SNX3

Summary

SNX3 (sorting nexin 3, HGNC:11174) is a protein-coding gene on chromosome 6q21, encoding Sorting nexin-3 (O60493). Phosphoinositide-binding protein required for multivesicular body formation.

This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like most family members. This protein interacts with phosphatidylinositol-3-phosphate, and is involved in protein trafficking. A pseudogene of this gene is present on the sex chromosomes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 8724 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MMEP syndrome (Limited, GenCC)
• Clinical variants (ClinVar): 18 total
• Druggable target: yes
• MANE Select transcript: NM_003795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11174
Approved symbol	SNX3
Name	sorting nexin 3
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	Grd19
Ensembl gene	ENSG00000112335
Ensembl biotype	protein_coding
OMIM	605930
Entrez	8724

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000230085, ENST00000349379, ENST00000368979, ENST00000426155, ENST00000909211, ENST00000909212, ENST00000909213, ENST00000909214, ENST00000946326, ENST00000946327

RefSeq mRNA: 4 — MANE Select: NM_003795 NM_001300928, NM_001300929, NM_003795, NM_152827

CCDS: CCDS5064, CCDS5065, CCDS75501

Canonical transcript exons

ENST00000230085 — 4 exons

Exon	Start	End
ENSE00000761694	108222950	108223045
ENSE00001345247	108260760	108261040
ENSE00001887973	108211222	108212254
ENSE00003623823	108214498	108214622

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 182.4463 / max 2144.4168, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74958	182.4463	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.58	gold quality
visceral pleura	UBERON:0002401	99.53	gold quality
middle temporal gyrus	UBERON:0002771	99.53	gold quality
parietal pleura	UBERON:0002400	99.52	gold quality
endothelial cell	CL:0000115	99.50	gold quality
pleura	UBERON:0000977	99.50	gold quality
heart right ventricle	UBERON:0002080	99.46	gold quality
germinal epithelium of ovary	UBERON:0001304	99.38	gold quality
parotid gland	UBERON:0001831	99.32	gold quality
choroid plexus epithelium	UBERON:0003911	99.29	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.28	gold quality
skin of hip	UBERON:0001554	99.26	gold quality
entorhinal cortex	UBERON:0002728	99.24	gold quality
deltoid	UBERON:0001476	99.21	gold quality
superior frontal gyrus	UBERON:0002661	99.20	gold quality
esophagus squamous epithelium	UBERON:0006920	99.18	gold quality
postcentral gyrus	UBERON:0002581	99.15	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.15	gold quality
gingival epithelium	UBERON:0001949	99.13	gold quality
orbitofrontal cortex	UBERON:0004167	99.13	gold quality
epithelium of esophagus	UBERON:0001976	99.12	gold quality
adult organism	UBERON:0007023	99.12	gold quality
pancreatic ductal cell	CL:0002079	99.10	gold quality
oral cavity	UBERON:0000167	99.10	gold quality
frontal pole	UBERON:0002795	99.10	gold quality
right adrenal gland	UBERON:0001233	99.09	gold quality
right adrenal gland cortex	UBERON:0035827	99.09	gold quality
biceps brachii	UBERON:0001507	99.08	gold quality
myocardium	UBERON:0002349	99.08	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	4121.54
E-MTAB-10553	yes	2777.08
E-CURD-88	yes	1956.57
E-MTAB-10042	yes	1912.59
E-GEOD-149689	yes	1829.44
E-MTAB-8271	yes	1403.34
E-MTAB-8205	yes	627.51
E-MTAB-6701	yes	49.72
E-HCAD-4	yes	47.74
E-HCAD-5	yes	33.81
E-CURD-46	yes	31.74
E-HCAD-1	yes	30.80
E-MTAB-9467	yes	22.87
E-HCAD-13	yes	20.90
E-HCAD-6	yes	18.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting SNX3, 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-340-5P	100.00	72.50	4437
HSA-MIR-432-3P	100.00	67.86	705
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-6758-5P	100.00	66.21	1470
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 15)

• Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation t(6;13)(q21;q12) and microcephaly, microphthalmia, ectrodactyly, prognathism (MMEP) phenotype (PMID:12471201)
• we cannot exclude the possibility that deletions at SNX3 may underlie MMEP, given that sequencing is unable to distinguish between homozygosity across loci versus large deletions (PMID:17655765)
• Data show that Hrs is essential for lysosomal targeting but not multivesicular body biogenesis and transport to late endosomes, while SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. (PMID:18767904)
• SNX3 plays a significant role in regulating the maturation of Salmonella containing vacuoles. (PMID:20482551)
• SNX3 and SNX5 play essential roles in the aspirin-mediated accumulation of endocytosed-TfnR at the early/sorting endosome (PMID:22159558)
• This study found that four significant SNX3 SNPs in the discovery sample were replicated in a community-based sample of Israeli-Arabs (PMID:22673115)
• SNX3 negatively regulates phagocytosis in DC possibly by modulating recruitment of essential PI3P lipid-binding proteins of the phagocytic pathways, such as EEA1, to phagosomal membranes. (PMID:23237080)
• Data show that over-expression of sorting nexin 3 (hSNX3) alters the morphology of colon cancer SW620 cells, but hardly affects cell migration. (PMID:26271979)
• X-ray crystallographic analysis of a 4-component complex comprising the VPS26 & VPS35 subunits of retromer, sorting nexin SNX3, & recycling signal from the divalent cation transporter DMT1-II; analysis identifies a binding site for canonical recycling signals at the interface between VPS26 & SNX3; shows cooperative interactions among the VPS subunits, SNX3 & cargo that couple signal-recognition to membrane recruitment. (PMID:27889239)
• SNX3-retromer complex regulates the surface expression and function of PC1 and PC2 (PMID:28620080)
• SNX3 regulates amyloid beta production by influencing the internalization of amyloid precursor protein in HEK293T cells and may have a role in the pathogenesis of Alzheimer’s disease. (PMID:29414832)
• an evolutionary conserved MON2:DOPEY2:ATP9A complex is required for SNX3 retromer mediation of Wntless sorting and Wnt secretion (PMID:30213940)
• sorting nexin SNX3 is transported with Rab5a vesicles and that its PX domain enables vesicle-phagosome contact by binding to PI(3)P in the phagosomal coat. Moreover, the C-terminal region of SNX3 recruits galectin-9, a lectin implicated in protein and membrane recycling, which we identify as a further regulator of phagosome compaction. (PMID:31337623)
• LINC01614 promotes osteosarcoma progression via miR-520a-3p/SNX3 axis. (PMID:33753211)
• Sorting nexin 3 induces heart failure via promoting retromer-dependent nuclear trafficking of STAT3. (PMID:33947971)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx3	ENSDARG00000008678
mus_musculus	Snx3	ENSMUSG00000019804
rattus_norvegicus	Snx3	ENSRNOG00000046705
drosophila_melanogaster	Snx3	FBGN0038065
caenorhabditis_elegans	snx-3	WBGENE00006503

Paralogs (15): SNX11 (ENSG00000002919), SNX1 (ENSG00000028528), SNX10 (ENSG00000086300), SNX5 (ENSG00000089006), SNX8 (ENSG00000106266), SNX4 (ENSG00000114520), SNX6 (ENSG00000129515), SNX9 (ENSG00000130340), SNX12 (ENSG00000147164), SNX30 (ENSG00000148158), SNX7 (ENSG00000162627), SNX32 (ENSG00000172803), SNX33 (ENSG00000173548), SNX18 (ENSG00000178996), SNX2 (ENSG00000205302)

Protein

Protein identifiers

Sorting nexin-3 — O60493 (reviewed: O60493)

Alternative names: Protein SDP3

All UniProt accessions (1): O60493

UniProt curated annotations — full annotation on UniProt →

Function. Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Can also bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2). Plays a role in protein transport between cellular compartments. Together with RAB7A facilitates endosome membrane association of the retromer cargo-selective subcomplex (CSC/VPS). May in part act as component of the SNX3-retromer complex which mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G. Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes. Involved in iron homeostasis through regulation of endocytic recycling of the transferrin receptor TFRC presumably by delivering the transferrin:transferrin receptor complex to recycling endosomes; the function may involve the CSC retromer subcomplex. Involved in regulation of neurite outgrowth in primary neurons. Required for trafficking of WLS to the early endosome for recycling which promotes both canonical and non-canonical WNT signaling and is essential for neural tube closure. (Microbial infection) In the case of Salmonella enterica infection, plays a role in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs.

Subunit / interactions. Interacts with VPS26A, VPS29 and VPS35; the interaction with VPS35 is direct. The association with the retromer CSC subcomplex subunits is proposed to represent a functional distinct retromer variant described as SNX3-retromer complex. Interacts with USP10 and SCNN1A. Interacts with TRFC. Interacts with SNX8; 2 molecules of SNX8 seems to associate with one molecule of SNX3. Interacts with PTPRU. Interacts with MON2 and DOP1B.

Subcellular location. Early endosome. Cytoplasmic vesicle. Phagosome.

Post-translational modifications. Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP10.

Disease relevance. A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).

Domain organisation. The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)).

Similarity. Belongs to the sorting nexin family.

Isoforms (4)

UniProt ID	Names	Canonical?
O60493-1	1	yes
O60493-2	2, SNX 3A
O60493-3	3
O60493-4	4

RefSeq proteins (4): NP_001287857, NP_001287858, NP_003786, NP_690040 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR042137	PX_SNX3_Vert	Domain
IPR051074	Sorting_Nexin	Family

Pfam: PF00787

UniProt features (47 total): mutagenesis site 16, helix 8, strand 5, binding site 4, modified residue 3, splice variant 3, sequence conflict 2, initiator methionine 1, chain 1, cross-link 1, sequence variant 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2YPS	X-RAY DIFFRACTION	2.6
5F0J	X-RAY DIFFRACTION	2.7
5F0P	X-RAY DIFFRACTION	2.78
5F0M	X-RAY DIFFRACTION	3.1
5F0L	X-RAY DIFFRACTION	3.2
7BLO	ELECTRON MICROSCOPY	9.5
2MXC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60493-F1	89.15	0.65

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 (4): 70; 72; 95; 118

Post-translational modifications (4): 72, 95, 2, 43

Mutagenesis-validated functional residues (16):

Position	Phenotype
9–10	loss of vps35 binding.
22–28	loss of vps35 binding.
22	loss of vps35 binding.
28	abolishes interaction with retromer cargo-selective subcomplex vps26a:vps29:vps35; when associated with a-30 and a-32.
30–32	loss of vps35 binding.
30	abolishes interaction with retromer cargo-selective subcomplex vps26a:vps29:vps35; when associated with a-28 and a-32.
32	abolishes interaction with retromer cargo-selective subcomplex vps26a:vps29:vps35; when associated with a-28 and a-30.
50	loss of vps35 binding.
69–71	abolishes binding to phosphatidylinositol 3-phosphate.
71	abolishes binding to phosphatidylinositol 3-phosphate.
75	increases vps35 binding.
84–86	decreases vps35 binding.
99–110	increases vps35 binding.
154	decreases vps35 binding.
156	decreases vps35 binding.
160	loss of vps35 binding.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-5689880	Ub-specific processing proteases
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 261 (showing top): GOBP_ENDOSOME_ORGANIZATION, GOBP_VESICLE_ORGANIZATION, YANG_BREAST_CANCER_ESR1_LASER_DN, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MEMBRANE_DOCKING, GOLDRATH_ANTIGEN_RESPONSE, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (14): response to bacterium (GO:0009617), membrane invagination (GO:0010324), positive regulation of neuron projection development (GO:0010976), protein transport (GO:0015031), protein to membrane docking (GO:0022615), regulation of Wnt signaling pathway (GO:0030111), endocytic recycling (GO:0032456), late endosome to Golgi transport (GO:0034499), negative regulation of protein catabolic process (GO:0042177), host-mediated suppression of symbiont invasion (GO:0046597), negative regulation of phagocytosis (GO:0050765), negative regulation of protein transport (GO:0051224), intralumenal vesicle formation (GO:0070676), negative regulation of early endosome to late endosome transport (GO:2000642)

GO Molecular Function (10): phosphatidylinositol-5-phosphate binding (GO:0010314), protein phosphatase binding (GO:0019903), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol-4-phosphate binding (GO:0070273), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), retromer complex binding (GO:1905394), protein binding (GO:0005515), lipid binding (GO:0008289), phosphatidylinositol binding (GO:0035091), phosphatidylinositol phosphate binding (GO:1901981)

GO Cellular Component (12): cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), endosome membrane (GO:0010008), clathrin-coated vesicle (GO:0030136), retromer complex (GO:0030904), early endosome membrane (GO:0031901), early phagosome (GO:0032009), extracellular exosome (GO:0070062), endosome (GO:0005768), cytoplasmic vesicle (GO:0031410), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by WNT	1
Deubiquitination	1
Signal Transduction	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol phosphate binding	4
cytoplasm	3
anion binding	3
endosome membrane	2
binding	2
cellular anatomical structure	2
endosome	2
endomembrane system	2
response to other organism	1
membrane organization	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
membrane docking	1
regulation of signal transduction	1
Wnt signaling pathway	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
innate immune response	1
host-mediated perturbation of symbiont process	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1
protein transport	1
negative regulation of transport	1
regulation of protein transport	1
negative regulation of protein localization	1
negative regulation of establishment of protein localization	1
vesicle budding from membrane	1
endosome organization	1
negative regulation of intracellular transport	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX3	VPS35	Q96QK1	994
SNX3	VPS26A	O75436	982
SNX3	VPS29	Q9UBQ0	970
SNX3	SNX6	Q9UNH7	959
SNX3	SNX27	Q96L92	908
SNX3	SNX5	Q9Y5X3	894
SNX3	SERPINE2	P07093	833
SNX3	SNX8	Q9Y5X2	794
SNX3	VPS26B	Q4G0F5	788
SNX3	TBC1D5	Q92609	765
SNX3	SNX17	Q15036	758
SNX3	IFT122	Q9HBG6	700
SNX3	RAB7A	P51149	695
SNX3	SNX4	O95219	694
SNX3	SNX1	Q13596	649

IntAct

140 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
EGFR	SNX3	psi-mi:“MI:0915”(physical association)	0.580
SNX3	EGFR	psi-mi:“MI:2364”(proximity)	0.580
ARL6IP1	SNX3	psi-mi:“MI:0915”(physical association)	0.560
SNX3	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
SNX3	RPRM	psi-mi:“MI:0915”(physical association)	0.560
	SNX3	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
HSD17B6	NME2P1	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
SCNM1	SNX3	psi-mi:“MI:0914”(association)	0.530
SNX3	VPS26A	psi-mi:“MI:0914”(association)	0.530

BioGRID (257): ARL6IP1 (Two-hybrid), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Affinity Capture-MS), SNX3 (Reconstituted Complex), SNX3 (Reconstituted Complex), AKR1A1 (Co-fractionation), LOC101930400 (Co-fractionation), AKR1C2 (Co-fractionation)

ESM2 similar proteins: D3ZRP6, D4A055, F1QH17, O22715, O60493, O70492, O70493, O95619, P0CR61, P48454, P48455, Q0G819, Q15691, Q1RMH8, Q1RMS5, Q27889, Q28E02, Q2U4K2, Q3SYW1, Q3ZBD9, Q4I1H6, Q4WWS3, Q5R5V1, Q5R752, Q5R7Z5, Q5U211, Q5XH73, Q5ZKU1, Q5ZLC7, Q60EW9, Q61166, Q66HR2, Q66T82, Q68FK8, Q6AXU9, Q6C2S9, Q6IR85, Q6P848, Q6V291, Q76EZ2

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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 FLT3 ITD and TKD mutants	6	46.1×	3e-07
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	8	42.0×	2e-09
Downstream signal transduction	10	38.5×	3e-11
GRB2 events in EGFR signaling	5	38.5×	9e-06
SHC1 events in EGFR signaling	5	36.0×	1e-05
Constitutive Signaling by EGFRvIII	5	36.0×	1e-05
Signaling by FLT3 fusion proteins	6	34.6×	1e-06
Signaling by ERBB2 ECD mutants	5	33.9×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
retrograde transport, endosome to Golgi	7	10.2×	7e-03

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	8
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

784 predictions. Top by Δscore:

Variant	Effect	Δscore
6:108212253:CC:C	acceptor_gain	1.0000
6:108212254:CC:C	acceptor_gain	1.0000
6:108214491:CACT:C	donor_loss	1.0000
6:108214492:ACTT:A	donor_loss	1.0000
6:108214493:CT:C	donor_loss	1.0000
6:108214494:TT:T	donor_loss	1.0000
6:108214495:TA:T	donor_loss	1.0000
6:108214496:A:AC	donor_gain	1.0000
6:108214496:ACTTG:A	donor_loss	1.0000
6:108214497:C:CC	donor_gain	1.0000
6:108214497:CT:C	donor_gain	1.0000
6:108214497:CTT:C	donor_gain	1.0000
6:108214497:CTTG:C	donor_gain	1.0000
6:108222944:TCTTA:T	donor_loss	1.0000
6:108222945:CTTA:C	donor_loss	1.0000
6:108222946:TTA:T	donor_loss	1.0000
6:108222947:TA:T	donor_loss	1.0000
6:108222948:A:AC	donor_gain	1.0000
6:108222949:C:CC	donor_gain	1.0000
6:108222949:C:G	donor_loss	1.0000
6:108222949:CCTTG:C	donor_gain	1.0000
6:108223041:TTTGT:T	acceptor_gain	1.0000
6:108223042:TTGT:T	acceptor_gain	1.0000
6:108223046:C:CC	acceptor_gain	1.0000
6:108242061:A:C	donor_gain	1.0000
6:108212255:C:CC	acceptor_gain	0.9900
6:108212255:C:CG	acceptor_loss	0.9900
6:108212256:T:A	acceptor_loss	0.9900
6:108214497:CTTGT:C	donor_gain	0.9900
6:108214531:T:A	donor_gain	0.9900

AlphaMissense

1070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:108212242:A:C	H132Q	1.000
6:108212242:A:T	H132Q	1.000
6:108212243:T:C	H132R	1.000
6:108214516:A:G	L122P	1.000
6:108214527:T:A	R118S	1.000
6:108214527:T:G	R118S	1.000
6:108214615:A:T	V89D	1.000
6:108222999:C:A	R70I	1.000
6:108223001:T:A	R69S	1.000
6:108223001:T:G	R69S	1.000
6:108223002:C:G	R69T	1.000
6:108212204:A:G	L145S	0.999
6:108212206:A:C	F144L	0.999
6:108212206:A:T	F144L	0.999
6:108212207:A:G	F144S	0.999
6:108212208:A:G	F144L	0.999
6:108212216:A:G	L141P	0.999
6:108212237:A:G	L134P	0.999
6:108212244:G:C	H132D	0.999
6:108212246:C:T	G131D	0.999
6:108212249:G:T	A130D	0.999
6:108212250:C:G	A130P	0.999
6:108214506:A:C	F125L	0.999
6:108214506:A:T	F125L	0.999
6:108214507:A:G	F125S	0.999
6:108214508:A:G	F125L	0.999
6:108214516:A:T	L122Q	0.999
6:108214528:C:A	R118I	0.999
6:108214528:C:G	R118T	0.999
6:108214551:A:C	F110L	0.999

dbSNP variants (sampled 300 via entrez): RS1000034486 (6:108229665 C>A), RS1000083241 (6:108218419 T>C,G), RS1000099889 (6:108224247 G>C), RS1000111234 (6:108212494 T>A,C), RS1000134691 (6:108246306 G>A,C,T), RS1000157333 (6:108258530 G>A), RS1000230637 (6:108235384 T>A,G), RS1000261997 (6:108235624 G>A,T), RS1000313335 (6:108252312 G>C,T), RS1000314134 (6:108246468 G>C), RS1000441897 (6:108258305 A>G), RS1000465760 (6:108240661 G>C), RS1000492133 (6:108257261 GTAAT>G), RS1000527452 (6:108214049 C>A,G,T), RS1000533670 (6:108251898 C>A)

Disease associations

OMIM: gene MIM:605930 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
MMEP syndrome	Limited	Autosomal dominant

Mondo (1): MMEP syndrome (MONDO:0011045)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537686	Microcephaly, microphthalmia, ectrodactyly of lower limbs, and prognathism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465275 (SINGLE PROTEIN)

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

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
7.35	Kd	44.84	nM	CHEMBL5653589
7.35	ED50	44.84	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149463: Binding affinity to human SNX3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0448	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases expression, increases activity	1
bisphenol AF	increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Cisplatin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Furaldehyde	affects localization, decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338459	Binding	Binding affinity to Snx3 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3HV	Abcam HEK293T SNX3 KO	Transformed cell line	Female
CVCL_TP89	HAP1 SNX3 (-) 1	Cancer cell line	Male
CVCL_TP90	HAP1 SNX3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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