hybrid), ARRDC3 (Two-hybrid), ARRDC3 (Two-hybrid), ARRDC3 (Two-hybrid), OTUB2 (Two-hybrid), TRIM42 (Two-hybrid), ADRB2 (Affinity Capture-Western), ADRB3 (Affinity Capture-Western), ADRB2 (Affinity Capture-Western), HGS (Affinity Capture-Western), ARRDC3 (Affinity Capture-Western)

ESM2 similar proteins: A0A0B4J1F4, A6NEK1, G3X9X1, O14972, O15344, O15519, O35075, O70263, O70583, O94955, P82457, P82458, Q2HY40, Q2TBA3, Q32KX1, Q32NJ2, Q497K5, Q4VX76, Q54DI8, Q568M3, Q5M7W1, Q5R5L7, Q5R811, Q5R8Q5, Q5RD56, Q5RDY3, Q5RF33, Q60584, Q62807, Q6TXF1, Q6ZWE6, Q7TP90, Q7TPQ9, Q7ZX59, Q80WG7, Q8BG60, Q8BM47, Q8IY47, Q8NCT1, Q8W4D4

Diamond homologs: A0A0B4J1F4, Q0VCA2, Q2HY40, Q5M7W1, Q5R5L7, Q5R811, Q6TXF1, Q7TP90, Q7TPQ9, Q8BG60, Q8NCT1, Q8TBH0, Q96B67, Q9D668, Q9H3M7, O45782, Q99KN1, Q02805

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
Negative regulators of DDX58/IFIH1 signaling	5	38.8×	2e-05
Ovarian tumor domain proteases	5	33.2×	3e-05
Regulation of TNFR1 signaling	6	32.0×	7e-06
Cargo recognition for clathrin-mediated endocytosis	6	15.0×	2e-04
Clathrin-mediated endocytosis	5	10.2×	3e-03
Antigen processing: Ubiquitination & Proteasome degradation	10	8.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein monoubiquitination	6	44.9×	2e-06
protein K63-linked ubiquitination	5	29.1×	8e-05
protein K48-linked ubiquitination	7	25.6×	2e-06
ubiquitin-dependent protein catabolic process	7	11.3×	2e-04
protein ubiquitination	10	9.0×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

679 predictions. Top by Δscore:

Variant	Effect	Δscore
5:91371453:CAAT:C	acceptor_gain	1.0000
5:91371454:AATC:A	acceptor_loss	1.0000
5:91371457:C:CC	acceptor_gain	1.0000
5:91373682:A:AC	donor_gain	1.0000
5:91373682:AC:A	donor_gain	1.0000
5:91373682:ACCT:A	donor_gain	1.0000
5:91373683:C:CC	donor_gain	1.0000
5:91373683:CC:C	donor_gain	1.0000
5:91373683:CCT:C	donor_gain	1.0000
5:91373683:CCTC:C	donor_gain	1.0000
5:91373683:CCTCT:C	donor_gain	1.0000
5:91373834:TGGTG:T	acceptor_gain	1.0000
5:91373835:GGTG:G	acceptor_gain	1.0000
5:91373836:GTG:G	acceptor_gain	1.0000
5:91373837:TG:T	acceptor_gain	1.0000
5:91373839:C:CC	acceptor_gain	1.0000
5:91374177:CA:C	donor_gain	1.0000
5:91374274:TACCT:T	acceptor_loss	1.0000
5:91374277:C:A	acceptor_loss	1.0000
5:91374278:T:A	acceptor_loss	1.0000
5:91374918:ATACC:A	donor_loss	1.0000
5:91374920:A:AC	donor_gain	1.0000
5:91374921:C:CC	donor_gain	1.0000
5:91374950:C:CT	donor_gain	1.0000
5:91374951:T:TT	donor_gain	1.0000
5:91375067:T:TA	donor_gain	1.0000
5:91375174:TTCAC:T	acceptor_gain	1.0000
5:91375175:TCAC:T	acceptor_gain	1.0000
5:91375176:CAC:C	acceptor_gain	1.0000
5:91375176:CACC:C	acceptor_gain	1.0000

AlphaMissense

2707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:91374218:C:A	G310V	1.000
5:91374218:C:T	G310D	1.000
5:91374219:C:G	G310R	1.000
5:91375163:A:T	I210K	1.000
5:91375522:C:T	G201D	1.000
5:91375523:C:G	G201R	1.000
5:91375540:G:T	A195D	1.000
5:91376658:A:T	V158D	1.000
5:91376664:A:G	F156S	1.000
5:91376736:C:T	G132D	1.000
5:91376737:C:G	G132R	1.000
5:91382916:C:A	W59C	1.000
5:91382916:C:G	W59C	1.000
5:91382917:C:G	W59S	1.000
5:91382918:A:G	W59R	1.000
5:91382918:A:T	W59R	1.000
5:91382935:C:T	G53E	1.000
5:91382998:C:T	G32E	1.000
5:91383004:A:T	V30D	1.000
5:91374215:G:A	T311I	0.999
5:91374227:A:G	L307P	0.999
5:91374227:A:T	L307H	0.999
5:91374926:A:G	L289P	0.999
5:91374933:A:C	Y287D	0.999
5:91374952:A:C	C280W	0.999
5:91374965:G:A	S276F	0.999
5:91375005:A:G	W263R	0.999
5:91375005:A:T	W263R	0.999
5:91375103:T:G	Q230P	0.999
5:91375144:G:C	N216K	0.999

dbSNP variants (sampled 300 via entrez): RS1000032233 (5:91370017 G>A), RS1000131206 (5:91370305 A>G,T), RS1000206648 (5:91370708 A>G), RS1000238525 (5:91377351 C>T), RS1000330807 (5:91378020 TAAA>T,TAAAA), RS1000413086 (5:91378241 A>G), RS1000920111 (5:91382497 A>G), RS1001018193 (5:91383747 A>G), RS1001223465 (5:91383481 G>A), RS1001407810 (5:91377253 C>T), RS1001562462 (5:91368837 T>C), RS1001604623 (5:91377987 A>G), RS1001733144 (5:91376935 T>G), RS1001898041 (5:91370511 T>G), RS1002036049 (5:91369901 C>T)

Disease associations

OMIM: gene MIM:612464 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001521_5	Subcutaneous adipose tissue	8.000000e-06
GCST001816_3	Breast cancer (prognosis)	1.000000e-06
GCST002537_2	Breast cancer	2.000000e-09
GCST002727_3	Breast cancer (survival)	1.000000e-06
GCST004988_188	Breast cancer	5.000000e-11
GCST90002401_21	Platelet distribution width	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	6
bisphenol A	affects expression, increases expression	3
(+)-JQ1 compound	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance	3
Formaldehyde	increases expression	3
Smoke	decreases expression, increases abundance	3
potassium chromate(VI)	affects cotreatment, increases expression, decreases expression	2
Arsenic Trioxide	increases expression	2
Ethanol	affects cotreatment, increases expression	2
Cisplatin	decreases expression, increases expression	2
Estradiol	decreases expression	2
Oxygen	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	decreases expression	1
resorcinol	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2M4	Abcam A-549 ARRDC3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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