SNX11

Summary

SNX11 (sorting nexin 11, HGNC:14975) is a protein-coding gene on chromosome 17q21.32, encoding Sorting nexin-11 (Q9Y5W9). Phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes.

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 some family members. This gene encodes a protein of unknown function. This gene results in two transcript variants differing in the 5’ UTR, but encoding the same protein.

Source: NCBI Gene 29916 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_013323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14975
Approved symbol	SNX11
Name	sorting nexin 11
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000002919
Ensembl biotype	protein_coding
OMIM	614906
Entrez	29916

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000359238, ENST00000393405, ENST00000452859, ENST00000577310, ENST00000578861, ENST00000580219, ENST00000580875, ENST00000581298, ENST00000581705, ENST00000582104, ENST00000582481, ENST00000583320, ENST00000584335, ENST00000883819, ENST00000883820, ENST00000883821, ENST00000883822, ENST00000913721, ENST00000913722, ENST00000913723, ENST00000913724, ENST00000960405, ENST00000960406

RefSeq mRNA: 3 — MANE Select: NM_013323 NM_001330320, NM_013323, NM_152244

CCDS: CCDS11526, CCDS82152

Canonical transcript exons

ENST00000359238 — 7 exons

Exon	Start	End
ENSE00001256504	48121235	48123601
ENSE00001324714	48107766	48107838
ENSE00003509394	48118974	48119186
ENSE00003539166	48118704	48118799
ENSE00003588413	48112031	48112085
ENSE00003589295	48113301	48113401
ENSE00003605195	48112574	48112660

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 93.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1943 / max 177.2784, expressed in 1803 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161421	7.1423	1765
161420	4.7245	1560
161422	0.3275	104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	93.11	silver quality
gingival epithelium	UBERON:0001949	92.88	gold quality
tongue squamous epithelium	UBERON:0006919	92.82	silver quality
pancreatic ductal cell	CL:0002079	92.56	gold quality
monocyte	CL:0000576	92.31	gold quality
leukocyte	CL:0000738	92.20	gold quality
mononuclear cell	CL:0000842	92.13	gold quality
granulocyte	CL:0000094	91.97	gold quality
blood	UBERON:0000178	91.67	gold quality
hair follicle	UBERON:0002073	90.50	silver quality
epithelium of nasopharynx	UBERON:0001951	89.97	gold quality
gingiva	UBERON:0001828	89.48	gold quality
islet of Langerhans	UBERON:0000006	88.83	gold quality
inferior olivary complex	UBERON:0002127	88.51	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.41	gold quality
lower esophagus mucosa	UBERON:0035834	88.35	gold quality
germinal epithelium of ovary	UBERON:0001304	87.62	gold quality
squamous epithelium	UBERON:0006914	87.53	gold quality
lymph node	UBERON:0000029	87.52	gold quality
bone marrow	UBERON:0002371	87.15	gold quality
spleen	UBERON:0002106	87.12	gold quality
tonsil	UBERON:0002372	87.11	gold quality
periodontal ligament	UBERON:0008266	86.97	gold quality
mucosa of transverse colon	UBERON:0004991	86.94	gold quality
epithelial cell of pancreas	CL:0000083	86.92	silver quality
vermiform appendix	UBERON:0001154	86.73	gold quality
bone marrow cell	CL:0002092	86.40	gold quality
caecum	UBERON:0001153	86.40	gold quality
esophagus mucosa	UBERON:0002469	85.83	gold quality
prefrontal cortex	UBERON:0000451	85.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.48

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Structure of sorting nexin 11 (SNX11) reveals a novel extended phox homology (PX) domain critical for inhibition of SNX10-induced vacuolation. (PMID:23615901)
• penetration of Severe fever with thrombocytopenia syndrome virus from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11 (PMID:31215001)
• Molecular Basis for PI(3,5)P2 Recognition by SNX11, a Protein Involved in Lysosomal Degradation and Endosome Homeostasis Regulation. (PMID:32561432)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx11	ENSDARG00000052522
mus_musculus	Snx11	ENSMUSG00000020876
rattus_norvegicus	Snx11	ENSRNOG00000008642
drosophila_melanogaster	Snx1	FBGN0031534
drosophila_melanogaster	Snx6	FBGN0032005
caenorhabditis_elegans		WBGENE00004927
caenorhabditis_elegans		WBGENE00013354

Paralogs (15): SNX1 (ENSG00000028528), 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-11 — Q9Y5W9 (reviewed: Q9Y5W9)

All UniProt accessions (7): Q9Y5W9, B4DJI7, J3KTN6, J3QKV3, J3QLV8, J3QRB9, J3QRW4

UniProt curated annotations — full annotation on UniProt →

Function. Phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Regulates the levels of TRPV3 by promoting its trafficking from the cell membrane to lysosome for degradation.

