STON1

Summary

STON1 (stonin 1, HGNC:17003) is a protein-coding gene on chromosome 2p16.3, encoding Stonin-1 (Q9Y6Q2). May be involved in the endocytic machinery.

Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. This gene encodes one of two human homologs of the Drosophila melanogaster stoned B protein. This protein is related to components of the endocytic machinery and exhibits a modular structure consisting of an N-terminal proline-rich domain, a central region of homology specific to the human stoned B-like proteins, and a C-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Read-through transcription of this gene into the neighboring downstream gene, which encodes TFIIA-alpha/beta-like factor, generates a transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11037 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_006873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17003
Approved symbol	STON1
Name	stonin 1
Location	2p16.3
Locus type	gene with protein product
Status	Approved
Aliases	SBLF, stoned-b1
Ensembl gene	ENSG00000243244
Ensembl biotype	protein_coding
OMIM	605357
Entrez	11037

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000404752, ENST00000406226, ENST00000444932, ENST00000484110, ENST00000649748, ENST00000871922, ENST00000871923, ENST00000871924, ENST00000871925, ENST00000871926, ENST00000871927, ENST00000964666, ENST00000964667, ENST00000964668, ENST00000964669

RefSeq mRNA: 2 — MANE Select: NM_006873 NM_001198595, NM_006873

CCDS: CCDS1841

Canonical transcript exons

ENST00000404752 — 4 exons

Exon	Start	End
ENSE00001556689	48530154	48530216
ENSE00001561267	48595228	48598513
ENSE00003530448	48580587	48582563
ENSE00003643632	48591653	48591855

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 97.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1225 / max 259.4302, expressed in 1299 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20190	11.8477	1285
20191	0.4999	238
20203	0.3909	156
20193	0.1601	94
20192	0.1533	60
20189	0.0706	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	97.48	gold quality
cauda epididymis	UBERON:0004360	94.44	gold quality
myometrium	UBERON:0001296	93.44	gold quality
mucosa of stomach	UBERON:0001199	92.88	gold quality
hair follicle	UBERON:0002073	92.45	gold quality
calcaneal tendon	UBERON:0003701	92.33	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.27	gold quality
lower esophagus	UBERON:0013473	92.20	gold quality
tibia	UBERON:0000979	92.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.52	gold quality
choroid plexus epithelium	UBERON:0003911	91.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.36	gold quality
lower lobe of lung	UBERON:0008949	91.18	gold quality
periodontal ligament	UBERON:0008266	91.14	gold quality
inferior olivary complex	UBERON:0002127	90.98	gold quality
saphenous vein	UBERON:0007318	90.98	gold quality
body of uterus	UBERON:0009853	89.99	gold quality
urinary bladder	UBERON:0001255	89.83	gold quality
seminal vesicle	UBERON:0000998	89.67	gold quality
colonic epithelium	UBERON:0000397	89.43	gold quality
pericardium	UBERON:0002407	89.19	gold quality
ventricular zone	UBERON:0003053	89.07	gold quality
cranial nerve II	UBERON:0000941	88.95	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.76	gold quality
left uterine tube	UBERON:0001303	88.16	gold quality
renal glomerulus	UBERON:0000074	88.00	gold quality
stromal cell of endometrium	CL:0002255	87.98	gold quality
metanephric glomerulus	UBERON:0004736	87.71	gold quality
gall bladder	UBERON:0002110	87.60	gold quality
parietal pleura	UBERON:0002400	87.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.56
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting STON1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
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-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 3)

• Functional analysis of an homologous Drosophila gene. (PMID:14504226)
• Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome. (PMID:34248847)
• Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma. (PMID:36759775)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	STON1	ENSDARG00000104596
mus_musculus	Ston1	ENSMUSG00000033855
rattus_norvegicus	Ston1	ENSRNOG00000016688

Paralogs (7): AP3M2 (ENSG00000070718), AP1M1 (ENSG00000072958), AP1M2 (ENSG00000129354), STON2 (ENSG00000140022), AP2M1 (ENSG00000161203), AP3M1 (ENSG00000185009), AP4M1 (ENSG00000221838)

Protein

Protein identifiers

Stonin-1 — Q9Y6Q2 (reviewed: Q9Y6Q2)

Alternative names: Stoned B-like factor

All UniProt accessions (2): Q9Y6Q2, H7C1E2

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the endocytic machinery.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Ubiquitous.

Miscellaneous. In contrast to other members of the family, it does not contain NPF (Asn-Pro-Phe) sites and thereby does not interact with EPS15, EPS15R and ITSN1.

