SNX5

Summary

SNX5 (sorting nexin 5, HGNC:14969) is a protein-coding gene on chromosome 20p11.23, encoding Sorting nexin-5 (Q9Y5X3). 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 protein functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 27131 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_014426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14969
Approved symbol	SNX5
Name	sorting nexin 5
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000089006
Ensembl biotype	protein_coding
OMIM	605937
Entrez	27131

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 8 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000377759, ENST00000377768, ENST00000419004, ENST00000431277, ENST00000463050, ENST00000469704, ENST00000474883, ENST00000475716, ENST00000476648, ENST00000481323, ENST00000483485, ENST00000484809, ENST00000486039, ENST00000490175, ENST00000491090, ENST00000494401, ENST00000606557, ENST00000606570, ENST00000606602, ENST00000895746, ENST00000895747, ENST00000895748, ENST00000895749, ENST00000925824, ENST00000970421

RefSeq mRNA: 3 — MANE Select: NM_014426 NM_001282454, NM_014426, NM_152227

CCDS: CCDS13130

Canonical transcript exons

ENST00000377759 — 13 exons

Exon	Start	End
ENSE00001873876	17968375	17968794
ENSE00003482574	17951500	17951595
ENSE00003484405	17953996	17954117
ENSE00003485654	17947486	17947645
ENSE00003536847	17952587	17952710
ENSE00003541583	17949064	17949103
ENSE00003602968	17955365	17955475
ENSE00003641825	17943110	17943195
ENSE00003649696	17950291	17950396
ENSE00003655933	17956933	17957037
ENSE00003717933	17950132	17950207
ENSE00003784161	17948890	17948976
ENSE00003904320	17941600	17942407

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.3599 / max 553.9949, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186532	60.6637	1821
186529	11.1509	1727
186530	10.0694	1753
186528	0.8099	425
186531	0.3599	173
186524	0.1559	53
186523	0.1503	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left lobe of thyroid gland	UBERON:0001120	98.48	gold quality
adrenal tissue	UBERON:0018303	98.42	gold quality
right lobe of thyroid gland	UBERON:0001119	98.41	gold quality
thyroid gland	UBERON:0002046	98.38	gold quality
ventricular zone	UBERON:0003053	98.30	gold quality
calcaneal tendon	UBERON:0003701	98.17	gold quality
rectum	UBERON:0001052	98.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.02	gold quality
spleen	UBERON:0002106	98.01	gold quality
corpus epididymis	UBERON:0004359	97.92	gold quality
secondary oocyte	CL:0000655	97.88	gold quality
lymph node	UBERON:0000029	97.57	gold quality
left ovary	UBERON:0002119	97.57	gold quality
right adrenal gland cortex	UBERON:0035827	97.46	gold quality
left adrenal gland cortex	UBERON:0035825	97.39	gold quality
right ovary	UBERON:0002118	97.36	gold quality
right adrenal gland	UBERON:0001233	97.35	gold quality
left adrenal gland	UBERON:0001234	97.35	gold quality
metanephros cortex	UBERON:0010533	97.32	gold quality
adult mammalian kidney	UBERON:0000082	97.23	gold quality
adrenal gland	UBERON:0002369	97.23	gold quality
adrenal cortex	UBERON:0001235	97.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.00	gold quality
monocyte	CL:0000576	96.95	gold quality
ovary	UBERON:0000992	96.94	gold quality
tendon	UBERON:0000043	96.89	gold quality
ganglionic eminence	UBERON:0004023	96.83	gold quality
gall bladder	UBERON:0002110	96.77	gold quality
vermiform appendix	UBERON:0001154	96.73	gold quality
mononuclear cell	CL:0000842	96.63	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	10.26
E-MTAB-9801	yes	7.09
E-CURD-53	no	303.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting SNX5, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Literature-anchored findings (GeneRIF, showing 17)

