SNX17

Summary

SNX17 (sorting nexin 17, HGNC:14979) is a protein-coding gene on chromosome 2p23.3, encoding Sorting nexin-17 (Q15036). Critical regulator of endosomal recycling of numerous surface proteins, including integrins, signaling receptor and channels.

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, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9784 — RefSeq curated summary.

At a glance

• GWAS associations: 46
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_014748

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14979
Approved symbol	SNX17
Name	sorting nexin 17
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0064
Ensembl gene	ENSG00000115234
Ensembl biotype	protein_coding
OMIM	605963
Entrez	9784

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 20 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000233575, ENST00000427123, ENST00000440760, ENST00000453453, ENST00000464279, ENST00000484886, ENST00000489402, ENST00000493711, ENST00000494893, ENST00000537606, ENST00000901233, ENST00000901234, ENST00000901235, ENST00000901236, ENST00000901237, ENST00000901238, ENST00000901239, ENST00000901240, ENST00000901241, ENST00000901242, ENST00000901243, ENST00000901244, ENST00000917628, ENST00000917629, ENST00000917630, ENST00000917631, ENST00000971558, ENST00000971559

RefSeq mRNA: 4 — MANE Select: NM_014748 NM_001267059, NM_001267060, NM_001267061, NM_014748

CCDS: CCDS1750, CCDS58704

Canonical transcript exons

ENST00000233575 — 15 exons

Exon	Start	End
ENSE00000962997	27370616	27370806
ENSE00003476021	27374346	27374433
ENSE00003517589	27376606	27377535
ENSE00003527711	27375846	27375971
ENSE00003533996	27374085	27374175
ENSE00003541824	27371269	27371343
ENSE00003556896	27374689	27374758
ENSE00003573225	27372623	27372740
ENSE00003653420	27373861	27373971
ENSE00003655243	27376313	27376387
ENSE00003667653	27376479	27376520
ENSE00003669336	27373247	27373311
ENSE00003674210	27376106	27376183
ENSE00003690576	27375506	27375709
ENSE00003692961	27375061	27375153

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.9234 / max 271.3708, expressed in 1824 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19363	57.9234	1824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.57	gold quality
right adrenal gland	UBERON:0001233	97.03	gold quality
leukocyte	CL:0000738	96.97	gold quality
right adrenal gland cortex	UBERON:0035827	96.96	gold quality
monocyte	CL:0000576	96.95	gold quality
mononuclear cell	CL:0000842	96.93	gold quality
left adrenal gland	UBERON:0001234	96.67	gold quality
left adrenal gland cortex	UBERON:0035825	96.65	gold quality
adenohypophysis	UBERON:0002196	96.59	gold quality
stromal cell of endometrium	CL:0002255	96.47	gold quality
right coronary artery	UBERON:0001625	96.32	gold quality
spleen	UBERON:0002106	96.32	gold quality
right lobe of thyroid gland	UBERON:0001119	96.31	gold quality
apex of heart	UBERON:0002098	96.25	gold quality
adrenal cortex	UBERON:0001235	96.22	gold quality
left uterine tube	UBERON:0001303	96.21	gold quality
lower esophagus	UBERON:0013473	96.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.19	gold quality
pituitary gland	UBERON:0000007	96.13	gold quality
thoracic aorta	UBERON:0001515	96.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.07	gold quality
ascending aorta	UBERON:0001496	96.06	gold quality
mucosa of transverse colon	UBERON:0004991	96.06	gold quality
endocervix	UBERON:0000458	95.95	gold quality
metanephros cortex	UBERON:0010533	95.94	gold quality
adrenal gland	UBERON:0002369	95.92	gold quality
right uterine tube	UBERON:0001302	95.91	gold quality
right ovary	UBERON:0002118	95.90	gold quality
descending thoracic aorta	UBERON:0002345	95.85	gold quality
left lobe of thyroid gland	UBERON:0001120	95.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting SNX17, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
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-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-6749-3P	99.00	65.73	1443

Literature-anchored findings (GeneRIF, showing 13)

