ARRDC2

Summary

ARRDC2 (arrestin domain containing 2, HGNC:25225) is a protein-coding gene on chromosome 19p13.11, encoding Arrestin domain-containing protein 2 (Q8TBH0).

Predicted to be involved in protein transport. Located in cytoplasmic vesicle and plasma membrane.

Source: NCBI Gene 27106 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• MANE Select transcript: NM_015683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25225
Approved symbol	ARRDC2
Name	arrestin domain containing 2
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	CLONE24945, PP2703
Ensembl gene	ENSG00000105643
Ensembl biotype	protein_coding
Entrez	27106

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000222250, ENST00000379656, ENST00000593460, ENST00000593560, ENST00000594411, ENST00000595712, ENST00000596105, ENST00000600788, ENST00000608009, ENST00000683912, ENST00000861324, ENST00000861325, ENST00000861326, ENST00000861327, ENST00000861328, ENST00000861329, ENST00000861330, ENST00000861331, ENST00000861332, ENST00000969595, ENST00000969596, ENST00000969597, ENST00000969598, ENST00000969599

RefSeq mRNA: 3 — MANE Select: NM_015683 NM_001025604, NM_001286826, NM_015683

CCDS: CCDS12370, CCDS32956

Canonical transcript exons

ENST00000222250 — 8 exons

Exon	Start	End
ENSE00000689925	18010572	18010729
ENSE00001125835	18008170	18008584
ENSE00003152102	18012913	18014102
ENSE00003493177	18009783	18010039
ENSE00003507456	18010196	18010358
ENSE00003543686	18008711	18008777
ENSE00003703967	18008971	18009118
ENSE00003707213	18009592	18009694

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7984 / max 271.3708, expressed in 1631 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174577	4.1427	624
174573	4.0391	1387
174574	1.6165	451
174575	0.9769	299
174572	0.4457	190
174571	0.2310	65
208729	0.1647	72
174576	0.1064	49
208728	0.0755	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	98.28	gold quality
granulocyte	CL:0000094	97.39	gold quality
gastrocnemius	UBERON:0001388	97.24	gold quality
muscle of leg	UBERON:0001383	96.69	gold quality
tibial artery	UBERON:0007610	96.18	gold quality
popliteal artery	UBERON:0002250	96.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.03	gold quality
descending thoracic aorta	UBERON:0002345	95.89	gold quality
upper lobe of left lung	UBERON:0008952	95.76	gold quality
aorta	UBERON:0000947	95.75	gold quality
peripheral nervous system	UBERON:0000010	95.36	gold quality
tibial nerve	UBERON:0001323	95.36	gold quality
left coronary artery	UBERON:0001626	95.34	gold quality
thoracic aorta	UBERON:0001515	95.33	gold quality
ascending aorta	UBERON:0001496	95.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.08	gold quality
coronary artery	UBERON:0001621	95.00	gold quality
upper lobe of lung	UBERON:0008948	94.97	gold quality
right coronary artery	UBERON:0001625	94.93	gold quality
spleen	UBERON:0002106	94.76	gold quality
left lobe of thyroid gland	UBERON:0001120	94.62	gold quality
mucosa of stomach	UBERON:0001199	94.56	gold quality
lymph node	UBERON:0000029	94.39	gold quality
spinal cord	UBERON:0002240	94.20	gold quality
right lobe of thyroid gland	UBERON:0001119	94.04	gold quality
tibialis anterior	UBERON:0001385	93.80	silver quality
minor salivary gland	UBERON:0001830	93.73	gold quality
endocervix	UBERON:0000458	93.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.33
E-ENAD-17	no	56.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting ARRDC2, 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-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-301A-5P	96.88	68.07	931

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	arrdc2	ENSDARG00000020761
mus_musculus	Arrdc2	ENSMUSG00000002910
rattus_norvegicus	Arrdc2	ENSRNOG00000019009
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): ARRDC3 (ENSG00000113369), ARRDC4 (ENSG00000140450), ARRDC1 (ENSG00000197070), ARRDC5 (ENSG00000205784), TXNIP (ENSG00000265972)

Protein

Protein identifiers

Arrestin domain-containing protein 2 — Q8TBH0 (reviewed: Q8TBH0)

All UniProt accessions (3): Q8TBH0, A0A804HLL9, V9GYU7

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with WWP1 (via WW domains).

Similarity. Belongs to the arrestin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TBH0-1	1	yes
Q8TBH0-2	2

RefSeq proteins (3): NP_001020775, NP_001273755, NP_056498* (*=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 (6 total): sequence variant 4, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBH0-F1	81.70	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GGGCATT_MIR365, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_MYOTUBE_DIFFERENTIATION, NOUZOVA_METHYLATED_IN_APL, GOBP_RESPONSE_TO_MECHANICAL_STIMULUS, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, GOBP_MUSCLE_CELL_DIFFERENTIATION, chr19p13, GOTTWEIN_TARGETS_OF_KSHV_MIR_K12_11, DODD_NASOPHARYNGEAL_CARCINOMA_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP

GO Biological Process (1): protein transport (GO:0015031)

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

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARRDC2	TMA16	Q96EY4	491
ARRDC2	SYDE2	Q5VT97	481
ARRDC2	RASL11B	Q9BPW5	443
ARRDC2	CNKSR1	Q969H4	433
ARRDC2	ZCCHC24	Q8N2G6	428
ARRDC2	RAB3A	P20336	425
ARRDC2	RHOF	Q9HBH0	418
ARRDC2	MROH7	Q68CQ1	414
ARRDC2	TRIB1	Q96RU8	406
ARRDC2	SSPN	Q14714	404
ARRDC2	RUBCNL	Q9H714	396
ARRDC2	TIGD4	Q8IY51	393
ARRDC2	PHACTR3	Q96KR7	388
ARRDC2	SAG	P10523	385
ARRDC2	GTPBP4	Q9BZE4	377

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ARRDC2	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
EPN2	ARRDC2	psi-mi:“MI:0915”(physical association)	0.560
ARRDC2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
WWP1	TP73	psi-mi:“MI:0914”(association)	0.350
IMPDH1	MGST3	psi-mi:“MI:0914”(association)	0.350
ARRDC2	EPN2	psi-mi:“MI:0915”(physical association)	0.000
ARRDC2	ZRANB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): ARRDC2 (Two-hybrid), ARRDC2 (Two-hybrid), ARRDC2 (Affinity Capture-MS), ARRDC2 (Affinity Capture-MS), ARRDC2 (Affinity Capture-MS), ARRDC2 (Negative Genetic), ARRDC2 (Affinity Capture-RNA), ZSWIM8 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PRKAR1A (Affinity Capture-MS), PJA1 (Affinity Capture-MS), PJA2 (Affinity Capture-MS), BAG6 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), POLR2A (Affinity Capture-MS)

ESM2 similar proteins: E2RDP2, O14526, O14558, O15197, O35878, O95382, P02512, P04792, P0C0K6, P0C5W1, P14602, P15991, P42929, P42930, P97541, Q00649, Q08DM2, Q13470, Q148F8, Q16082, Q2KHU9, Q2KIR4, Q3T033, Q3T149, Q4VYA0, Q5EBG6, Q5JR98, Q5JZY3, Q5RE82, Q5S1U1, Q6F5E8, Q6NY19, Q6P9Q4, Q6SJQ8, Q6ZW31, Q8C052, Q8CDY7, Q8N5L8, Q8TBH0, Q8TDZ2

Diamond homologs: A0A0B4J1F4, Q0VCA2, Q2HY40, Q5M7W1, Q5R5L7, Q5R811, Q6TXF1, Q7TP90, Q7TPQ9, Q8BG60, Q8NCT1, Q8TBH0, Q96B67, Q9D668, Q9H3M7, O45782, Q497K5, Q99KN1, Q02805

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	70
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
60074	GRCh38/hg38 19p13.11(chr19:17922234-18463153)x1	Pathogenic

SpliceAI

667 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18008773:CCCCC:C	donor_gain	1.0000
19:18008775:CCC:C	donor_gain	1.0000
19:18008778:G:GG	donor_gain	1.0000
19:18008968:TA:T	acceptor_loss	1.0000
19:18008969:A:AG	acceptor_gain	1.0000
19:18008969:AG:A	acceptor_gain	1.0000
19:18008969:AGGA:A	acceptor_loss	1.0000
19:18008970:G:GA	acceptor_loss	1.0000
19:18008970:G:GG	acceptor_gain	1.0000
19:18008970:GG:G	acceptor_gain	1.0000
19:18008970:GGACC:G	acceptor_gain	1.0000
19:18009115:GCTG:G	donor_gain	1.0000
19:18009117:TG:T	donor_gain	1.0000
19:18009118:GG:G	donor_gain	1.0000
19:18009119:G:GG	donor_gain	1.0000
19:18009121:GA:G	donor_loss	1.0000
19:18009582:A:AG	acceptor_gain	1.0000
19:18009582:ACACC:A	acceptor_gain	1.0000
19:18009583:C:G	acceptor_gain	1.0000
19:18009584:A:AG	acceptor_gain	1.0000
19:18009584:ACC:A	acceptor_gain	1.0000
19:18009585:C:G	acceptor_gain	1.0000
19:18009586:C:A	acceptor_gain	1.0000
19:18009589:CAGG:C	acceptor_loss	1.0000
19:18009590:A:AG	acceptor_gain	1.0000
19:18009590:AGG:A	acceptor_loss	1.0000
19:18009591:G:GT	acceptor_gain	1.0000
19:18009690:CCCAG:C	donor_loss	1.0000
19:18009691:CCAG:C	donor_loss	1.0000
19:18009692:CAGGT:C	donor_loss	1.0000

AlphaMissense

2589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18009081:T:A	V151D	0.998
19:18008485:T:A	W59R	0.997
19:18008485:T:C	W59R	0.997
19:18009009:T:A	V127D	0.997
19:18009685:T:G	Y195D	0.997
19:18008487:G:C	W59C	0.996
19:18008487:G:T	W59C	0.996
19:18009014:T:G	Y129D	0.996
19:18009075:T:C	F149S	0.996
19:18009665:C:A	A188D	0.996
19:18008987:T:C	F120L	0.995
19:18008989:C:A	F120L	0.995
19:18008989:C:G	F120L	0.995
19:18009677:G:C	R192P	0.995
19:18009978:T:C	I263T	0.995
19:18010254:G:A	G303D	0.995
19:18008985:C:T	S119F	0.994
19:18009653:T:A	V184D	0.994
19:18009792:T:A	I201N	0.994
19:18009804:C:A	A205D	0.994
19:18010035:T:A	L282H	0.994
19:18009003:G:A	G125D	0.993
19:18009798:T:A	V203D	0.993
19:18009869:T:C	F227L	0.993
19:18009871:C:A	F227L	0.993
19:18009871:C:G	F227L	0.993
19:18008486:G:C	W59S	0.992
19:18008759:T:C	F108S	0.992
19:18009021:T:A	I131N	0.992
19:18009676:C:A	R192S	0.991

dbSNP variants (sampled 300 via entrez): RS1000006638 (19:18014097 A>G), RS1000181924 (19:18000697 A>C), RS1000234080 (19:18000588 TGTC>T), RS1000305372 (19:18005568 C>A,T), RS1000376211 (19:18014399 G>A,C), RS1000794531 (19:18008672 C>G,T), RS1001109029 (19:18003294 T>C), RS1001351901 (19:18013408 C>T), RS1001449665 (19:18003796 C>T), RS1001521429 (19:18003617 C>A,T), RS1001587246 (19:18000995 C>T), RS1001638122 (19:18005652 G>A,C), RS1001681815 (19:18000747 T>C,G), RS1001795929 (19:18005851 G>A,T), RS1001855373 (19:18002497 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004608_133	Granulocyte percentage of myeloid white cells	3.000000e-14
GCST004609_96	Monocyte percentage of white cells	1.000000e-14
GCST004625_210	Monocyte count	5.000000e-20
GCST004627_101	Lymphocyte count	2.000000e-10
GCST006979_743	Heel bone mineral density	8.000000e-13
GCST006979_749	Heel bone mineral density	3.000000e-23
GCST90002388_364	Lymphocyte count	2.000000e-14
GCST90002389_398	Lymphocyte percentage of white cells	9.000000e-11
GCST90002393_650	Monocyte count	1.000000e-43
GCST90002394_549	Monocyte percentage of white cells	3.000000e-37
GCST90002399_229	Neutrophil percentage of white cells	1.000000e-14

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0009270	heel bone mineral density
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	affects response to substance	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azathioprine	increases expression	1
Benzene	increases expression	1
Cadmium	decreases expression, increases abundance	1
Carmustine	affects response to substance	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1

Clinical trials (associated diseases)

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