ARPIN

Summary

ARPIN (actin related protein 2/3 complex inhibitor, HGNC:28782) is a protein-coding gene on chromosome 15q26.1, encoding Arpin (Q7Z6K5). Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors.

Involved in directional locomotion; negative regulation of cell migration; and negative regulation of cellular component organization. Predicted to be located in lamellipodium.

Source: NCBI Gene 348110 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_182616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28782
Approved symbol	ARPIN
Name	actin related protein 2/3 complex inhibitor
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC61550
Ensembl gene	ENSG00000242498
Ensembl biotype	protein_coding
OMIM	615543
Entrez	348110

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357484, ENST00000460685, ENST00000560096, ENST00000969751

RefSeq mRNA: 2 — MANE Select: NM_182616 NM_001282380, NM_182616

CCDS: CCDS42080, CCDS73780

Canonical transcript exons

ENST00000357484 — 6 exons

Exon	Start	End
ENSE00001599145	89912744	89912952
ENSE00001819260	89895006	89901803
ENSE00003468069	89903216	89903379
ENSE00003519037	89908280	89908412
ENSE00003528670	89910744	89910819
ENSE00003590602	89903777	89903983

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 92.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.9081 / max 33.9493, expressed in 1025 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151551	8.6583	1543
151550	1.9081	1025

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	92.17	gold quality
corpus epididymis	UBERON:0004359	88.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.27	gold quality
colonic epithelium	UBERON:0000397	88.11	gold quality
synovial joint	UBERON:0002217	87.84	gold quality
seminal vesicle	UBERON:0000998	87.70	gold quality
colonic mucosa	UBERON:0000317	87.63	gold quality
urethra	UBERON:0000057	87.42	gold quality
heart right ventricle	UBERON:0002080	86.66	gold quality
pancreas	UBERON:0001264	86.47	gold quality
caput epididymis	UBERON:0004358	86.31	gold quality
nipple	UBERON:0002030	86.12	gold quality
jejunal mucosa	UBERON:0000399	85.96	gold quality
penis	UBERON:0000989	85.92	gold quality
rectum	UBERON:0001052	85.66	gold quality
jejunum	UBERON:0002115	85.48	gold quality
cauda epididymis	UBERON:0004360	85.01	gold quality
mammalian vulva	UBERON:0000997	84.86	gold quality
skin of hip	UBERON:0001554	84.84	gold quality
medial globus pallidus	UBERON:0002477	84.41	gold quality
vena cava	UBERON:0004087	84.25	gold quality
duodenum	UBERON:0002114	84.20	gold quality
layer of synovial tissue	UBERON:0007616	84.13	gold quality
monocyte	CL:0000576	84.06	gold quality
mononuclear cell	CL:0000842	83.92	gold quality
germinal epithelium of ovary	UBERON:0001304	83.72	gold quality
endometrium	UBERON:0001295	83.57	gold quality
leukocyte	CL:0000738	83.52	gold quality
ventricular zone	UBERON:0003053	83.40	gold quality
globus pallidus	UBERON:0001875	83.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.73
E-GEOD-111727	no	161.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting ARPIN, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-2110	99.96	66.68	1930

Literature-anchored findings (GeneRIF, showing 8)

• Arpin protein affects the expression of tight junction proteins and may have an impact on bacterial translocation in severe acute pancreatitis. (PMID:25892881)
• Arpin downregulation may contribute to the initiation and development of breast cancer metastasis. (PMID:26648569)
• Data reveal that Arpin is comprised of an elongated globular core from which the C-terminal tail extends as a linear peptide, thus forming a primary epitope that is readily available to tether Arpin to interacting proteins. (PMID:26774128)
• Low Arpin levels are associated with clinicopathological variables and a poor prognosis in gastric cancer patients (PMID:28293092)
• ARPIN is down-regulated in breast cancer cells and predicts poor prognosis in breast cancer patients. Data suggest that restoration of ARPIN in breast cancer cells suppresses cell proliferation, colony formation, cell cycle distribution, invasion in vitro, and tumorigenesis in vivo (xenograft experiments in nude mice); Arpin acts as tumor suppressor in breast cancer and is associated with inhibition of Akt signaling. (PMID:28531800)
• Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus. (PMID:31721415)
• Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex. (PMID:33923443)
• RNA Editing Enzyme ADAR1 Suppresses the Mobility of Cancer Cells via ARPIN. (PMID:36921992)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arpin	ENSDARG00000041085
mus_musculus	Arpin	ENSMUSG00000039043
rattus_norvegicus	Arpin	ENSRNOG00000014589

Protein

Protein identifiers

Arpin — Q7Z6K5 (reviewed: Q7Z6K5)

Alternative names: Arp2/3 inhibition protein

All UniProt accessions (3): Q7Z6K5, H0YL03, H0YMP5

UniProt curated annotations — full annotation on UniProt →

Function. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence.

Subunit / interactions. Associates with the Arp2/3 complex. Interacts with ARPC2; enhanced by activated RAC1. Interacts with ARPC5; the interaction is dependent on RAC1.

Subcellular location. Cell projection. Lamellipodium.

Domain organisation. The acidic C-terminus is necessary and sufficient to inhibit ARP2/3 complex activity.

Miscellaneous. Based on a naturally occurring readthrough transcript which produces a C15orf38-AP3S2 fusion protein.

Similarity. Belongs to the Arpin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6K5-1	1	yes
Q7Z6K5-2	C15orf38-AP3S2

RefSeq proteins (2): NP_001269309, NP_872422* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018889	Arpin	Family

Pfam: PF10574

UniProt features (7 total): helix 2, strand 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4Z68	X-RAY DIFFRACTION	1.86
7JPN	ELECTRON MICROSCOPY	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6K5-F1	74.31	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_MUSCLE_CONTRACTION, GOBP_ACTIN_FILAMENT_ORGANIZATION, HNF4_01, GOBP_NEGATIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_LAMELLIPODIUM_ORGANIZATION, GOBP_REGULATION_OF_LAMELLIPODIUM_ORGANIZATION

GO Biological Process (4): negative regulation of cell migration (GO:0030336), directional locomotion (GO:0033058), negative regulation of actin nucleation (GO:0051126), negative regulation of lamellipodium morphogenesis (GO:2000393)

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

GO Cellular Component (2): lamellipodium (GO:0030027), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
locomotion	1
actin nucleation	1
regulation of actin nucleation	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
negative regulation of developmental process	1
lamellipodium morphogenesis	1
negative regulation of lamellipodium organization	1
regulation of lamellipodium morphogenesis	1
binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARPIN	AP1AR	Q63HQ0	513
ARPIN	TNKS2	Q9H2K2	499
ARPIN	GMFG	O60234	388
ARPIN	WDR1	O75083	388
ARPIN	PICK1	Q9NRD5	381
ARPIN	AP3S2	P59780	370
ARPIN	ANKRD45	Q5TZF3	366
ARPIN	TWF1	Q12792	357
ARPIN	FAM174C	Q9BVV8	351
ARPIN	WHAMM	Q8TF30	350
ARPIN	ACTR8	Q9H981	343
ARPIN	ARPC2	O15144	342
ARPIN	CORO1B	Q9BR76	342
ARPIN	GAK	O14976	339
ARPIN	AP3D1	O14617	333

IntAct

25 interactions, top by confidence:

A	B	Type	Score
TRIM27	ARPIN	psi-mi:“MI:0915”(physical association)	0.560
ARPIN	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
NIF3L1	ARPIN	psi-mi:“MI:0915”(physical association)	0.560
ARPIN	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
AP4M1		psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PPA2	H1-3	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
PPA2	CLUH	psi-mi:“MI:0914”(association)	0.350
AZU1	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
RAE1	NHERF1	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
ARPIN	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): ARPIN (Two-hybrid), ARPIN (Two-hybrid), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Proximity Label-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-MS), ARPIN (Affinity Capture-RNA), C15orf38-AP3S2 (Affinity Capture-RNA)

ESM2 similar proteins: A0MZE7, A1BF34, A4IN50, A4YM47, A5VS09, A6WYD2, A9BXA2, A9M752, A9WWC9, B0U151, B2S793, B3E9W7, B3PWJ0, B3QKU1, B5ZYL4, B9JD44, B9JG75, C0RES0, C5D2K6, C9DG08, C9DG80, E1XT70, E1XTK3, I6WJ72, P0DW82, P11353, P19239, P21700, P22850, P39374, Q07088, Q08052, Q1LWJ6, Q21PU0, Q27YE3, Q2A068, Q2J0A5, Q2YRK5, Q31IJ9, Q56260

Diamond homologs: Q17QU3, Q1LWJ6, Q66IV5, Q6DJ71, Q7Z6K5, Q9D0A3, Q54F87

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1193 predictions. Top by Δscore:

Variant	Effect	Δscore
15:89908278:A:AC	donor_gain	1.0000
15:89908279:C:CA	donor_gain	1.0000
15:89908313:T:A	donor_gain	1.0000
15:89908408:CGCTC:C	acceptor_gain	1.0000
15:89908410:CTC:C	acceptor_gain	1.0000
15:89908412:CCTG:C	acceptor_loss	1.0000
15:89908413:C:CC	acceptor_gain	1.0000
15:89908413:C:CG	acceptor_loss	1.0000
15:89908420:C:CT	acceptor_gain	1.0000
15:89908421:A:T	acceptor_gain	1.0000
15:89908424:C:CT	acceptor_gain	1.0000
15:89910738:CCTCA:C	donor_loss	1.0000
15:89910739:CTCA:C	donor_loss	1.0000
15:89910739:CTCAC:C	donor_loss	1.0000
15:89910740:TCA:T	donor_loss	1.0000
15:89910740:TCACC:T	donor_loss	1.0000
15:89910741:CACCT:C	donor_loss	1.0000
15:89910742:ACCTT:A	donor_gain	1.0000
15:89910743:C:CA	donor_loss	1.0000
15:89910743:CCTTC:C	donor_gain	1.0000
15:89910746:T:A	donor_gain	1.0000
15:89910746:T:TA	donor_gain	1.0000
15:89910815:TTCCC:T	acceptor_gain	1.0000
15:89910816:TCCC:T	acceptor_gain	1.0000
15:89910817:CCC:C	acceptor_gain	1.0000
15:89910817:CCCC:C	acceptor_gain	1.0000
15:89910818:CC:C	acceptor_gain	1.0000
15:89910818:CCC:C	acceptor_gain	1.0000
15:89910819:CC:C	acceptor_gain	1.0000
15:89910819:CCTG:C	acceptor_loss	1.0000

AlphaMissense

1476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:89903864:A:G	W141R	0.985
15:89903864:A:T	W141R	0.985
15:89908367:G:T	R72S	0.970
15:89908296:G:C	F95L	0.969
15:89908296:G:T	F95L	0.969
15:89908298:A:G	F95L	0.969
15:89903218:A:G	W224R	0.964
15:89903218:A:T	W224R	0.964
15:89903781:G:C	F168L	0.960
15:89903781:G:T	F168L	0.960
15:89903783:A:G	F168L	0.960
15:89903305:A:G	W195R	0.958
15:89903305:A:T	W195R	0.958
15:89908359:G:C	F74L	0.957
15:89908359:G:T	F74L	0.957
15:89908361:A:G	F74L	0.957
15:89910797:C:G	G39R	0.956
15:89910797:C:T	G39R	0.956
15:89903866:A:G	F140S	0.955
15:89912766:A:G	W24R	0.954
15:89912766:A:T	W24R	0.954
15:89903303:C:A	W195C	0.952
15:89903303:C:G	W195C	0.952
15:89903806:A:G	L160P	0.944
15:89903809:C:G	R159P	0.940
15:89903862:C:A	W141C	0.940
15:89903862:C:G	W141C	0.940
15:89903216:C:A	W224C	0.938
15:89903216:C:G	W224C	0.938
15:89908366:C:G	R72P	0.935

dbSNP variants (sampled 300 via entrez): RS1000183807 (15:89908099 G>T), RS1000280472 (15:89897341 C>T), RS1000583711 (15:89914209 G>A), RS1000632537 (15:89895913 G>A), RS1000699869 (15:89896929 T>C), RS1000884036 (15:89898167 A>G), RS1000909513 (15:89912987 A>C,G), RS1001126378 (15:89901402 G>A), RS1001254199 (15:89912178 G>C,T), RS1001446000 (15:89906544 T>A), RS1001497961 (15:89908762 T>A), RS1001802548 (15:89914321 G>A), RS1001828556 (15:89909986 G>A), RS1001875547 (15:89900022 G>C), RS1002175807 (15:89900367 C>A)

Disease associations

OMIM: gene MIM:615543 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007923_29	Medication use (drugs used in diabetes)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009924	Drugs used in diabetes use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
entinostat	decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Arsenicals	increases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Progesterone	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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