• expression level of SNX17 may regulate the lysosomal degradation, at least for P-selectin, by suppressing its entry into the inner vesicles of the multi-vesicular bodies (MVBs) (PMID:15769472)
• Snx 17 binds to a motif in the low-density lipoprotein (LDL) receptor-related protein (LRP) tail distinct from the endocytosis signals and promotes LRP sorting to the recycling pathway in the early endosomes. (PMID:16052210)
• SNX17 has a role in the indicated KRIT1 function in cell adhesion processes by integrin signaling (PMID:16712798)
• SNX17 regulates amyloid precursor protein trafficking and processing in the early endosomes (PMID:18276590)
• depletion of SNX17 in HeLa cells resulted in lysosomal degradation of multiple members of the integrin family of extracellular matrix recep-tors. (PMID:22492727)
• The authors demonstrate that SNX17 is essential for infection with all papillomavirus types analyzed, indicating an evolutionarily highly conserved virus entry mechanism. (PMID:23115288)
• Sorting nexin 17 regulates ApoER2 recycling and reelin signaling. (PMID:24705369)
• Data indicate that the major binding site for binding of sorting nexin 17 (SNX17) is confined to the NPXF2 motif in cytoplasmic adaptor protein Krev interaction trapped 1 (KRIT1). (PMID:25059659)
• SNX17 plays a role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse. (PMID:25825439)
• The double knockdown of SNX17 and SNX27 results in a striking reduction of papillomavirus 16 infection due to interruption of their binding to the L2 viral protein. (PMID:26202251)
• HPV-16 L2 recruitment of SNX17 occurs prior to capsid disassembly. (PMID:28475030)
• SNX17 Recruits USP9X to Antagonize MIB1-Mediated Ubiquitination and Degradation of PCM1 during Serum-Starvation-Induced Ciliogenesis. (PMID:31671755)
• Promotion of esophageal adenocarcinoma metastasis via Wnt/ss-catenin signal pathway by sorting nexins 3. (PMID:32187731)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx17	ENSDARG00000091418
mus_musculus	Snx17	ENSMUSG00000029146
rattus_norvegicus	Snx17	ENSRNOG00000026884
drosophila_melanogaster	Snx17	FBGN0032191
caenorhabditis_elegans		WBGENE00008927

Paralogs (2): SNX27 (ENSG00000143376), SNX31 (ENSG00000174226)

Protein

Protein identifiers

Sorting nexin-17 — Q15036 (reviewed: Q15036)

All UniProt accessions (5): B4DTB8, Q15036, F8WAZ0, F8WEG6, F8WFA0

UniProt curated annotations — full annotation on UniProt →

Function. Critical regulator of endosomal recycling of numerous surface proteins, including integrins, signaling receptor and channels. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Associates with retriever and CCC complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGB1, ITGB5 and their associated alpha subunits. Also required for maintenance of normal cell surface levels of APP and LRP1. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).

Subunit / interactions. Monomer. Interacts with APP (via cytoplasmic YXNPXY motif). Interacts with KIF1B. Interacts with the C-termini of P-selectin, PTC, LDLR, VLDLR, LRP1 and LRP8. Interacts with KRIT1 (via N-terminus). Interacts with HRAS. Interacts with ITGB1 and ITGB5 (via NPxY motif). Interacts with CCDC22 and CCDC93; the interaction associates SNX17 with the CCC complex. Interacts (via C-terminus) with VPS26C and VPS35L; the interactions are direct and associate SNX17 with the retriever complex.

Subcellular location. Cytoplasm. Early endosome. Cytoplasmic vesicle membrane.

Domain organisation. The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)). Required for association with endosomes. The PTB-like F3 module within the FERM-like domain mediates cargo recognition via their NPxY sequences, while the F1 module (Ras-associating) is responsible for interaction with membrane-bound HRAS.

Similarity. Belongs to the sorting nexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15036-1	1	yes
Q15036-2	2

RefSeq proteins (4): NP_001253988, NP_001253989, NP_001253990, NP_055563* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR001683	PX_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR028666	SNX17_FERM_N	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037836	SNX17_FERM-like_dom	Domain
IPR040842	SNX17/31_FERM	Domain
IPR048763	SNX17-31_FERM_F1	Domain
IPR048767	SNX17-31_FERM_F2	Domain

Pfam: PF00787, PF18116, PF21271, PF21273

UniProt features (64 total): strand 17, helix 14, mutagenesis site 9, modified residue 7, binding site 4, region of interest 4, turn 4, domain 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3LUI	X-RAY DIFFRACTION	1.8
4GXB	X-RAY DIFFRACTION	1.8
3FOG	X-RAY DIFFRACTION	2.8
4TKN	X-RAY DIFFRACTION	3
9AU7	ELECTRON MICROSCOPY	3.4
7RM8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15036-F1	83.38	0.69