Subunit / interactions. Monomer. Interacts with TRPV3; this interaction promotes TRPV3 trafficking from the cell membrane to lysosome for degradation.

Subcellular location. Cell membrane. Endosome. Cytoplasm.

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?
Q9Y5W9-1	1	yes
Q9Y5W9-2	2

RefSeq proteins (3): NP_001317249, NP_037455, NP_689450 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR043544	SNX10/11	Family

Pfam: PF00787

UniProt features (25 total): helix 8, strand 5, binding site 3, mutagenesis site 2, region of interest 2, chain 1, domain 1, turn 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4IKD	X-RAY DIFFRACTION	1.6
4IKB	X-RAY DIFFRACTION	1.78
6KOK	X-RAY DIFFRACTION	2
6KOJ	X-RAY DIFFRACTION	2.14
6KOI	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5W9-F1	75.89	0.51

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): 59; 85; 99

Mutagenesis-validated functional residues (2):

Position	Phenotype
135–139	impairs function in membrane trafficking.
59	abolishes lipid-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, BLALOCK_ALZHEIMERS_DISEASE_UP, DOUGLAS_BMI1_TARGETS_DN, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, TCCCRNNRTGC_UNKNOWN, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, VERHAAK_GLIOBLASTOMA_NEURAL, IVANOVSKA_MIR106B_TARGETS, GOBP_INTRACELLULAR_TRANSPORT, TBK1.DF_UP

GO Biological Process (3): intracellular protein transport (GO:0006886), vesicle organization (GO:0016050), protein transport (GO:0015031)

GO Molecular Function (4): phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515), lipid binding (GO:0008289), phosphatidylinositol binding (GO:0035091)

GO Cellular Component (5): cytoplasm (GO:0005737), endosome (GO:0005768), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein localization	2
binding	2
protein transport	1
intracellular transport	1
organelle organization	1
transport	1
establishment of protein localization	1
phospholipid binding	1
anion binding	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX11	SNX24	Q9Y343	638
SNX11	SNX22	Q96L94	614
SNX11	SNX17	Q15036	600
SNX11	SNX21	Q969T3	528
SNX11	CDK5RAP3	Q96JB5	521
SNX11	SNX14	Q9Y5W7	519
SNX11	SNX15	Q9NRS6	519
SNX11	SNX16	P57768	519
SNX11	VPS29	Q9UBQ0	510
SNX11	SNX32	Q86XE0	501
SNX11	SNX27	Q96L92	482
SNX11	SNX33	Q8WV41	477
SNX11	TSNARE1	Q96NA8	475
SNX11	ZER1	Q7Z7L7	474
SNX11	TTLL6	Q8N841	471

IntAct

58 interactions, top by confidence:

A	B	Type	Score
TNFRSF9	TNFSF9	psi-mi:“MI:0914”(association)	0.820
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
SNX11	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
SNX11	RABAC1	psi-mi:“MI:0915”(physical association)	0.720
ARL6IP1	SNX11	psi-mi:“MI:0915”(physical association)	0.720
RABAC1	SNX11	psi-mi:“MI:0915”(physical association)	0.720
RPRM	SNX11	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	SNX11	psi-mi:“MI:0915”(physical association)	0.560
ZMYND10	SNX11	psi-mi:“MI:0915”(physical association)	0.560
SMYD2	SNX11	psi-mi:“MI:0915”(physical association)	0.560
SMYD1	SNX11	psi-mi:“MI:0915”(physical association)	0.560
MAJIN	SNX11	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	SNX11	psi-mi:“MI:0915”(physical association)	0.560
REEP6	SNX11	psi-mi:“MI:0915”(physical association)	0.560
AREG	ADCY9	psi-mi:“MI:0914”(association)	0.530
MRPL16	HSPD1	psi-mi:“MI:0914”(association)	0.530
SNX11	PML	psi-mi:“MI:0914”(association)	0.530
SNX11	FANCL	psi-mi:“MI:0915”(physical association)	0.400
SUSD3	IGLL5	psi-mi:“MI:0914”(association)	0.350
SNX11	CHEK1	psi-mi:“MI:0914”(association)	0.350
GLIPR1L2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
RAB34	RAP1GDS1	psi-mi:“MI:0914”(association)	0.350
PNPLA4	ATP2B3	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): SNX11 (Two-hybrid), SNX11 (Two-hybrid), STK40 (Affinity Capture-MS), NPHP3 (Affinity Capture-MS), PML (Affinity Capture-MS), AP3B1 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), FGFR3 (Affinity Capture-MS), CHEK1 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), PYCRL (Affinity Capture-MS), DCAF10 (Affinity Capture-MS), ORC3 (Affinity Capture-MS), CTU1 (Affinity Capture-MS), C18orf8 (Affinity Capture-MS)

ESM2 similar proteins: A1E2V0, A2AWP0, A6QPT6, A9JTP3, A9ULZ2, B1WBS3, O08863, O14771, O15037, O43918, O94966, P05433, P48778, P51617, Q08DD7, Q0P5G1, Q13077, Q15477, Q2LGB3, Q3TD16, Q3UJD6, Q499Z3, Q4R3B7, Q4R6Y5, Q5RA67, Q5XIS1, Q62210, Q62406, Q6AXX1, Q6J1Y9, Q75NR7, Q80U38, Q80VL3, Q811H0, Q8BHW9, Q8CFK6, Q8JHV9, Q8K330, Q8R2S1, Q8TE77

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1039 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48112569:TACAG:T	acceptor_loss	1.0000
17:48112571:CA:C	acceptor_loss	1.0000
17:48112572:A:C	acceptor_loss	1.0000
17:48112573:GGA:G	acceptor_gain	1.0000
17:48112661:G:GG	donor_gain	1.0000
17:48113294:T:G	acceptor_gain	1.0000
17:48113298:T:G	acceptor_gain	1.0000
17:48113299:A:AG	acceptor_gain	1.0000
17:48113300:G:GG	acceptor_gain	1.0000
17:48113400:GT:G	donor_gain	1.0000
17:48113402:G:GG	donor_gain	1.0000
17:48118800:G:GG	donor_gain	1.0000
17:48107659:G:GT	donor_gain	0.9900
17:48112030:GAT:G	acceptor_gain	0.9900
17:48112572:A:AG	acceptor_gain	0.9900
17:48112572:AG:A	acceptor_gain	0.9900
17:48112572:AGGAG:A	acceptor_gain	0.9900
17:48112573:G:GG	acceptor_gain	0.9900
17:48112573:GG:G	acceptor_gain	0.9900
17:48112573:GGAGG:G	acceptor_gain	0.9900
17:48112657:CCAT:C	donor_gain	0.9900
17:48112658:CATG:C	donor_loss	0.9900
17:48112660:TGTGA:T	donor_loss	0.9900
17:48112661:GTG:G	donor_loss	0.9900
17:48112662:TGAG:T	donor_loss	0.9900
17:48112663:GA:G	donor_loss	0.9900
17:48112664:A:AT	donor_loss	0.9900
17:48112665:G:C	donor_loss	0.9900
17:48113284:T:G	acceptor_gain	0.9900
17:48113293:A:AG	acceptor_gain	0.9900

AlphaMissense

1745 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48112593:T:A	V21D	1.000
17:48112650:T:A	I40K	1.000
17:48112650:T:G	I40R	1.000
17:48113317:T:C	F49S	1.000
17:48113343:C:A	R58S	1.000
17:48112650:T:C	I40T	0.999
17:48113302:C:T	T44I	0.999
17:48113316:T:C	F49L	0.999
17:48113318:T:A	F49L	0.999
17:48113318:T:G	F49L	0.999
17:48113331:T:C	S54P	0.999
17:48113349:T:G	Y60D	0.999
17:48113358:T:C	F63L	0.999
17:48113359:T:C	F63S	0.999
17:48113360:C:A	F63L	0.999
17:48113360:C:G	F63L	0.999
17:48113380:T:C	L70P	0.999
17:48118781:T:C	L103P	0.999
17:48118789:T:C	F106L	0.999
17:48118791:C:A	F106L	0.999
17:48118791:C:G	F106L	0.999
17:48119014:C:G	H123D	0.999
17:48119020:T:C	F125L	0.999
17:48119021:T:C	F125S	0.999
17:48119022:C:A	F125L	0.999
17:48119022:C:G	F125L	0.999
17:48119029:A:C	S128R	0.999
17:48119031:C:A	S128R	0.999
17:48119031:C:G	S128R	0.999
17:48112643:T:G	Y38D	0.998

dbSNP variants (sampled 300 via entrez): RS1000191654 (17:48106707 C>T), RS1000226766 (17:48108243 GTTAC>G), RS1000324571 (17:48115917 T>TG), RS1000404740 (17:48112478 A>G), RS1000531645 (17:48107284 C>T), RS1000598475 (17:48108602 A>G,T), RS1000631334 (17:48106427 A>G), RS1000662923 (17:48115138 T>A), RS1000666505 (17:48114511 G>A), RS1000734749 (17:48114810 C>T), RS1000739571 (17:48114072 T>G), RS1000778392 (17:48121197 G>C,T), RS1000933376 (17:48107790 A>G), RS1000964620 (17:48106829 T>C), RS1001414140 (17:48115927 G>T)

Disease associations

OMIM: gene MIM:614906 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001662_4	Generalized epilepsy	9.000000e-09
GCST005951_17	Body mass index	3.000000e-09
GCST010173_156	Triglyceride levels	3.000000e-08
GCST010244_231	Triglyceride levels	2.000000e-18
GCST90000025_594	Appendicular lean mass	2.000000e-17

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Vincristine	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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