SNX15

Summary

SNX15 (sorting nexin 15, HGNC:14978) is a protein-coding gene on chromosome 11q13.1, encoding Sorting nexin-15 (Q9NRS6). May be 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. Overexpression of this gene results in a decrease in the processing of insulin and hepatocyte growth factor receptors to their mature subunits. This decrease is caused by the mislocalization of furin, the endoprotease responsible for cleavage of insulin and hepatocyte growth factor receptors. This protein is involved in endosomal trafficking from the plasma membrane to recycling endosomes or the trans-Golgi network. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ADP-ribosylation factor-like 2 (ARL2) gene.

Source: NCBI Gene 29907 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_013306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14978
Approved symbol	SNX15
Name	sorting nexin 15
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000110025
Ensembl biotype	protein_coding
OMIM	605964
Entrez	29907

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000352068, ENST00000377244, ENST00000524831, ENST00000525648, ENST00000526702, ENST00000529673, ENST00000534637, ENST00000880879, ENST00000880880, ENST00000880881, ENST00000880882, ENST00000880883, ENST00000927432

RefSeq mRNA: 2 — MANE Select: NM_013306 NM_013306, NM_147777

CCDS: CCDS8089, CCDS8090

Canonical transcript exons

ENST00000377244 — 8 exons

Exon	Start	End
ENSE00001404377	65027439	65027636
ENSE00001518103	65039686	65040572
ENSE00003500480	65038572	65038829
ENSE00003504591	65034847	65034962
ENSE00003597437	65032431	65032551
ENSE00003616074	65032168	65032203
ENSE00003617798	65035059	65035206
ENSE00003787387	65035520	65035663

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7021 / max 40.9940, expressed in 1783 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115014	7.8034	1767
115015	0.8987	572

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	95.53	gold quality
colonic epithelium	UBERON:0000397	89.82	gold quality
prefrontal cortex	UBERON:0000451	89.32	gold quality
bone marrow	UBERON:0002371	89.20	gold quality
mucosa of transverse colon	UBERON:0004991	89.05	gold quality
granulocyte	CL:0000094	88.23	gold quality
cerebellar hemisphere	UBERON:0002245	88.18	gold quality
cerebellum	UBERON:0002037	88.17	gold quality
cerebellar cortex	UBERON:0002129	88.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.02	gold quality
leukocyte	CL:0000738	87.95	gold quality
monocyte	CL:0000576	87.94	gold quality
frontal cortex	UBERON:0001870	87.86	gold quality
skeletal muscle tissue	UBERON:0001134	87.80	gold quality
gastrocnemius	UBERON:0001388	87.52	gold quality
popliteal artery	UBERON:0002250	87.23	gold quality
tibial artery	UBERON:0007610	87.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.14	gold quality
transverse colon	UBERON:0001157	87.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.00	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.97	gold quality
lower esophagus	UBERON:0013473	86.95	gold quality
cerebral cortex	UBERON:0000956	86.76	gold quality
right coronary artery	UBERON:0001625	86.74	gold quality
muscle of leg	UBERON:0001383	86.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.60	gold quality
colon	UBERON:0001155	86.58	gold quality
cortical plate	UBERON:0005343	86.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.58	gold quality
right frontal lobe	UBERON:0002810	86.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting SNX15, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-6799-5P	99.14	65.72	2093

Literature-anchored findings (GeneRIF, showing 2)

• The activated EGF receptor enters distinct sub-populations of SNX15- and APPL1-labelled peripheral endocytic vesicles. (PMID:23986476)
• SNX15 regulates the recycling of APP to cell surface and, thus, its processing for Abeta generation. (PMID:26115702)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx15	ENSDARG00000020397
mus_musculus	Snx15	ENSMUSG00000024787
rattus_norvegicus	Snx15	ENSRNOG00000021007

Paralogs (2): RPS6KC1 (ENSG00000136643), RPS6KL1 (ENSG00000198208)

Protein

Protein identifiers

Sorting nexin-15 — Q9NRS6 (reviewed: Q9NRS6)

All UniProt accessions (6): Q9NRS6, E5KQS5, E9PK26, E9PMW6, E9PNI5, E9PR81

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in several stages of intracellular trafficking. Overexpression of SNX15 disrupts the normal trafficking of proteins from the plasma membrane to recycling endosomes or the TGN.

Subunit / interactions. Homodimer. Interacts with SNX1, SNX2 and SNX4.

Subcellular location. Cytoplasm. Membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Widely expressed.

Domain organisation. The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate.