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): 75; 36; 38; 62

Post-translational modifications (7): 336, 407, 409, 415, 421, 437, 440

Mutagenesis-validated functional residues (9):

Position	Phenotype
62	no association with endosomes.
432	no effect on interaction with ccdc22, ccdc93, vps26c and vps35l.
433	no effect on interaction with ccdc22, ccdc93, vps26c and vps35l.
440	no effect on interaction with ccdc22, ccdc93, vps26c and vps35l.
464	slightly decreases interaction with ccdc22, ccdc93, vps26c and vps35l.
467–470	strongly decreases interaction with ccdc22, ccdc93, vps26c and vps35l. no effect on endosomal location.
469	slightly decreases interaction with ccdc22, ccdc93, vps26c and vps35l.
470	strongly decreases interaction with ccdc22, ccdc93, vps26c and vps35l. no effect on endosomal location.
470	abolishes interaction with the retriever complex.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 186 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ARTERY_DEVELOPMENT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_AORTA_DEVELOPMENT, TCF4_Q5, MARTINEZ_RB1_TARGETS_DN, TGACATY_UNKNOWN, GOBP_LIPID_METABOLIC_PROCESS, GATA1_03, GOBP_REGULATION_OF_ENDOCYTOSIS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (13): kidney development (GO:0001822), cardiac septum development (GO:0003279), cholesterol catabolic process (GO:0006707), intracellular protein transport (GO:0006886), receptor-mediated endocytosis (GO:0006898), signal transduction (GO:0007165), endosomal transport (GO:0016197), regulation of endocytosis (GO:0030100), endocytic recycling (GO:0032456), aorta development (GO:0035904), coronary vasculature development (GO:0060976), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (5): signaling receptor binding (GO:0005102), phosphatidylinositol binding (GO:0035091), low-density lipoprotein particle receptor binding (GO:0050750), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): endosome (GO:0005768), early endosome (GO:0005769), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endosome membrane (GO:0010008), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), cytoplasmic vesicle membrane (GO:0030659)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
intracellular protein localization	2
intracellular transport	2
endocytosis	2
cellular process	2
transport	2
binding	2
endomembrane system	2
cytoplasmic vesicle	2
endosome	2
animal organ development	1
renal system development	1
cardiac chamber development	1
anatomical structure development	1
cholesterol metabolic process	1
sterol catabolic process	1
alcohol catabolic process	1
protein transport	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
vesicle-mediated transport	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
artery development	1
blood vessel development	1
heart development	1
establishment of protein localization	1
protein binding	1
anion binding	1
lipoprotein particle receptor binding	1
intracellular membrane-bounded organelle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
intracellular vesicle	1
cellular_component	1

Protein interactions and networks

STRING

1402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX17	KRIT1	O00522	967
SNX17	SELP	P16109	957
SNX17	SNX1	Q13596	909
SNX17	VPS35	Q96QK1	820
SNX17	LRP8	Q14114	808
SNX17	SNX2	P82862	802
SNX17	VPS35L	Q7Z3J2	798
SNX17	SNX5	Q9Y5X3	794
SNX17	SERPINE2	P07093	785
SNX17	SNX3	O60493	758
SNX17	CCDC93	Q567U6	757
SNX17	VPS26C	O14972	756
SNX17	STAB1	Q9NY15	744
SNX17	VPS29	Q9UBQ0	744
SNX17	SNX12	Q9UMY4	726

IntAct

109 interactions, top by confidence:

A	B	Type	Score
HOXC8	SNX17	psi-mi:“MI:0915”(physical association)	0.670
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
RIN1	SNX17	psi-mi:“MI:0915”(physical association)	0.560
SNX17	RABAC1	psi-mi:“MI:0915”(physical association)	0.560
SNX17	RNF128	psi-mi:“MI:0915”(physical association)	0.560
APP	SNX17	psi-mi:“MI:0915”(physical association)	0.560
PLCG1	SNX17	psi-mi:“MI:0407”(direct interaction)	0.540
SNX17	PLCG1	psi-mi:“MI:0915”(physical association)	0.540
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
NCR3LG1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
IL20RA	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
RHEX	NOS1AP	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
GMPR2	GMPR	psi-mi:“MI:0914”(association)	0.500
SNX17		psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (139): SNX17 (Affinity Capture-RNA), SNX17 (Affinity Capture-RNA), SELP (Co-crystal Structure), SNX17 (Reconstituted Complex), INSR (Affinity Capture-Western), NTRK1 (Affinity Capture-Western), HRAS (Reconstituted Complex), SELP (Protein-peptide), APP (Protein-peptide), SNX17 (Affinity Capture-MS), SNX17 (Affinity Capture-MS), SNX17 (Affinity Capture-MS), SNX17 (Affinity Capture-MS), SNX17 (Affinity Capture-MS), SELP (Two-hybrid)

