SNX9

Summary

SNX9 (sorting nexin 9, HGNC:14973) is a protein-coding gene on chromosome 6q25.3, encoding Sorting nexin-9 (Q9Y5X1). Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis.

This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation.

Source: NCBI Gene 51429 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 68 total
• Druggable target: yes
• MANE Select transcript: NM_016224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14973
Approved symbol	SNX9
Name	sorting nexin 9
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	SH3PX1, SDP1, SH3PXD3A
Ensembl gene	ENSG00000130340
Ensembl biotype	protein_coding
OMIM	605952
Entrez	51429

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 8 retained_intron, 3 nonsense_mediated_decay

ENST00000392185, ENST00000614703, ENST00000614800, ENST00000679691, ENST00000679732, ENST00000679790, ENST00000679814, ENST00000680015, ENST00000680078, ENST00000680089, ENST00000680095, ENST00000680464, ENST00000680495, ENST00000680680, ENST00000680863, ENST00000680974, ENST00000681138, ENST00000681183, ENST00000681186, ENST00000681469, ENST00000681534, ENST00000681651, ENST00000681881, ENST00000902253, ENST00000919905, ENST00000971712, ENST00000971713

RefSeq mRNA: 1 — MANE Select: NM_016224 NM_016224

CCDS: CCDS5253

Canonical transcript exons

ENST00000392185 — 18 exons

Exon	Start	End
ENSE00000830242	157940883	157940974
ENSE00000894243	157935964	157936040
ENSE00000894244	157932195	157932272
ENSE00000894245	157928599	157928702
ENSE00000894246	157927111	157927214
ENSE00000894247	157921531	157921661
ENSE00000894248	157909908	157910025
ENSE00000894249	157909665	157909790
ENSE00000894250	157906128	157906212
ENSE00000894253	157875051	157875176
ENSE00000894254	157873102	157873176
ENSE00001139578	157942791	157945077
ENSE00001218176	157938633	157938747
ENSE00001218186	157937434	157937523
ENSE00001381139	157823246	157823446
ENSE00001434680	157867547	157867633
ENSE00003441706	157901898	157902045
ENSE00003444244	157896827	157896998

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.5569 / max 484.0993, expressed in 1808 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70785	36.1672	1808
70786	1.5441	962
70782	0.9987	718
70784	0.8468	571
70783	0.5978	368
70787	0.5908	338
70770	0.3431	123
70775	0.2255	36
70777	0.0897	20
70778	0.0746	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.88	gold quality
ileal mucosa	UBERON:0000331	96.50	gold quality
superficial temporal artery	UBERON:0001614	96.16	gold quality
calcaneal tendon	UBERON:0003701	95.68	gold quality
decidua	UBERON:0002450	95.66	gold quality
right coronary artery	UBERON:0001625	95.35	gold quality
tendon of biceps brachii	UBERON:0008188	95.21	gold quality
cauda epididymis	UBERON:0004360	95.17	gold quality
layer of synovial tissue	UBERON:0007616	95.06	gold quality
tibial artery	UBERON:0007610	95.02	gold quality
popliteal artery	UBERON:0002250	95.01	gold quality
synovial joint	UBERON:0002217	94.97	gold quality
tendon	UBERON:0000043	94.93	gold quality
stromal cell of endometrium	CL:0002255	94.87	gold quality
aorta	UBERON:0000947	94.81	gold quality
descending thoracic aorta	UBERON:0002345	94.74	gold quality
gall bladder	UBERON:0002110	94.66	gold quality
oral cavity	UBERON:0000167	94.65	gold quality
thoracic aorta	UBERON:0001515	94.57	gold quality
ascending aorta	UBERON:0001496	94.54	gold quality
placenta	UBERON:0001987	94.31	gold quality
corpus epididymis	UBERON:0004359	94.21	gold quality
secondary oocyte	CL:0000655	94.09	gold quality
smooth muscle tissue	UBERON:0001135	94.06	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.00	gold quality
endocervix	UBERON:0000458	93.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.85	gold quality
colonic mucosa	UBERON:0000317	93.76	gold quality
left coronary artery	UBERON:0001626	93.72	gold quality
upper arm skin	UBERON:0004263	93.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.55
E-CURD-88	yes	4.26
E-CURD-112	no	3.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

130 targeting SNX9, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
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-5692A	100.00	74.40	6850
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 30)

• The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation (PMID:11799118)
• SNX9 may function to assist AP-2 in its role at the plasma membrane. (PMID:11879186)
• SNX9 may be recruited together with dynamin-2 and become co-assembled with AP-2 and clathrin at the plasma membrane (PMID:12952949)
• SNX9-dependent recruitment of Dyn2 to the membrane is regulated by an interaction between SNX9 and aldolase (PMID:15299020)
• SNX9 is required for efficient clathrin-mediated endocytosis and suggest that it functions to regulate dynamin activity (PMID:15703209)
• Data show that in the presence of SNX9, synaptojanin-1 is able to colocalize with distinct ACK1 containing vesicles. (PMID:16137687)
• Dimerization, which is mediated by the BAR domain, is essential for the intracellular function of SH3PX1. (PMID:16316319)
• identified sorting nexin 9 (SNX9) as a host cell enteropathogenic E. coli EspF binding partner protein, which binds EspF via its amino-terminal SH3 region (PMID:16585770)
• the WASp/SNX9/p85/CD28 complex enables a unique interface of endocytic, actin polymerizing, and signal transduction pathways required for CD28-mediated T cell costimulation (PMID:17242350)
• SNX9 is directly involved in coupling actin dynamics to achieve membrane remodeling during multiple modes of endocytosis (PMID:17609109)
• SNX9 PX and BAR domains work in concert in targeting and tubulation of phosphoinositide-containing membranes. (PMID:17948057)
• crystallization and x-ray diffraction of SNX9 (PMID:18065239)
• SNX9 functions in the coordination of membrane remodeling and fission via interactions with actin-regulating proteins, endocytic proteins and PtdIns(4,5)P2-metabolizing enzymes (PMID:18388313)
• Tip-to-tip interactions between the BAR domains in a trigonal crystal form of Snx9(PX-BAR) reminiscent of functionally important interactions described for F-BAR domains. (PMID:18940612)
• Findings suggest that EspF promotes EPEC invasion of intestinal epithelial cells by harnessing the membrane-deforming activity of SNX9. (PMID:20088948)
• SNX9 binding to aldolase is structurally precluded by the binding of substrate to the active site. (PMID:20129922)
• The interaction with SNX9 is mediated by the proline-rich domain (PRD) of Itch, a domain distinct from the conventional WW recognition domain, and the SH3 domain of SNX9. (PMID:20491914)
• study identifies critical amino acids within the BAR domains of SNX9 and SNX33 as determinants for the specificity of BAR domain-mediated interactions and suggests that SNX9 and SNX33 have distinct molecular functions. (PMID:20964629)
• The sorting nexin 9 (SNX9) subfamily members - SNX9, SNX18 and SNX33 - are required for progression and completion of mitosis. (PMID:22718350)
• SNX9 and CHC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association. (PMID:23861900)
• this study shows that SNX9 uses a unique mechanism to induce the tubulation of the plasma membrane which mediates proper membrane deformation during clathrin-mediated endocytosis. (PMID:25256216)
• reduced levels of SNX9 were observed in blood samples from colorectal cancer patients, emphasizing the feasibility of its use as a diagnostic and prognostic biomarker sensing the host’s immune status and inflammatory stage. (PMID:26608909)
• The diversified changes associated with SNX9 expression in cancer highlight its importance as a central regulator of cancer cell behavior. (PMID:27278018)
• In conclusion, the authors identified SNX9 as a facilitator of podocin endocytosis in severe podocyte injury and demonstrated the expression of SNX9 in the podocytes of both nephropathy model mice and human patients with irreversible glomerular disease. (PMID:28266622)
• SNX9 assembles into ring-like structures around the endocytic vesicles (PMID:28627515)
• SNX9 knockdown revealed a nonredundant effect on overall ADAM9 protein levels, resulting in increased ADAM9 levels at the cell surface (PMID:29622675)
• SNX9 depletion significantly delayed the recycling of integrin beta1 (PMID:30784076)
• NECAP recruits drivers of late stages of clathrin-coated pit (CCP) formation, including SNX9, via a site distinct from where NECAP binds AP2. (PMID:31430451)
• SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling. (PMID:35050850)
• Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy. (PMID:36732507)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx9a	ENSDARG00000000837
danio_rerio	snx9b	ENSDARG00000069302
mus_musculus	Snx9	ENSMUSG00000002365
rattus_norvegicus	Snx9	ENSRNOG00000046874