Similarity. Belongs to the sorting nexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRS6-1	1	yes
Q9NRS6-2	2, SNX15A

RefSeq proteins (2): NP_037438, NP_680086 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR007330	MIT_dom	Domain
IPR036181	MIT_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR051866	Intracell_Sig-Traffick_Protein	Family

Pfam: PF00787, PF04212

UniProt features (22 total): helix 4, binding site 4, modified residue 3, strand 3, domain 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6ECM	X-RAY DIFFRACTION	2.35
6MBI	X-RAY DIFFRACTION	2.83

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRS6-F1	73.21	0.41

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): 51; 53; 87; 96

Post-translational modifications (3): 227, 105, 201

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): GCM_GSPT1, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, chr11q13, NFKB_C, TGCTGAY_UNKNOWN, GCM_NF2, HOXA4_Q2, TGGAAA_NFAT_Q4_01, BENPORATH_MYC_MAX_TARGETS, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, CACTGCC_MIR34A_MIR34C_MIR449, GCM_RAN

GO Biological Process (2): intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (3): phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (7): nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein localization	2
binding	2
cytoplasm	2
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
anion binding	1
nuclear lumen	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX15	SNX1	Q13596	881
SNX15	SNX4	O95219	803
SNX15	SNX2	P82862	785
SNX15	FIP1L1	Q6UN15	666
SNX15	PDGFC	Q9NRA1	637
SNX15	SNX17	Q15036	629
SNX15	SNX33	Q8WV41	608
SNX15	SNX12	Q9UMY4	601
SNX15	SNX6	Q9UNH7	595
SNX15	SNX3	O60493	590
SNX15	SERPINE2	P07093	573
SNX15	SNX27	Q96L92	571
SNX15	SNX16	P57768	561
SNX15	SNX9	Q9Y5X1	549
SNX15	SNX8	Q9Y5X2	543

IntAct

31 interactions, top by confidence:

A	B	Type	Score
REEP6	SNX15	psi-mi:“MI:0915”(physical association)	0.740
SNX15	REEP6	psi-mi:“MI:0915”(physical association)	0.740
SNX15	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.670
SNX15	RTN4	psi-mi:“MI:0915”(physical association)	0.670
SNX15	RABAC1	psi-mi:“MI:0915”(physical association)	0.670
RTN4	SNX15	psi-mi:“MI:0915”(physical association)	0.670
ARL6IP1	SNX15	psi-mi:“MI:0915”(physical association)	0.670
RABAC1	SNX15	psi-mi:“MI:0915”(physical association)	0.670
SNX15	NT5C2	psi-mi:“MI:0915”(physical association)	0.590
REEP6	SNX15	psi-mi:“MI:0915”(physical association)	0.560
SNX15	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.400
SNX15	CRNN	psi-mi:“MI:0915”(physical association)	0.400
SNX15	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
HOXC10	TRMU	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
ATP5F1C	EI24	psi-mi:“MI:0914”(association)	0.350
SNX15	REEP6	psi-mi:“MI:0915”(physical association)	0.000
SARAF	SNX15	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): SNX15 (Two-hybrid), SNX15 (Two-hybrid), RTN4 (Two-hybrid), REEP6 (Two-hybrid), SNX15 (Two-hybrid), RTN4 (Two-hybrid), REEP6 (Two-hybrid), SNX15 (Affinity Capture-MS), NT5C2 (Affinity Capture-MS), SNX15 (Proximity Label-MS), REEP6 (Two-hybrid), SNX15 (Proximity Label-MS), SNX15 (Affinity Capture-MS), NT5C2 (Affinity Capture-MS), CRNN (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A3R064, A4D2P6, A7MBB8, B2DCZ9, B2RYG7, O08773, O43566, O60496, O70469, P52734, P70268, P97465, P97492, P98174, Q0QWG9, Q14451, Q148E7, Q14B98, Q16512, Q1RMU7, Q3B7L1, Q3UYI5, Q4QQV2, Q5EA84, Q63433, Q6ICB4, Q6P5Z2, Q6PFY1, Q6V7V2, Q7L591, Q7Z5H3, Q865S3, Q86WN1, Q8BH49, Q8C6B2, Q8K045, Q8NFA2, Q8R4L0, Q8TE68

Diamond homologs: Q148E7, Q3UR97, Q4V896, Q5RA67, Q8BLK9, Q8R2S1, Q91WE1, Q96S38, Q9C0U7, Q9NRS6, Q9Y6S9, D3ZHP7, Q5AG40, Q6PHR2, A1Z9X0, A7MBL8, A8KBH6, A8XJQ6, F4HPN2, G1X456, M3TYT0, O01583, O08874, O19111, O54874, O70293, O75582, O75676, O77819, P05130, P05986, P06244, P06245, P09217, P10665, P10666, P16911, P18652, P18653, P18654

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1302 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65027619:TACA:T	donor_gain	1.0000
11:65027620:ACAA:A	donor_gain	1.0000
11:65027635:AG:A	donor_loss	1.0000
11:65027636:GG:G	donor_loss	1.0000
11:65031513:G:T	donor_gain	1.0000
11:65032164:TCA:T	acceptor_loss	1.0000
11:65032165:CAG:C	acceptor_loss	1.0000
11:65032166:A:AG	acceptor_gain	1.0000
11:65032166:A:C	acceptor_loss	1.0000
11:65032166:AG:A	acceptor_loss	1.0000
11:65032167:G:GA	acceptor_gain	1.0000
11:65032167:GTT:G	acceptor_gain	1.0000
11:65032167:GTTC:G	acceptor_gain	1.0000
11:65032547:GTTTG:G	donor_gain	1.0000
11:65032549:TTGGT:T	donor_loss	1.0000
11:65032552:G:GG	donor_gain	1.0000
11:65032552:GT:G	donor_loss	1.0000
11:65032553:T:A	donor_loss	1.0000
11:65034823:T:TA	acceptor_gain	1.0000
11:65034830:T:A	acceptor_gain	1.0000
11:65034830:T:TA	acceptor_gain	1.0000
11:65034835:T:A	acceptor_gain	1.0000
11:65034835:T:TA	acceptor_gain	1.0000
11:65034836:G:A	acceptor_gain	1.0000
11:65034845:AGGCC:A	acceptor_gain	1.0000
11:65034846:GGC:G	acceptor_gain	1.0000
11:65034846:GGCCG:G	acceptor_gain	1.0000
11:65034961:GG:G	donor_gain	1.0000
11:65034961:GGGTA:G	donor_loss	1.0000
11:65034962:GG:G	donor_gain	1.0000

AlphaMissense

2196 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65027619:T:C	Y28H	0.999
11:65032480:T:C	L62P	0.999
11:65027619:T:G	Y28D	0.998
11:65027620:A:C	Y28S	0.998
11:65032459:T:C	F55S	0.998
11:65032491:C:G	H66D	0.998
11:65034852:T:C	F88L	0.998
11:65034854:T:A	F88L	0.998
11:65034854:T:G	F88L	0.998
11:65034880:G:C	R97P	0.998
11:65034906:T:C	F106L	0.998
11:65034908:C:A	F106L	0.998
11:65034908:C:G	F106L	0.998
11:65034928:T:A	L113H	0.998
11:65034928:T:C	L113P	0.998
11:65034936:A:C	S116R	0.998
11:65034938:C:A	S116R	0.998
11:65034938:C:G	S116R	0.998
11:65034954:T:C	F122L	0.998
11:65034956:C:A	F122L	0.998
11:65034956:C:G	F122L	0.998
11:65032449:T:G	Y52D	0.997
11:65032468:T:C	L58P	0.997
11:65032503:T:C	F70L	0.997
11:65032505:C:A	F70L	0.997
11:65032505:C:G	F70L	0.997
11:65032521:T:C	F76L	0.997
11:65032522:T:C	F76S	0.997
11:65032523:C:A	F76L	0.997
11:65032523:C:G	F76L	0.997

dbSNP variants (sampled 300 via entrez): RS1000145233 (11:65040295 G>A), RS1000403597 (11:65029023 G>A), RS1000836170 (11:65028709 CAAAT>C), RS1000899600 (11:65027283 C>A,G), RS1000908777 (11:65033078 A>G), RS1001023139 (11:65032816 A>G), RS1001143077 (11:65038910 C>A,T), RS1001296983 (11:65039539 T>C,G), RS1001328180 (11:65038981 T>C), RS1001581550 (11:65029350 G>C), RS1001644668 (11:65033186 C>T), RS1002319951 (11:65027786 T>A,C,G), RS1002460251 (11:65033479 G>A), RS1002612505 (11:65030363 T>A), RS1002922547 (11:65030282 G>A)

Disease associations

OMIM: gene MIM:605964 | 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: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases abundance, increases expression	2
Valproic Acid	affects expression, increases methylation	2
bisphenol F	affects cotreatment, increases expression	1
decabromobiphenyl ether	affects expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
S-Nitrosoglutathione	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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