ESM2 similar proteins: A0JN62, A2RT67, A2VDU2, A4IIM3, B4F779, F1Q8X5, O94967, P48553, P59113, Q0VEJ0, Q15036, Q28C34, Q32LP0, Q3B7D5, Q3TLI0, Q3UVG3, Q5R4A5, Q5R8M5, Q5RCP7, Q5RDV5, Q5RID7, Q658Y4, Q6AYF1, Q6AYS6, Q6DRP4, Q6NRD0, Q6PCS4, Q6QD73, Q7TSG1, Q7ZYD9, Q7ZYH1, Q8BIK4, Q8BKH7, Q8BVL3, Q8CGF6, Q8CIB5, Q8K1B8, Q8K2Y9, Q8K3G9, Q8N6S4

Diamond homologs: Q15036, Q28HD5, Q5EA77, Q5R4A5, Q5RID7, Q6AYS6, Q6DDY6, Q6P8Y7, Q8BVL3, Q8N9S9, A5DHC9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 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
Downstream signal transduction	9	43.9×	1e-10
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	39.9×	2e-06
Regulation of signaling by CBL	5	31.8×	4e-05
Nephrin family interactions	5	30.5×	4e-05
DAP12 signaling	6	28.3×	7e-06
Signaling by SCF-KIT	7	22.3×	4e-06
Signaling by FGFR1 in disease	5	18.8×	3e-04
RHOU GTPase cycle	5	17.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
extrinsic apoptotic signaling pathway via death domain receptors	6	23.6×	2e-04
ephrin receptor signaling pathway	5	16.9×	5e-03
intrinsic apoptotic signaling pathway in response to DNA damage	5	15.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2043 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27370804:GTG:G	donor_gain	1.0000
2:27372621:A:AG	acceptor_gain	1.0000
2:27372622:G:GG	acceptor_gain	1.0000
2:27372737:GCTG:G	donor_gain	1.0000
2:27372755:GAAAC:G	donor_gain	1.0000
2:27373244:TAGTT:T	acceptor_loss	1.0000
2:27373245:A:AG	acceptor_gain	1.0000
2:27373245:AGTTC:A	acceptor_gain	1.0000
2:27373246:G:GA	acceptor_gain	1.0000
2:27373246:GT:G	acceptor_gain	1.0000
2:27373246:GTT:G	acceptor_gain	1.0000
2:27373246:GTTC:G	acceptor_gain	1.0000
2:27373246:GTTCG:G	acceptor_gain	1.0000
2:27373307:AACAG:A	donor_loss	1.0000
2:27373309:CAGGT:C	donor_loss	1.0000
2:27373310:AG:A	donor_loss	1.0000
2:27373311:GG:G	donor_loss	1.0000
2:27373312:GT:G	donor_loss	1.0000
2:27373313:T:A	donor_loss	1.0000
2:27373960:G:GT	donor_gain	1.0000
2:27373969:G:GT	donor_gain	1.0000
2:27373970:AGGT:A	donor_loss	1.0000
2:27373972:G:A	donor_loss	1.0000
2:27373973:T:G	donor_loss	1.0000
2:27374080:CCCA:C	acceptor_loss	1.0000
2:27374082:CAGG:C	acceptor_loss	1.0000
2:27374084:GGCT:G	acceptor_gain	1.0000
2:27374160:G:GT	donor_gain	1.0000
2:27374176:G:GG	donor_gain	1.0000
2:27374337:A:AG	acceptor_gain	1.0000