Paralogs (15): SNX11 (ENSG00000002919), SNX1 (ENSG00000028528), SNX10 (ENSG00000086300), SNX5 (ENSG00000089006), SNX8 (ENSG00000106266), SNX3 (ENSG00000112335), SNX4 (ENSG00000114520), SNX6 (ENSG00000129515), SNX12 (ENSG00000147164), SNX30 (ENSG00000148158), SNX7 (ENSG00000162627), SNX32 (ENSG00000172803), SNX33 (ENSG00000173548), SNX18 (ENSG00000178996), SNX2 (ENSG00000205302)

Protein

Protein identifiers

Sorting nexin-9 — Q9Y5X1 (reviewed: Q9Y5X1)

Alternative names: SH3 and PX domain-containing protein 1, SH3 and PX domain-containing protein 3A

All UniProt accessions (14): Q9Y5X1, A0A087WVE4, A0A087WZW2, A0A7P0T8C7, A0A7P0T8D4, A0A7P0T8L2, A0A7P0T8M2, A0A7P0T8S8, A0A7P0T8Z2, A0A7P0T8Z7, A0A7P0TBD0, A0A7P0TBI9, A0A7P0Z4A2, A0A7P0Z4A5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate.

Subunit / interactions. Homodimer, and homooligomer. Heterodimer with SNX18. Interacts with ITCH. Interacts (via SH3 domain) with TNK2, WASL and ACTR3. Identified in a complex with TNK2 and clathrin heavy chains. Identified in a complex with the AP-2 complex, clathrin and DNM2. Interacts (via SH3 domain) with DNM1 and DNM2. Identified in an oligomeric complex containing DNM1 and SNX9. Interacts with FCHSD1. Interacts with ADAM9 and ADAM15 cytoplasmic tails.

Subcellular location. Cytoplasmic vesicle membrane. Cell membrane. Cytoplasmic vesicle. Clathrin-coated vesicle. Golgi apparatus. trans-Golgi network. Cell projection. Ruffle. Cytoplasm.

Tissue specificity. Widely expressed, with highest levels in heart and placenta, and lowest levels in thymus and peripheral blood leukocytes.

Post-translational modifications. Ubiquitinated by ITCH. Phosphorylated on tyrosine residues by TNK2. Phosphorylation promotes its activity in the degradation of EGFR.

Domain organisation. The PX domain mediates interaction with membranes enriched in phosphatidylinositol phosphate. Has high affinity for phosphatidylinositol 4,5-bisphosphate, but can also bind to membranes enriched in other phosphatidylinositol phosphates.

Similarity. Belongs to the sorting nexin family.

RefSeq proteins (1): NP_057308* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR001683	PX_dom	Domain
IPR014536	Snx9_fam	Family
IPR019497	Sorting_nexin_WASP-bd-dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR035558	SNX9_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037425	SNX9_BAR	Domain
IPR037426	SNX9_PX	Domain

Pfam: PF00787, PF07653, PF10456

UniProt features (63 total): helix 19, strand 13, modified residue 7, mutagenesis site 6, turn 4, compositionally biased region 4, domain 3, binding site 3, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3DYT	X-RAY DIFFRACTION	2.08
3LGE	X-RAY DIFFRACTION	2.2
2RAJ	X-RAY DIFFRACTION	2.45
2RAK	X-RAY DIFFRACTION	3
2RAI	X-RAY DIFFRACTION	3.2
3DYU	X-RAY DIFFRACTION	4.1
7OJ9	SOLUTION NMR
9R4W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5X1-F1	80.54	0.66

Functional residue map

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

Ligand- & substrate-binding residues (3): 286; 288; 327

Post-translational modifications (7): 116, 121, 197, 200, 216, 239, 288

Mutagenesis-validated functional residues (6):

Position	Phenotype
287	abolishes membrane tubulation activity. abolishes binding to phosphatidylinositol 3-phosphate, but not to phosphatidylin
313	abolishes binding to phosphatidylinositol 3-phosphate, but not to phosphatidylinositol 4,5-bisphosphate; when associated
363	strongly reduced membrane binding.
366–367	loss of membrane binding.
522	abolishes membrane tubulation activity; when associated with e-528.
528	abolishes membrane tubulation activity; when associated with e-522.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 362 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_MITOTIC_CYTOKINESIS, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_GTPASE_ACTIVITY, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE

GO Biological Process (18): mitotic cytokinesis (GO:0000281), intracellular protein transport (GO:0006886), endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), endosomal transport (GO:0016197), positive regulation of actin filament polymerization (GO:0030838), cleavage furrow formation (GO:0036089), positive regulation of GTPase activity (GO:0043547), positive regulation of protein kinase activity (GO:0045860), positive regulation of membrane protein ectodomain proteolysis (GO:0051044), lipid tube assembly (GO:0060988), protein-containing complex assembly (GO:0065003), plasma membrane tubulation (GO:0097320), regulation of synaptic vesicle endocytosis (GO:1900242), mitotic cell cycle (GO:0000278), positive regulation of catabolic process (GO:0009896), protein transport (GO:0015031), cell division (GO:0051301)

GO Molecular Function (9): 1-phosphatidylinositol binding (GO:0005545), ubiquitin protein ligase binding (GO:0031625), phosphatidylinositol binding (GO:0035091), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (15): ruffle (GO:0001726), cytoplasm (GO:0005737), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), clathrin-coated vesicle (GO:0030136), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cuticular plate (GO:0032437), extracellular exosome (GO:0070062), presynapse (GO:0098793), Golgi apparatus (GO:0005794), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Membrane Trafficking	2
trans-Golgi Network Vesicle Budding	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	3
cytoskeleton-dependent cytokinesis	2
intracellular protein localization	2
intracellular transport	2
vesicle-mediated transport	2
binding	2
membrane	2
endomembrane system	2
mitotic cell cycle	1
mitotic cell cycle process	1
protein transport	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
endocytosis	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cytokinetic process	1
plasma membrane invagination	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
membrane protein ectodomain proteolysis	1
positive regulation of protein catabolic process	1
positive regulation of proteolysis	1
regulation of membrane protein ectodomain proteolysis	1
protein-lipid complex assembly	1
cellular component assembly	1
protein-containing complex organization	1
plasma membrane organization	1
regulation of endocytosis	1
synaptic vesicle endocytosis	1

Protein interactions and networks

STRING

1214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX9	ADAM15	Q13444	977
SNX9	ADAM9	Q13443	967
SNX9	WASL	O00401	956
SNX9	WAS	P42768	898
SNX9	SH3GL2	Q99962	869
SNX9	BIN1	O00499	838
SNX9	AMPH	P49418	831
SNX9	SYNJ2	O15056	817
SNX9	SYNJ1	O43426	801
SNX9	FCHSD1	Q86WN1	728
SNX9	DNM1	Q05193	709
SNX9	ITSN1	Q15811	704
SNX9	EPN3	Q9H201	699
SNX9	EPN2	O95208	696
SNX9	ITSN2	Q9NZM3	692

IntAct

176 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
SNX9	DNM2	psi-mi:“MI:0915”(physical association)	0.920
DNM2	SNX9	psi-mi:“MI:0915”(physical association)	0.920
SNX9	DNM2	psi-mi:“MI:0403”(colocalization)	0.920
DNM2	SNX9	psi-mi:“MI:0407”(direct interaction)	0.920
DNM1	SNX9	psi-mi:“MI:0915”(physical association)	0.870
DNM1	SNX9	psi-mi:“MI:0407”(direct interaction)	0.870
SNX9	SYNJ1	psi-mi:“MI:0914”(association)	0.790
SNX9	SYNJ1	psi-mi:“MI:0407”(direct interaction)	0.790
SYNJ1	SNX9	psi-mi:“MI:0915”(physical association)	0.790
ADAM15	SNX9	psi-mi:“MI:0407”(direct interaction)	0.750
ADAM15	SNX9	psi-mi:“MI:0915”(physical association)	0.750
SNX9	ADAM15	psi-mi:“MI:0915”(physical association)	0.750
SNX9	SNX9	psi-mi:“MI:0407”(direct interaction)	0.740
SNX9	SNX9	psi-mi:“MI:0915”(physical association)	0.740
ANAPC16	BUB1B	psi-mi:“MI:0914”(association)	0.730

BioGRID (232): SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SNX9 (Two-hybrid), SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SNX9 (Proximity Label-MS), SNX9 (Proximity Label-MS), SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SNX9 (PCA), SNX9 (Affinity Capture-MS), SNX9 (Affinity Capture-MS)

ESM2 similar proteins: A0A098DRQ4, A1A4L0, A1CAN8, A1DF15, A1L1C7, A6RJQ7, A7E559, A7KAL4, B2AVN3, C8VDI2, C8VDQ4, I1RKA1, I1S4N7, O60749, O95219, P0C220, P83094, Q0WQF4, Q2TBW7, Q2U7R4, Q2UB56, Q4IR87, Q4WCV3, Q4WUE5, Q4WZF1, Q524W4, Q5AZC9, Q5R4C2, Q5R6M6, Q5R9A9, Q6NRZ4, Q6P3Q6, Q6PCS4, Q6VVX2, Q7SB54, Q7SB97, Q8J2R3, Q8K3H0, Q8VWF1, Q91VH2

Diamond homologs: A0A1B7YDZ4, I1RXT2, O14243, O60107, O60493, O70492, O70493, P0CR58, P0CR59, P0CR60, P0CR61, P0CR62, P0CR63, P40959, P47057, Q08826, Q08DD7, Q1RMH8, Q2U4K2, Q2UB56, Q3MPQ4, Q4I1H6, Q4P1V3, Q4PHC3, Q4WQI6, Q4WWS3, Q4WZF1, Q522W5, Q5A748, Q5B797, Q5H7C3, Q5R5V1, Q5U211, Q6C2S9, Q6CTQ0, Q6CUC4, Q6FNH2, Q6FPT9, Q6FT03, Q75C43

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SNX9	down-regulates	EGFR
SNX9	up-regulates	DNM1	binding
SNX9	up-regulates	DNM2	binding
TNK2	up-regulates	SNX9	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
Signaling by EGFR	5	15.5×	4e-03
Clathrin-mediated endocytosis	13	10.6×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of epidermal growth factor receptor signaling pathway	5	19.2×	2e-03
epidermal growth factor receptor signaling pathway	7	13.4×	5e-04
positive regulation of autophagy	6	9.7×	7e-03
endocytosis	12	8.9×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3906 predictions. Top by Δscore:

Variant	Effect	Δscore
6:157867536:A:AG	acceptor_gain	1.0000
6:157867537:C:G	acceptor_gain	1.0000
6:157867541:TGATA:T	acceptor_loss	1.0000
6:157867542:GATA:G	acceptor_loss	1.0000
6:157867544:TAG:T	acceptor_loss	1.0000
6:157867545:A:AG	acceptor_gain	1.0000
6:157867545:A:C	acceptor_loss	1.0000
6:157867546:G:A	acceptor_loss	1.0000
6:157867546:G:GG	acceptor_gain	1.0000
6:157867546:GGCTC:G	acceptor_gain	1.0000
6:157867631:CCGG:C	donor_loss	1.0000
6:157867632:CGGT:C	donor_loss	1.0000
6:157867634:G:GG	donor_gain	1.0000
6:157867634:G:T	donor_loss	1.0000
6:157867635:T:C	donor_loss	1.0000
6:157873177:G:GG	donor_gain	1.0000
6:157875173:CCAGG:C	donor_loss	1.0000
6:157875175:AGG:A	donor_loss	1.0000
6:157875178:T:G	donor_loss	1.0000
6:157901869:AACT:A	acceptor_gain	1.0000
6:157901890:A:AG	acceptor_gain	1.0000
6:157901891:C:G	acceptor_gain	1.0000
6:157901896:A:AG	acceptor_gain	1.0000
6:157901896:AGC:A	acceptor_loss	1.0000
6:157901897:G:GA	acceptor_gain	1.0000
6:157901897:GC:G	acceptor_gain	1.0000
6:157901897:GCA:G	acceptor_gain	1.0000
6:157901897:GCAA:G	acceptor_gain	1.0000
6:157901897:GCAAC:G	acceptor_gain	1.0000
6:157902042:ACAA:A	donor_gain	1.0000

AlphaMissense

3951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:157873117:T:A	W39R	1.000
6:157873117:T:C	W39R	1.000
6:157873157:T:A	V52D	1.000
6:157909686:T:A	W243R	1.000
6:157909686:T:C	W243R	1.000
6:157909688:G:C	W243C	1.000
6:157909688:G:T	W243C	1.000
6:157909758:A:G	K267E	1.000
6:157909760:G:C	K267N	1.000
6:157909760:G:T	K267N	1.000
6:157909768:T:A	I270N	1.000
6:157909773:T:C	Y272H	1.000
6:157909773:T:G	Y272D	1.000
6:157909933:G:C	R286T	1.000
6:157909933:G:T	R286M	1.000
6:157909934:G:C	R286S	1.000
6:157909934:G:T	R286S	1.000
6:157909935:T:C	Y287H	1.000
6:157909935:T:G	Y287D	1.000
6:157909936:A:G	Y287C	1.000
6:157909938:A:G	K288E	1.000
6:157909940:G:C	K288N	1.000
6:157909940:G:T	K288N	1.000
6:157909944:T:C	F290L	1.000
6:157909946:T:A	F290L	1.000
6:157909946:T:G	F290L	1.000
6:157909950:T:A	W292R	1.000
6:157909950:T:C	W292R	1.000
6:157909952:G:C	W292C	1.000
6:157909952:G:T	W292C	1.000

dbSNP variants (sampled 300 via entrez): RS1000025358 (6:157897408 C>G,T), RS1000031442 (6:157883614 C>T), RS1000057150 (6:157840011 A>G), RS1000075149 (6:157868027 C>T), RS1000144916 (6:157902814 T>C), RS1000155031 (6:157914491 T>C), RS1000159494 (6:157924668 A>G), RS1000225708 (6:157919372 A>G), RS1000278178 (6:157919095 T>C), RS1000285653 (6:157878494 A>G), RS1000286136 (6:157890675 C>T), RS1000293591 (6:157905763 C>A,G), RS1000313091 (6:157917901 A>G), RS1000329886 (6:157925835 T>C), RS1000344349 (6:157867308 G>C)

Disease associations

OMIM: gene MIM:605952 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002746_6	Lipoprotein (a) - cholesterol levels	5.000000e-17
GCST004616_184	Platelet distribution width	4.000000e-11
GCST004641_20	Borderline personality disorder	4.000000e-06
GCST005519_2	Heart rate response to beta blockers	1.000000e-08
GCST009391_179	Metabolite levels	7.000000e-06
GCST012488_32	L1-L4 bone mineral density x serum urate levels interaction	2.000000e-07
GCST90002401_542	Platelet distribution width	4.000000e-19
GCST90002401_543	Platelet distribution width	4.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0007984	platelet component distribution width
EFO:0007766	response to beta blocker
EFO:0010476	dimethylglycine measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066410 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2364349	SNX9		0.00	0

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
6.31	Kd	494	nM	CHEMBL3752910
6.31	ED50	494	nM	CHEMBL3752910

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149942: Binding affinity to human SNX9 incubated for 45 mins by Kinobead based pull down assay	kd	0.4940	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation, affects cotreatment, affects expression, increases abundance	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Benzo(a)pyrene	affects methylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
ginger extract	increases abundance, affects cotreatment, affects expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
incobotulinumtoxinA	increases expression	1
bisphenol AF	increases expression	1
Vorinostat	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzoates	increases expression	1
Caffeine	increases phosphorylation	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
CHEMBL5652984	Binding	Binding affinity to human SNX9 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

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TP91	HAP1 SNX9 (-) 1	Cancer cell line	Male
CVCL_TP92	HAP1 SNX9 (-) 2	Cancer cell line	Male
CVCL_TP93	HAP1 SNX9 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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