Similarity. Belongs to the Stoned B family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y6Q2-1	1	yes
Q9Y6Q2-2	2
Q9Y6Q2-3	3

RefSeq proteins (2): NP_001185524, NP_006864* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012320	SHD_dom	Domain
IPR017110	Stonin	Family
IPR028565	MHD	Domain
IPR036168	AP2_Mu_C_sf	Homologous_superfamily
IPR050431	Adaptor_comp_med_subunit	Family

Pfam: PF00928

UniProt features (14 total): sequence conflict 4, sequence variant 4, domain 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6Q2-F1	65.75	0.27

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 204 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, HORIUCHI_WTAP_TARGETS_DN, BROWNE_HCMV_INFECTION_6HR_DN, TTTGTAG_MIR520D, GOBP_FOCAL_ADHESION_ASSEMBLY, RACCACAR_AML_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_JUNCTION_ORGANIZATION, GOCC_COATED_VESICLE, BROWNE_HCMV_INFECTION_14HR_DN, GOCC_GOLGI_ASSOCIATED_VESICLE, GOCC_VESICLE_COAT

GO Biological Process (9): substrate-dependent cell migration (GO:0006929), regulation of endocytosis (GO:0030100), platelet-derived growth factor receptor signaling pathway (GO:0048008), focal adhesion assembly (GO:0048041), synaptic vesicle endocytosis (GO:0048488), clathrin-dependent endocytosis (GO:0072583), ruffle assembly (GO:0097178), focal adhesion disassembly (GO:0120181), endocytosis (GO:0006897)

GO Molecular Function (2): clathrin-cargo adaptor activity (GO:0035615), cargo adaptor activity (GO:0140312)

GO Cellular Component (7): synaptic vesicle (GO:0008021), AP-2 adaptor complex (GO:0030122), cell leading edge (GO:0031252), cell projection (GO:0042995), cytoplasm (GO:0005737), clathrin-coated pit (GO:0005905), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
vesicle-mediated transport	2
cell migration	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
receptor-mediated endocytosis	1
ruffle organization	1
plasma membrane bounded cell projection assembly	1
cell-substrate junction disassembly	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
clathrin binding	1
cargo adaptor activity	1
protein-macromolecule adaptor activity	1
exocytic vesicle	1
presynapse	1
clathrin coat of endocytic vesicle	1
clathrin adaptor complex	1
clathrin coat of coated pit	1
plasma membrane protein complex	1
intracellular anatomical structure	1
endomembrane system	1
membrane	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STON1	GTF2A1L	Q9UNN4	932
STON1	GTF2A1	P52655	847
STON1	GTF2A2	P52657	814
STON1	PPP1R21	Q6ZMI0	610
STON1	C13orf42	A0A1B0GVH6	593
STON1	STPG4	Q8N801	447
STON1	LCA5L	O95447	431
STON1	Q53S48	Q53S48	404
STON1	KRABD5	Q7Z2F6	400
STON1	OR13J1	Q8NGT2	400
STON1	TMEM247	A6NEH6	394
STON1	FOXN2	P32314	391
STON1	FAM178B	Q8IXR5	377
STON1	SYNGR4	O95473	370
STON1	DEXI	O95424	369

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SRPK2	STON1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
STON1	bipA	psi-mi:“MI:0915”(physical association)	0.370
FGFR4	SH3PXD2B	psi-mi:“MI:2364”(proximity)	0.270
fsR	STON1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): STON1 (Affinity Capture-MS), STON1 (Proximity Label-MS), STON1 (Affinity Capture-RNA), STON1-GTF2A1L (Proximity Label-MS), STON1 (Proximity Label-MS), STON1 (Proximity Label-MS), STON1 (Proximity Label-MS), STON1-GTF2A1L (Proximity Label-MS), STON1 (Affinity Capture-RNA), STON1 (Proximity Label-MS), STON1 (Proximity Label-MS), STON1 (Proximity Label-MS), STON1 (Proximity Label-MS), STON1-GTF2A1L (Affinity Capture-MS), STON1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A571BF63, A2BF66, A6QQY4, B0UYH6, D3ZWE7, E2QXH7, F6RRD7, O60566, O88665, P23611, P38531, Q05B18, Q08DB0, Q0P4I1, Q28IH8, Q2KIY6, Q3B7T8, Q3U1T9, Q3UB74, Q3YBR2, Q4R8B9, Q5HZK1, Q5I0E6, Q5JTW2, Q5M7C8, Q5PQK8, Q5PQQ9, Q5R789, Q5RA37, Q5SQP1, Q5XIZ9, Q66IH2, Q6IQY5, Q6NZY4, Q7T0S7, Q7Z3E5, Q86VD1, Q86X24, Q8BMD7, Q8C5W4

Diamond homologs: D4AB66, P90761, Q24212, Q8BZ60, Q8CDJ8, Q8WXE9, Q9Y6Q2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1128 predictions. Top by Δscore:

Variant	Effect	Δscore
2:48582564:G:GG	donor_gain	1.0000
2:48595380:AG:A	donor_gain	1.0000
2:48530214:CCGG:C	donor_loss	0.9900
2:48530215:CGGTG:C	donor_loss	0.9900
2:48530216:GGTG:G	donor_loss	0.9900
2:48530217:GTG:G	donor_loss	0.9900
2:48530218:TGAG:T	donor_loss	0.9900
2:48530219:GAGT:G	donor_loss	0.9900
2:48580585:A:AG	acceptor_gain	0.9900
2:48580586:G:GG	acceptor_gain	0.9900
2:48580586:GA:G	acceptor_gain	0.9900
2:48595298:A:AG	donor_gain	0.9900
2:48595299:G:GG	donor_gain	0.9900
2:48595301:AGG:A	donor_gain	0.9900
2:48595379:TA:T	donor_gain	0.9900
2:48597283:ATCT:A	acceptor_gain	0.9900
2:48530016:G:GT	donor_gain	0.9800
2:48530017:G:T	donor_gain	0.9800
2:48530030:G:T	donor_gain	0.9800
2:48530213:GCCG:G	donor_gain	0.9800
2:48530217:G:GG	donor_gain	0.9800
2:48595224:ACAGG:A	acceptor_loss	0.9800
2:48595225:CAGGT:C	acceptor_loss	0.9800
2:48595226:A:T	acceptor_loss	0.9800
2:48595227:G:A	acceptor_loss	0.9800
2:48595300:TAG:T	donor_gain	0.9800
2:48597286:T:TA	acceptor_gain	0.9800
2:48530702:T:A	acceptor_gain	0.9700
2:48530702:T:TA	acceptor_gain	0.9700
2:48580584:CA:C	acceptor_loss	0.9700

AlphaMissense

4851 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:48581513:T:A	W294R	0.999
2:48581513:T:C	W294R	0.999
2:48582530:T:A	W633R	0.999
2:48582530:T:C	W633R	0.999
2:48581475:G:C	R281T	0.998
2:48581476:A:C	R281S	0.998
2:48581476:A:T	R281S	0.998
2:48581515:G:C	W294C	0.998
2:48581515:G:T	W294C	0.998
2:48582521:G:C	A630P	0.998
2:48581481:C:A	P283H	0.997
2:48581764:G:C	K377N	0.997
2:48581764:G:T	K377N	0.997
2:48581768:G:T	G379W	0.997
2:48582365:T:A	W578R	0.997
2:48582365:T:C	W578R	0.997
2:48581472:T:C	L280P	0.996
2:48581480:C:T	P283S	0.996
2:48581508:G:C	R292P	0.996
2:48581769:G:A	G379E	0.996
2:48582492:G:A	G620E	0.996
2:48581507:C:G	R292G	0.995
2:48581762:A:G	K377E	0.995
2:48582261:T:C	L543P	0.995
2:48582354:T:A	V574D	0.995
2:48582491:G:A	G620R	0.995
2:48582491:G:C	G620R	0.995
2:48582491:G:T	G620W	0.995
2:48582498:C:A	A622E	0.995
2:48582531:G:C	W633S	0.995

dbSNP variants (sampled 300 via entrez): RS1000139741 (2:48568896 G>A), RS1000195807 (2:48580396 A>G), RS1000233075 (2:48583602 G>C), RS1000278408 (2:48588552 T>C), RS1000306607 (2:48578741 C>A), RS1000317301 (2:48573539 A>T), RS1000356823 (2:48578490 C>G), RS1000382643 (2:48561742 T>A,C), RS1000420985 (2:48547980 A>G), RS1000421429 (2:48539582 A>C,T), RS1000433683 (2:48575131 G>A), RS1000469872 (2:48549687 C>G,T), RS1000474805 (2:48548364 C>G), RS1000512020 (2:48582845 G>A), RS1000579236 (2:48541854 T>A)

Disease associations

OMIM: gene MIM:605357 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002337_73	Amyotrophic lateral sclerosis (sporadic)	3.000000e-06
GCST003944_26	Hepcidin/ferritin ratio	5.000000e-06
GCST003998_16	Joint mobility (Beighton score)	1.000000e-07
GCST004813_1	Laterality in neovascular age-related macular degeneration	3.000000e-08
GCST006976_124	Macular thickness	2.000000e-10
GCST007323_35	Risk-taking tendency (4-domain principal component model)	2.000000e-08
GCST007978_1	Postoperative atrial fibrillation after cardiac surgery	7.000000e-07
GCST008161_69	Waist circumference adjusted for body mass index	7.000000e-06
GCST009028_37	Adverse response to drug	1.000000e-07
GCST010241_343	Apolipoprotein A1 levels	4.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007901	hepcidin:ferritin ratio
EFO:0007905	joint hypermobility measurement
EFO:0008372	laterality measurement
EFO:0008579	risk-taking behaviour
EFO:0009951	response to surgery
EFO:0009952	post-operative atrial fibrillation
EFO:0007789	BMI-adjusted waist circumference
EFO:0009658	adverse effect
EFO:0004614	apolipoprotein A 1 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	7
trichostatin A	affects cotreatment, decreases expression, increases expression	4
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
vanadyl sulfate	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Panobinostat	affects cotreatment, affects expression	1
Benzo(a)pyrene	increases mutagenesis	1
Calcitriol	decreases expression	1
Cisplatin	affects expression, affects cotreatment	1
Cytarabine	decreases expression	1
Estradiol	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis