SNX1

Summary

SNX1 (sorting nexin 1, HGNC:11172) is a protein-coding gene on chromosome 15q22.31, encoding Sorting nexin-1 (Q13596). Involved in several stages of intracellular trafficking.

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 endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosomes. This protein may form oligomeric complexes with family members. This gene results in three transcript variants encoding distinct isoforms.

Source: NCBI Gene 6642 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total
• Druggable target: yes
• MANE Select transcript: NM_003099

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11172
Approved symbol	SNX1
Name	sorting nexin 1
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	SNX1A, MGC8664, HsT17379, Vps5
Ensembl gene	ENSG00000028528
Ensembl biotype	protein_coding
OMIM	601272
Entrez	6642

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261889, ENST00000380285, ENST00000558040, ENST00000559061, ENST00000559339, ENST00000559389, ENST00000559401, ENST00000559844, ENST00000559961, ENST00000560260, ENST00000560829, ENST00000560861, ENST00000561026, ENST00000625244, ENST00000909216, ENST00000909217, ENST00000909218, ENST00000909219, ENST00000909220, ENST00000955626, ENST00000955627

RefSeq mRNA: 3 — MANE Select: NM_003099 NM_001242933, NM_003099, NM_148955

CCDS: CCDS32266, CCDS32268, CCDS58371

Canonical transcript exons

ENST00000559844 — 15 exons

Exon	Start	End
ENSE00002557315	64095982	64096172
ENSE00003505339	64129916	64130029
ENSE00003526558	64131687	64131892
ENSE00003530891	64134664	64134807
ENSE00003540588	64126079	64126220
ENSE00003559630	64136330	64136410
ENSE00003592432	64127731	64127806
ENSE00003622581	64130228	64130321
ENSE00003642294	64127174	64127252
ENSE00003649498	64118117	64118244
ENSE00003658262	64123503	64123546
ENSE00003669418	64112573	64112684
ENSE00003677097	64136861	64136932
ENSE00003689569	64118788	64118854
ENSE00003849706	64137568	64144231

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.3452 / max 420.2201, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147162	66.7367	1827
147161	1.2521	569
147160	0.2225	80
147166	0.0821	25
147164	0.0424	11
147165	0.0094	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.10	gold quality
left lobe of thyroid gland	UBERON:0001120	98.91	gold quality
thyroid gland	UBERON:0002046	98.58	gold quality
right adrenal gland	UBERON:0001233	97.87	gold quality
right adrenal gland cortex	UBERON:0035827	97.72	gold quality
left adrenal gland	UBERON:0001234	97.61	gold quality
monocyte	CL:0000576	97.58	gold quality
upper lobe of left lung	UBERON:0008952	97.52	gold quality
ectocervix	UBERON:0012249	97.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.45	gold quality
mononuclear cell	CL:0000842	97.41	gold quality
leukocyte	CL:0000738	97.40	gold quality
left adrenal gland cortex	UBERON:0035825	97.40	gold quality
granulocyte	CL:0000094	97.36	gold quality
body of uterus	UBERON:0009853	97.14	gold quality
upper lobe of lung	UBERON:0008948	97.12	gold quality
smooth muscle tissue	UBERON:0001135	97.08	gold quality
rectum	UBERON:0001052	97.07	gold quality
body of stomach	UBERON:0001161	97.03	gold quality
adrenal cortex	UBERON:0001235	97.00	gold quality
adrenal gland	UBERON:0002369	96.98	gold quality
endocervix	UBERON:0000458	96.95	gold quality
right lung	UBERON:0002167	96.87	gold quality
spinal cord	UBERON:0002240	96.87	gold quality
minor salivary gland	UBERON:0001830	96.86	gold quality
adipose tissue	UBERON:0001013	96.85	gold quality
gall bladder	UBERON:0002110	96.84	gold quality
right lobe of liver	UBERON:0001114	96.77	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

191 targeting SNX1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-340-5P	100.00	72.50	4437
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-520G-5P	99.99	66.76	658
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 26)

• controls down-regulation of protease-activated receptor-1 (PMID:12058063)
• PX domain-dependent/early endosomal association of SNX1 is important for its ability to regulate the targeting of internalized epidermal growth factor receptor for lysosomal degradation (PMID:12198132)
• identified sorting nexin 1 (SNX1) as a novel partner of enterothelin-1 (ENT-1); show that Ent-1 and SNX1 co-eluted in macromolecular complexes containing part of epidermal growth factor receptor(EGFR) (PMID:12657642)
• SNX1 associates with a microdomain of the early endosome where it regulates tubular-based endosome-to-trans Golgi network retrieval of the cation-independent mannose-6-phosphate receptor. (PMID:15498486)
• NMR structure of the PX domain of SNX1 reveals an overall fold that is similar to high-affinity PX domains (PMID:15673616)
• HkRP1 is involved in the process of tubulation of sorting nexin-1 positive membranes from early endosome subdomains (PMID:15882442)
• These findings establish an essential role for endogenous SNX1 in sorting activated PAR1 to a distinct lysosomal degradative pathway that is independent of retromer, Hrs, and Tsg101. (PMID:16407403)
• Overexpression of SNX1 is able to attenuate the effect of SNX5 on epidermal growth factor (EGF) receptor degradation. (PMID:16487940)
• These observations indicate that the mammalian retromer complex assembles by sequential association of SNX1/2 and Vps26-Vps29-Vps35 subcomplexes on endosomal membranes and that SNX1 and SNX2 play interchangeable but essential roles. (PMID:17101778)
• The loss of SNX1 may play a significant role in the development and aggressiveness of human colon cancer, at least partially through the mechanism of increased signaling from endosomes. (PMID:17145813)
• Together, these findings demonstrate a role for SNX1 in retrieval of E-cadherin from a degradative endosomal pathway and in membrane trafficking pathways that regulate E-cadherin recycling. (PMID:17502486)
• sortilin and mannose-6-phosphate receptors recycle to the TGN in SNX1-dependent carriers, which we named endosome-to-TGN transport carriers (PMID:18088323)
• These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of G-protein coupled receptors. (PMID:20070609)
• SNX1 and SNX2 interact with Kalirin-7. Overexpression of SNX1 or SNX2 and Kalirin-7 partially redistributes both SNXs to the plasma membrane, and results in RhoG-dependent lamellipodia formation. (PMID:20604901)
• Results demonstrate that miR-95 increases proliferation by directly targeting SNX1, defining miR-95 as a new oncogenic miRNA in CRC. (PMID:21427358)
• SNX4, but not SNX1 and SNX8, is associated with the Rab11-recycling endosomes and that a high frequency of SNX4-mediated tubule formation is observed as endosomes undergo Rab4-to-Rab11 transition. (PMID:21973056)
• This study found that significant evidence of association with SNX1 (VEGAS p = 0.035) in patient with Alzheimer disease. (PMID:22673115)
• we suggest that SNX1 is involved in the negative regulation of ligand-induced EGFR phosphorylation and mediates EGFR/pEGFR trafficking out of early endosomes (PMID:22859339)
• SNX1 has a crucial role in D(5)R trafficking and SNX1 depletion results in D(5)R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension (PMID:23152498)
• miR-95 functions as an oncogene role in non-small cell lung cancer cells by directly targeting SNX1. (PMID:24835695)
• Results show that suppression of EGFR membrane recycling by SNX1 appears to be critical for the activation of EGFR /PI3K/AKT signaling pathway in human lung cancer cells. (PMID:25653196)
• SNX1 was down-regulated in CRC and associated with poor prognosis. Our data also showed that SNX1 inhibited the proliferation of CRC cells and increased the sensitivity to the most commonly used drugs for CRC. (PMID:26643894)
• Data suggest that GLP1R signaling in pancreatic beta-cells leading to insulin secretion involves interactions of GLP1R with HIP1, SNX1, and SNX27; HIP1 appears to regulate coupling of cell surface GLP1R activation with endocytosis; SNX1 and SNX27 appear to control balance between GLP1R plasma membrane recycling and lysosomal degradation. (PMID:29284659)
• Sorting nexin 1 loss results in increased oxidative stress and hypertension. (PMID:32293069)
• Biochemical basis for an interaction between SNX27 and the flexible SNX1 N-terminus. (PMID:34866035)
• Spatiotemporal regulation of the hepatocyte growth factor receptor MET activity by sorting nexins 1/2 in HCT116 colorectal cancer cells. (PMID:38836326)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx1a	ENSDARG00000071031
		ENSDARG00000103529
mus_musculus	Snx1	ENSMUSG00000032382
rattus_norvegicus	LOC102549158	ENSRNOG00000017029

Paralogs (15): SNX11 (ENSG00000002919), SNX10 (ENSG00000086300), SNX5 (ENSG00000089006), SNX8 (ENSG00000106266), SNX3 (ENSG00000112335), 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-1 — Q13596 (reviewed: Q13596)

All UniProt accessions (8): Q13596, H0YK42, H0YK43, H0YK58, H0YKD5, H0YKL5, H0YKT3, J3KPH4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity. Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin stxB. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi. Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R. Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN. Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking.

Subunit / interactions. Predominantly forms heterodimers with BAR domain-containing sorting nexins SNX5, SNX6 and SNX32; can self-associate to form homodimers. The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS) and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. Interacts with SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35, DRD5, DENND5A, KALRN, RHOG (GDP-bound form). The interaction with SNX2 is reported controversially. Interacts with DNAJC13; prevented by presence of HGS. Interacts with HGS.

Subcellular location. Endosome membrane. Golgi apparatus. trans-Golgi network membrane. Early endosome membrane. Cell projection. Lamellipodium.

Domain organisation. The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of a N-terminal amphipathic helix (AH) in the membrane.

Miscellaneous. Binds phosphatidylinositol 3-phosphate (PtdIns-(3)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2) in liposome-based assays. Can bind PtdIns(3,4,5)P3 in protein:lipid overlay assays, but not in liposome-based assays.

Similarity. Belongs to the sorting nexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13596-1	1	yes
Q13596-2	1A
Q13596-3	3

RefSeq proteins (3): NP_001229862, NP_003090, NP_683758 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR005329	Sorting_nexin_N	Domain
IPR015404	Vps5_C	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR028660	SNX1_BAR	Domain
IPR034901	PX_SNX1	Domain
IPR036871	PX_dom_sf	Homologous_superfamily

Pfam: PF00787, PF03700, PF09325

UniProt features (47 total): modified residue 9, helix 7, mutagenesis site 5, strand 5, binding site 4, region of interest 3, sequence conflict 3, compositionally biased region 3, domain 2, splice variant 2, sequence variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8A1G	X-RAY DIFFRACTION	2.5
4FZS	X-RAY DIFFRACTION	2.8
8ABQ	X-RAY DIFFRACTION	2.81
8AFZ	ELECTRON MICROSCOPY	10
2I4K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13596-F1	76.19	0.60

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): 188; 214; 238; 186

Post-translational modifications (9): 32, 39, 41, 48, 58, 72, 188, 237, 280

Mutagenesis-validated functional residues (5):

Position	Phenotype
214	abolishes phosphatidylinositol phosphate binding. abolishes endosomal location.
287–288	abolishes membrane remodeling capacity; no effect on dimerization.
429–431	loss of endosomal location.
442	no effect on membrane remodeling and membrane binding; when associated with a-445.
445	no effect on membrane remodeling and membrane binding; when associated with a-442.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 287 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, RRAGTTGT_UNKNOWN, GOBP_ENDOSOME_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_45, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_16, AACWWCAANK_UNKNOWN, MODULE_120

GO Biological Process (8): intracellular protein transport (GO:0006886), receptor internalization (GO:0031623), early endosome to Golgi transport (GO:0034498), retrograde transport, endosome to Golgi (GO:0042147), positive regulation of protein catabolic process (GO:0045732), lamellipodium morphogenesis (GO:0072673), protein transport (GO:0015031), endosomal transport (GO:0016197)

GO Molecular Function (11): epidermal growth factor receptor binding (GO:0005154), insulin receptor binding (GO:0005158), phosphatidylinositol binding (GO:0035091), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), protein heterodimerization activity (GO:0046982), transferrin receptor binding (GO:1990459), leptin receptor binding (GO:1990460), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (16): cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endosome membrane (GO:0010008), membrane (GO:0016020), lamellipodium (GO:0030027), retromer complex (GO:0030904), retromer, tubulation complex (GO:0030905), early endosome membrane (GO:0031901), vesicle (GO:0031982), protein-containing complex (GO:0032991), early endosome (GO:0005769), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signaling receptor binding	3
endomembrane system	3
cytoplasm	3
intracellular protein localization	2
intracellular transport	2
protein dimerization activity	2
binding	2
endosome	2
membrane protein complex	2
protein transport	1
receptor-mediated endocytosis	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
lamellipodium organization	1
plasma membrane bounded cell projection morphogenesis	1
transport	1
establishment of protein localization	1
vesicle-mediated transport	1
growth factor receptor binding	1
anion binding	1
protein binding	1
identical protein binding	1
cell adhesion molecule binding	1
intracellular anatomical structure	1
lytic vacuole	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cell leading edge	1
plasma membrane bounded cell projection	1
retromer complex	1

Protein interactions and networks

STRING

2088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX1	VPS26A	O75436	999
SNX1	VPS35	Q96QK1	999
SNX1	VPS29	Q9UBQ0	999
SNX1	SNX6	Q9UNH7	992
SNX1	SNX5	Q9Y5X3	991
SNX1	SNX27	Q96L92	987
SNX1	SNX2	P82862	984
SNX1	SNX4	O95219	976
SNX1	SNX32	Q86XE0	965
SNX1	SERPINE2	P07093	922
SNX1	DNAJC13	O75165	917
SNX1	SNX17	Q15036	909
SNX1	VPS26B	Q4G0F5	892
SNX1	SNX15	Q9NRS6	881
SNX1	IFT122	Q9HBG6	842

IntAct

258 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
SNX6	SNX1	psi-mi:“MI:0914”(association)	0.880
SNX1	SNX6	psi-mi:“MI:0915”(physical association)	0.880
SNX6	SNX1	psi-mi:“MI:0915”(physical association)	0.880
SNX1	SNX32	psi-mi:“MI:0915”(physical association)	0.870
STAM	HGS	psi-mi:“MI:0914”(association)	0.860
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
SNX6	SNX2	psi-mi:“MI:0914”(association)	0.800
SNX1	SNX2	psi-mi:“MI:0914”(association)	0.740
SNX32	SNX2	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ARL6IP1	SNX1	psi-mi:“MI:0915”(physical association)	0.670
REEP6	SNX1	psi-mi:“MI:0915”(physical association)	0.670
SNX1	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.670
SNX1	REEP6	psi-mi:“MI:0915”(physical association)	0.670
FXR2	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
NCKIPSD	GEMIN2	psi-mi:“MI:0914”(association)	0.640

BioGRID (316): RTN3 (Two-hybrid), RABAC1 (Two-hybrid), ARL6IP1 (Two-hybrid), AGTRAP (Two-hybrid), RTN4 (Two-hybrid), REEP6 (Two-hybrid), CMTM5 (Two-hybrid), FUNDC1 (Two-hybrid), SNX32 (Two-hybrid), SNX1 (Affinity Capture-RNA), SNX1 (Affinity Capture-RNA), SNX1 (Affinity Capture-MS), SNX1 (Affinity Capture-MS), SNX1 (Affinity Capture-MS), SNX1 (Affinity Capture-MS)

ESM2 similar proteins: A0A178VBJ0, A7YY57, B9DFS6, F4IHJ0, F4JVA6, O60749, P0C220, Q05B62, Q08DK5, Q13596, Q2TBW7, Q2UB56, Q3KR97, Q3UQN2, Q4R503, Q4WZF1, Q501H5, Q502I9, Q52LW3, Q5PPJ9, Q5R9A9, Q5RFP8, Q5ZJ81, Q6C9X0, Q7SB97, Q8GX47, Q8I4E2, Q8L5Z7, Q8L7W0, Q8LF20, Q8R3V5, Q8S3U9, Q8S9J8, Q93YU8, Q93ZE9, Q99N27, Q9AQW1, Q9C865, Q9CWK8, Q9DBJ3

Diamond homologs: A0A1B7YDZ4, B9DFS6, I1RXT2, O14243, O60107, O60493, O60749, O70492, O70493, O94291, P0C220, P0CR60, P0CR61, P0CR62, P0CR63, Q05B62, Q08826, Q13596, Q1RMH8, Q2TBW7, Q2U4K2, Q3MPQ4, Q4R503, Q4WQI6, Q4WWS3, Q522W5, Q5A748, Q5B797, Q5R5V1, Q5R9A9, Q5RFP8, Q5U211, Q6FT03, Q75CC3, Q7SB54, Q7SB97, Q7SGV1, Q8I4E2, Q8L5Z7, Q91VH2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2091 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64096170:GTC:G	donor_gain	1.0000
15:64096173:G:GG	donor_gain	1.0000
15:64112567:TTTCA:T	acceptor_loss	1.0000
15:64112571:A:AG	acceptor_gain	1.0000
15:64112571:AG:A	acceptor_loss	1.0000
15:64112572:G:GA	acceptor_gain	1.0000
15:64112572:GA:G	acceptor_gain	1.0000
15:64112572:GAGT:G	acceptor_gain	1.0000
15:64112572:GAGTA:G	acceptor_gain	1.0000
15:64118241:GGAG:G	donor_gain	1.0000
15:64118242:G:GT	donor_gain	1.0000
15:64118242:GAGG:G	donor_loss	1.0000
15:64118243:AGGTG:A	donor_loss	1.0000
15:64118244:GGTGA:G	donor_loss	1.0000
15:64118245:G:C	donor_loss	1.0000
15:64118246:T:A	donor_loss	1.0000
15:64118780:T:TA	acceptor_gain	1.0000
15:64126069:T:A	acceptor_gain	1.0000
15:64126076:A:AG	acceptor_gain	1.0000
15:64126077:A:AG	acceptor_gain	1.0000
15:64126078:G:GG	acceptor_gain	1.0000
15:64126078:GACA:G	acceptor_gain	1.0000
15:64126078:GACAA:G	acceptor_gain	1.0000
15:64127160:A:AG	acceptor_gain	1.0000
15:64127161:A:AG	acceptor_gain	1.0000
15:64127162:A:G	acceptor_gain	1.0000
15:64127163:T:G	acceptor_gain	1.0000
15:64127167:A:AG	acceptor_gain	1.0000
15:64127168:T:G	acceptor_gain	1.0000
15:64127169:TCTA:T	acceptor_loss	1.0000

AlphaMissense

3447 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64126122:G:C	R185T	1.000
15:64126123:A:C	R185S	1.000
15:64126123:A:T	R185S	1.000
15:64126125:G:C	R186T	1.000
15:64126125:G:T	R186I	1.000
15:64126127:T:C	F187L	1.000
15:64126129:T:A	F187L	1.000
15:64126129:T:G	F187L	1.000
15:64127790:T:C	F264S	1.000
15:64129980:C:A	A291D	1.000
15:64123520:T:G	Y162D	0.999
15:64123529:T:G	Y165D	0.999
15:64123536:T:A	V167D	0.999
15:64126121:A:G	R185G	0.999
15:64126122:G:T	R185I	0.999
15:64126124:A:G	R186G	0.999
15:64126126:A:C	R186S	0.999
15:64126126:A:T	R186S	0.999
15:64126128:T:C	F187S	0.999
15:64126208:A:C	K214Q	0.999
15:64126208:A:G	K214E	0.999
15:64126210:G:C	K214N	0.999
15:64126210:G:T	K214N	0.999
15:64127190:A:C	K223N	0.999
15:64127190:A:T	K223N	0.999
15:64127221:T:C	F234L	0.999
15:64127223:T:A	F234L	0.999
15:64127223:T:G	F234L	0.999
15:64127234:G:C	R238P	0.999
15:64127789:T:C	F264L	0.999

dbSNP variants (sampled 300 via entrez): RS1000035848 (15:64126009 A>G), RS1000039576 (15:64132322 T>C), RS1000073428 (15:64143864 T>G), RS1000138014 (15:64132175 C>A,G), RS1000160225 (15:64109246 G>A,T), RS1000221412 (15:64126243 C>T), RS1000245705 (15:64108099 A>G), RS1000285037 (15:64095093 G>A), RS1000363378 (15:64144313 G>A,C), RS1000413519 (15:64132524 C>G,T), RS1000488513 (15:64101409 A>G), RS1000529202 (15:64120782 A>G), RS1000551114 (15:64096816 C>A,T), RS1000557290 (15:64120562 A>C,G), RS1000594240 (15:64114024 A>G)

Disease associations

OMIM: gene MIM:601272 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067415 (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
7.75	Kd	17.67	nM	CHEMBL5653589
7.75	ED50	17.67	nM	CHEMBL5653589

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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149462: Binding affinity to human SNX1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0177	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	affects binding, increases reaction, decreases expression, affects cotreatment, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance, decreases methylation	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
methylselenic acid	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
tetrahydropalmatine	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	increases expression	1
Clozapine	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Selenium	increases expression	1
Smoke	decreases expression	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
CHEMBL5652504	Binding	Binding affinity to human SNX1 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

Clinical trials (associated diseases)

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