• SNX5 is localized to a subdomain of the early endosomes and is recruited to the cell membrane following EGF stimulation. (PMID:15561769)
• SNX5 and SNX6 may constitute functional equivalents of Vps17p in mammalian retromer (PMID:17148574)
• DOCK180 regulates CI-MPR trafficking via SNX5 and this function is independent of its guanine nucleotide exchange factor activity toward Rac1 (PMID:18596235)
• Data indicate induction of caspase-2 by sorting nexin 5 (SNX5) in papillary thyroid carcinoma (PMID:22486813)
• internalization of agonist-activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the receptor to the plasma membrane (PMID:23195037)
• Sorting nexin 5 and dopamine d1 receptor regulate the expression of the insulin receptor in human renal proximal tubule cells (PMID:25825816)
• The Chlamydia trachomatis IncE binding site is unique to human SNX5 and related family members SNX6 and SNX32. (PMID:28226239)
• sorting nexin 5 (SNX5), a component of the retromer and part of the retrograde transport pathway, interacts with UL35 proteins. binding of UL35 proteins to SNX5 was required for efficient viral replication and for transport of the most abundant cytomegalovirus glycoprotein B to the cytoplasmic viral assembly center. (PMID:29444945)
• High SNX5 expression is associated with alphavirus infections. (PMID:29743363)
• Results indicate that SNX5 constitutive phosphorylation that mimics the mutant S226E decreases the active SNX5 in these cells. The phosphorylation of SNX5 regulates the dimerization with SNX1 or SNX2, and this suggests that it controls membrane trafficking and protein sorting. (PMID:30419003)
• The studies identify a sorting motif and provide molecular insight into an evolutionary conserved coat complex, the ‘Endosomal SNX-BAR sorting complex for promoting exit 1’ (ESCPE-1), which couples sorting motif recognition to the BAR-domain-mediated biogenesis of cargo-enriched tubulo-vesicular transport carriers. (PMID:31576058)
• SNX5 inhibits RLR-mediated antiviral signaling by targeting RIG-I-VISA signalosome. (PMID:31806368)
• Upregulation of SNX5 predicts poor prognosis and promotes hepatocellular carcinoma progression by modulating the EGFR-ERK1/2 signaling pathway. (PMID:31819169)
• Sorting nexin 5 mediates virus-induced autophagy and immunity. (PMID:33328639)
• Overexpression of lncRNA HOXA-AS2 promotes the progression of oral squamous cell carcinoma by mediating SNX5 expression. (PMID:36528556)
• The association of lipid transfer protein VPS13A with endosomes is mediated by sorting nexin SNX5. (PMID:36977596)
• SNX5 promotes antigen presentation in B cells by dual regulation of actin and lysosomal dynamics. (PMID:39448266)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx5	ENSDARG00000020442
mus_musculus	Snx5	ENSMUSG00000027423
rattus_norvegicus	Snx5	ENSRNOG00000006077
drosophila_melanogaster	Snx1	FBGN0031534
drosophila_melanogaster	Snx6	FBGN0032005
caenorhabditis_elegans		WBGENE00004927
caenorhabditis_elegans		WBGENE00013354

Paralogs (15): SNX11 (ENSG00000002919), SNX1 (ENSG00000028528), SNX10 (ENSG00000086300), 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-5 — Q9Y5X3 (reviewed: Q9Y5X3)

All UniProt accessions (7): Q9Y5X3, A0A087WUY5, A0A0S2Z5F1, Q5QPE4, Q5QPE5, U3KQL0, U3KQP5

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 3,4-bisphosphate (PtdIns(3,4)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). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin. Plays a role in the internalization of EGFR after EGF stimulation. Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent. Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation. Plays a role in macropinocytosis.

Subunit / interactions. Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2; does not homodimerize. Interacts with SNX32. 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 SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C isoform 3. Interacts with HGS; increased by PIP5K1C isoform 3 kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2. (Microbial infection) Interacts with human cytomegalovirus proteins UL35 and UL35A; these interactions inhibit the ability of USP7 to form nuclear bodies.

Subcellular location. Endosome. Early endosome. Early endosome membrane. Cell membrane. Cytoplasmic vesicle membrane. Cytoplasm. Cell projection. Phagocytic cup. Ruffle.

Domain organisation. The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate. The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane.

Similarity. Belongs to the sorting nexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5X3-1	1	yes
Q9Y5X3-2	2

RefSeq proteins (3): NP_001269383, NP_055241, NP_689413 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR014637	SNX5/SNX6/SNX32	Family
IPR015404	Vps5_C	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR028654	BAR_SNX5	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR042135	PX_SNX5	Domain

Pfam: PF00787, PF09325

UniProt features (41 total): helix 12, mutagenesis site 8, strand 6, modified residue 3, binding site 3, splice variant 2, domain 2, region of interest 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
5WY2	X-RAY DIFFRACTION	1.9
5TGI	X-RAY DIFFRACTION	1.98
6N5X	X-RAY DIFFRACTION	2.05
6N5Y	X-RAY DIFFRACTION	2.26
9IAE	X-RAY DIFFRACTION	2.3
9IGY	X-RAY DIFFRACTION	2.3
1SYS	X-RAY DIFFRACTION	2.4
6N5Z	X-RAY DIFFRACTION	2.45
8A1G	X-RAY DIFFRACTION	2.5
5TGJ	X-RAY DIFFRACTION	2.6
5TGH	X-RAY DIFFRACTION	2.8
8ABQ	X-RAY DIFFRACTION	2.81
8AFZ	ELECTRON MICROSCOPY	10

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5X3-F1	87.23	0.72

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): 40–46; 99–105; 113–116

Post-translational modifications (3): 193, 275, 2

Mutagenesis-validated functional residues (8):

Position	Phenotype
186–187	no effect on dimerization.
224	decreaes phosphoinositide binding, including ptdins(3,4)p2 and ptdins(3p); when associated with e-235, e-324, e-328 and
235	decreaes phosphoinositide binding, including ptdins(3,4)p2 and ptdins(3p); when associated with e-224, e-324, e-328 and
280	enables homodimerization; when associated with a-383.
324	decreaes phosphoinositide binding, including ptdins(3,4)p2 and ptdins(3p); when associated with e-224, e-235, e-328 and
328	decreaes phosphoinositide binding, including ptdins(3,4)p2 and ptdins(3p); when associated with e-224, e-235, e-324 and
330	decreaes phosphoinositide binding, including ptdins(3,4)p2 and ptdins(3p); when associated with e-224, e-235, e-324 and
383	enables homodimerization; when associated with a-280.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 349 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PINOCYTOSIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_ENDOSOME_ORGANIZATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MODULE_255, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_VESICLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (10): intracellular protein transport (GO:0006886), pinocytosis (GO:0006907), epidermal growth factor catabolic process (GO:0007174), regulation of macroautophagy (GO:0016241), retrograde transport, endosome to Golgi (GO:0042147), negative regulation of blood pressure (GO:0045776), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of insulin receptor signaling pathway (GO:0046628), endocytosis (GO:0006897), protein transport (GO:0015031)

GO Molecular Function (9): phosphatidylinositol-5-phosphate binding (GO:0010314), D1 dopamine receptor binding (GO:0031748), dynactin binding (GO:0034452), phosphatidylinositol binding (GO:0035091), cadherin binding (GO:0045296), phosphatidylinositol-4-phosphate binding (GO:0070273), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (20): ruffle (GO:0001726), phagocytic cup (GO:0001891), endosome (GO:0005768), cytosol (GO:0005829), brush border (GO:0005903), cytoplasmic side of plasma membrane (GO:0009898), retromer complex (GO:0030904), retromer, tubulation complex (GO:0030905), perinuclear region of cytoplasm (GO:0048471), macropinocytic cup (GO:0070685), tubular endosome (GO:0097422), cytoplasmic side of early endosome membrane (GO:0098559), cytoplasm (GO:0005737), early endosome (GO:0005769), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), early endosome membrane (GO:0031901), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
anion binding	3
phosphatidylinositol phosphate binding	3
cytoplasm	3
intracellular protein localization	2
binding	2
plasma membrane bounded cell projection	2
plasma membrane	2
endomembrane system	2
cytoplasmic vesicle	2
membrane protein complex	2
endosome	2
protein transport	1
intracellular transport	1
endocytosis	1
protein catabolic process	1
negative regulation of epidermal growth factor receptor signaling pathway	1
regulation of autophagy	1
macroautophagy	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
regulation of blood pressure	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
transport	1
establishment of protein localization	1
dopamine receptor binding	1
cytoskeletal protein binding	1
cell adhesion molecule binding	1
phosphatidylinositol bisphosphate binding	1

Protein interactions and networks

STRING

1210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX5	SNX1	Q13596	991
SNX5	VPS35	Q96QK1	990
SNX5	SNX2	P82862	990
SNX5	VPS26A	O75436	986
SNX5	SNX6	Q9UNH7	984
SNX5	VPS29	Q9UBQ0	980
SNX5	DCTN1	Q14203	932
SNX5	SNX27	Q96L92	919
SNX5	SNX3	O60493	894
SNX5	SERPINE2	P07093	879
SNX5	SNX4	O95219	845
SNX5	IGF2R	P11717	834
SNX5	SNX32	Q86XE0	800
SNX5	SNX17	Q15036	794
SNX5	SNX12	Q9UMY4	781

IntAct

113 interactions, top by confidence:

A	B	Type	Score
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
SNX1	SNX2	psi-mi:“MI:0914”(association)	0.740
SNX1	SNX5	psi-mi:“MI:0915”(physical association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STK4	STRN	psi-mi:“MI:2364”(proximity)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
APPBP2	SNX5	psi-mi:“MI:0915”(physical association)	0.560
SNX5	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
SNX2	SNX5	psi-mi:“MI:0915”(physical association)	0.550
SNX5	SNX2	psi-mi:“MI:0914”(association)	0.550
SNX5	DNAJB11	psi-mi:“MI:0915”(physical association)	0.550
FAM221A	SNX2	psi-mi:“MI:0914”(association)	0.530
C11orf42	SNX2	psi-mi:“MI:0914”(association)	0.530
HCLS1	SNX1	psi-mi:“MI:0914”(association)	0.530
BIN3	ARHGEF37	psi-mi:“MI:0914”(association)	0.530
FAM90A1	RFPL4A	psi-mi:“MI:0914”(association)	0.530
BLVRA	DDHD2	psi-mi:“MI:0914”(association)	0.530
KLHL10	HSPA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (203): SNX5 (Two-hybrid), SNX5 (Two-hybrid), SNX5 (Affinity Capture-Western), PIP5K1C (Affinity Capture-Western), LAPTM4B (Affinity Capture-Western), SNX5 (Affinity Capture-Western), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B7YDZ4, B1H267, I1RXT2, O14243, O60107, O74960, O94447, P0CR58, P0CR59, P0CR62, P0CR63, P0CR64, P0CR65, P32912, P32913, P40531, P40959, P47057, Q09746, Q10253, Q28GP7, Q3ZBM5, Q4PHC3, Q4VAA7, Q4WQI6, Q522W5, Q5B797, Q5R613, Q6C238, Q6C9X0, Q6CGJ5, Q6CHY6, Q6CTQ0, Q6CUC4, Q6FPT9, Q6NRL2, Q6P8X1, Q759T1, Q75B65, Q75C43

Diamond homologs: B1H267, Q3ZBM5, Q4V7P7, Q5R613, Q6P8X1, Q80ZJ7, Q86XE0, Q9D8U8, Q9UNH7, Q9Y5X3, B9DFS6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SNX5	“up-regulates activity”	DOCK1	binding
SNX5	“down-regulates quantity”	IGF2R	binding
SNX5	“down-regulates quantity”	IGF1R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2237 predictions. Top by Δscore:

Variant	Effect	Δscore
20:17943108:AC:A	donor_gain	1.0000
20:17943109:CC:C	donor_gain	1.0000
20:17943191:CAGTT:C	acceptor_gain	1.0000
20:17943194:TTCTA:T	acceptor_loss	1.0000
20:17943195:TC:T	acceptor_loss	1.0000
20:17943196:C:CA	acceptor_loss	1.0000
20:17943196:C:CC	acceptor_gain	1.0000
20:17943197:T:A	acceptor_loss	1.0000
20:17947456:CAGTA:C	donor_gain	1.0000
20:17947475:T:TA	donor_gain	1.0000
20:17947483:AAC:A	donor_gain	1.0000
20:17947484:A:C	donor_gain	1.0000
20:17947488:T:TA	donor_gain	1.0000
20:17948886:CTA:C	donor_loss	1.0000
20:17948888:A:C	donor_loss	1.0000
20:17948889:C:A	donor_loss	1.0000
20:17948973:CTTT:C	acceptor_gain	1.0000
20:17948974:TTT:T	acceptor_gain	1.0000
20:17948975:TT:T	acceptor_gain	1.0000
20:17948977:C:CC	acceptor_gain	1.0000
20:17948978:T:C	acceptor_loss	1.0000
20:17948979:A:C	acceptor_gain	1.0000
20:17948981:A:AC	acceptor_gain	1.0000
20:17948981:A:C	acceptor_gain	1.0000
20:17950125:AACTT:A	donor_loss	1.0000
20:17950126:ACTTA:A	donor_loss	1.0000
20:17950127:CTTAC:C	donor_loss	1.0000
20:17950128:TTACT:T	donor_loss	1.0000
20:17950129:TA:T	donor_loss	1.0000
20:17950130:A:AC	donor_gain	1.0000

AlphaMissense

2697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:17943115:C:G	A387P	1.000
20:17943129:A:G	L382P	1.000
20:17943147:A:G	L376P	1.000
20:17943192:A:G	L361P	1.000
20:17950318:C:G	A230P	1.000
20:17952603:A:G	L166P	1.000
20:17952606:A:G	F165S	1.000
20:17952660:A:G	L147P	1.000
20:17952660:A:T	L147H	1.000
20:17952689:C:A	K137N	1.000
20:17952689:C:G	K137N	1.000
20:17952692:A:C	F136L	1.000
20:17952692:A:T	F136L	1.000
20:17952693:A:C	F136C	1.000
20:17952693:A:G	F136S	1.000
20:17952694:A:G	F136L	1.000
20:17952702:A:G	L133P	1.000
20:17952705:T:C	Y132C	1.000
20:17952706:A:G	Y132H	1.000
20:17954002:A:G	L128P	1.000
20:17954010:T:A	K125N	1.000
20:17954010:T:G	K125N	1.000
20:17954104:G:T	P94H	1.000
20:17955408:A:G	L75P	1.000
20:17955412:A:G	W74R	1.000
20:17955412:A:T	W74R	1.000
20:17955431:C:A	R67S	1.000
20:17955431:C:G	R67S	1.000
20:17955432:C:A	R67M	1.000
20:17955432:C:G	R67T	1.000

dbSNP variants (sampled 300 via entrez): RS1000271693 (20:17963724 T>C), RS1000425674 (20:17969607 C>A,G), RS1000470950 (20:17953454 A>G), RS1000657467 (20:17965776 C>T), RS1000782192 (20:17944671 G>A,C), RS1000877238 (20:17943284 G>C), RS1001020714 (20:17961454 G>A,C), RS1001066678 (20:17961703 C>T), RS1001085387 (20:17956446 G>A,T), RS1001092747 (20:17943046 A>C,G), RS1001147707 (20:17948826 G>C,T), RS1001191206 (20:17959087 A>G), RS1001289577 (20:17948096 T>C), RS1001433861 (20:17948514 G>A,C), RS1001570099 (20:17952876 T>C)

Disease associations

OMIM: gene MIM:605937 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002222_47	LDL cholesterol	6.000000e-09
GCST002896_24	Cholesterol, total	2.000000e-12
GCST002898_21	LDL cholesterol	7.000000e-15
GCST004233_18	LDL cholesterol levels	2.000000e-10
GCST008077_84	LDL cholesterol levels	1.000000e-06
GCST008078_119	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-11
GCST008078_15	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-13
GCST008079_109	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-85
GCST008079_38	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-77
GCST008086_42	LDL cholesterol levels in current drinkers	1.000000e-09
GCST008086_61	LDL cholesterol levels in current drinkers	2.000000e-10
GCST010243_181	Apolipoprotein B levels	3.000000e-43
GCST010245_200	LDL cholesterol levels	1.000000e-29
GCST011347_62	Low density lipoprotein cholesterol levels	9.000000e-11
GCST90013405_106	Liver enzyme levels (alanine transaminase)	3.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, affects expression	5
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	3
Valproic Acid	decreases expression, decreases methylation, affects expression	3
bisphenol A	affects expression, decreases expression	2
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	2
Acrolein	increases abundance, affects cotreatment, increases expression	2
Air Pollutants	increases expression, affects expression, affects cotreatment, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
4-phenylbutyric acid	decreases expression	1
ICG 001	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
tianma gouteng yin	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	increases expression	1
Acetylglucosamine	decreases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8VT	Ubigene HCT 116 SNX5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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