AlphaMissense

3058 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27371272:T:G	Y23D	1.000
2:27371279:T:A	I25N	1.000
2:27371289:T:A	N28K	1.000
2:27371289:T:G	N28K	1.000
2:27371304:T:G	C33W	1.000
2:27371314:T:C	Y37H	1.000
2:27371314:T:G	Y37D	1.000
2:27371315:A:G	Y37C	1.000
2:27371324:T:C	L40P	1.000
2:27372660:T:C	F59S	1.000
2:27372670:G:C	K62N	1.000
2:27372670:G:T	K62N	1.000
2:27372708:G:C	R75T	1.000
2:27372708:G:T	R75M	1.000
2:27372709:G:C	R75S	1.000
2:27372709:G:T	R75S	1.000
2:27372711:G:C	R76T	1.000
2:27372711:G:T	R76I	1.000
2:27372712:A:C	R76S	1.000
2:27372712:A:T	R76S	1.000
2:27372720:T:C	L79S	1.000
2:27372728:T:G	Y82D	1.000
2:27373295:T:C	L102P	1.000
2:27373303:G:C	A105P	1.000
2:27374366:T:C	F182L	1.000
2:27374368:T:A	F182L	1.000
2:27374368:T:G	F182L	1.000
2:27374376:C:A	P185H	1.000
2:27374376:C:G	P185R	1.000
2:27374735:G:C	G220R	1.000

dbSNP variants (sampled 300 via entrez): RS1000261636 (2:27371663 C>T), RS1001291963 (2:27371154 C>A,T), RS1001299104 (2:27370820 G>T), RS1001764216 (2:27371415 A>T), RS1002297713 (2:27370329 G>A,C), RS1002364984 (2:27370517 G>A,C), RS1002593768 (2:27372209 T>C), RS1003299688 (2:27369094 G>A), RS1003346734 (2:27376292 G>A), RS1003373283 (2:27369442 G>A), RS1003395315 (2:27375928 T>C), RS1003695472 (2:27370969 G>A), RS1004256632 (2:27372222 C>G,T), RS1004503387 (2:27377381 C>G,T), RS1004598666 (2:27376150 G>A)

Disease associations

OMIM: gene MIM:605963 | disease phenotypes: MIM:268000

GenCC curated gene-disease

Mondo (1): retinitis pigmentosa (MONDO:0019200)

Orphanet (1): Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

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

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST004131_72	Inflammatory bowel disease	1.000000e-07
GCST004132_64	Crohn’s disease	6.000000e-11
GCST004611_9	High light scatter reticulocyte count	1.000000e-18
GCST004619_117	Reticulocyte fraction of red cells	2.000000e-26
GCST004622_150	Reticulocyte count	4.000000e-20
GCST006463_2	Urinary albumin excretion (no hypertensive medication)	8.000000e-10
GCST006586_2	Urinary albumin excretion	7.000000e-12
GCST006716_1	Alcohol use disorder (total score)	9.000000e-13
GCST007717_1	Urinary sodium to potassium ratio	1.000000e-17
GCST007718_10	Urinary albumin-to-creatinine ratio	4.000000e-08
GCST008074_17	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-29
GCST008074_25	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-200
GCST008074_63	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-09
GCST008074_70	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-75
GCST008074_92	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-237
GCST008076_10	Triglyceride levels	1.000000e-15
GCST008076_17	Triglyceride levels	2.000000e-138
GCST008076_53	Triglyceride levels	2.000000e-72
GCST008076_83	Triglyceride levels	1.000000e-54
GCST008078_101	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-15
GCST008078_17	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-12
GCST008079_148	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-18
GCST008079_20	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-14
GCST008083_136	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-247
GCST008083_36	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	9.000000e-29
GCST008083_44	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	9.000000e-203
GCST008083_59	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-07
GCST008083_62	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-75
GCST008086_1	LDL cholesterol levels in current drinkers	8.000000e-08
GCST008086_32	LDL cholesterol levels in current drinkers	2.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004285	albuminuria
EFO:0009458	alcohol use disorder measurement
EFO:0009884	urinary sodium to potassium ratio
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0008111	diet measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
tetrabromobisphenol A	decreases expression	1
periodate-oxidized adenosine	affects expression	1
coumarin	increases phosphorylation	1
arsenic disulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Caffeine	decreases phosphorylation	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2GY	Abcam HeLa SNX17 KO	Cancer cell line	Female
CVCL_TP87	HAP1 SNX17 (-) 1	Cancer cell line	Male
CVCL_TP88	HAP1 SNX17 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa