SNX25

Summary

SNX25 (sorting nexin 25, HGNC:21883) is a protein-coding gene on chromosome 4q35.1, encoding Sorting nexin-25 (Q9H3E2). May be involved in several stages of intracellular trafficking.

Predicted to enable phosphatidylinositol binding activity and type I transforming growth factor beta receptor binding activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway and receptor catabolic process. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 83891 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 110 total
• MANE Select transcript: NM_001378034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21883
Approved symbol	SNX25
Name	sorting nexin 25
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	SBBI31
Ensembl gene	ENSG00000109762
Ensembl biotype	protein_coding
OMIM	620961
Entrez	83891

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 20 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000264694, ENST00000504273, ENST00000504959, ENST00000506896, ENST00000512853, ENST00000513433, ENST00000514884, ENST00000618785, ENST00000652585, ENST00000850971, ENST00000862627, ENST00000862628, ENST00000862629, ENST00000927308, ENST00000927309, ENST00000927310, ENST00000927311, ENST00000927312, ENST00000927313, ENST00000927314, ENST00000968206, ENST00000968207, ENST00000968208, ENST00000968209, ENST00000968210, ENST00000968211

RefSeq mRNA: 7 — MANE Select: NM_001378034 NM_001317781, NM_001378032, NM_001378034, NM_001378035, NM_001378036, NM_001378037, NM_001423234

CCDS: CCDS34116, CCDS93675

Canonical transcript exons

ENST00000652585 — 19 exons

Exon	Start	End
ENSE00002027525	185363385	185363966
ENSE00002289965	185288012	185288082
ENSE00002305978	185264438	185264610
ENSE00002319934	185266969	185267155
ENSE00003465824	185353485	185353602
ENSE00003476590	185361924	185362105
ENSE00003483681	185346537	185346650
ENSE00003484511	185332595	185332759
ENSE00003488299	185323528	185323800
ENSE00003538989	185258848	185259064
ENSE00003556982	185362611	185362711
ENSE00003588064	185320733	185320864
ENSE00003597238	185310635	185310816
ENSE00003656607	185357671	185357737
ENSE00003673792	185351445	185351609
ENSE00003682726	185339379	185339510
ENSE00003682765	185341976	185342116
ENSE00003842346	185247294	185247378
ENSE00003849209	185209598	185210255

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 95.07.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.07	gold quality
secondary oocyte	CL:0000655	94.14	gold quality
lower lobe of lung	UBERON:0008949	93.43	gold quality
pigmented layer of retina	UBERON:0001782	93.27	gold quality
decidua	UBERON:0002450	91.07	gold quality
lung	UBERON:0002048	88.93	gold quality
epithelial cell of pancreas	CL:0000083	88.65	silver quality
upper lobe of lung	UBERON:0008948	88.55	gold quality
upper lobe of left lung	UBERON:0008952	88.13	gold quality
cerebellar cortex	UBERON:0002129	87.25	gold quality
cerebellar hemisphere	UBERON:0002245	87.24	gold quality
calcaneal tendon	UBERON:0003701	87.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.04	gold quality
cerebellum	UBERON:0002037	86.94	gold quality
right lung	UBERON:0002167	86.79	gold quality
descending thoracic aorta	UBERON:0002345	86.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.37	gold quality
ascending aorta	UBERON:0001496	86.32	gold quality
thoracic aorta	UBERON:0001515	86.25	gold quality
substantia nigra pars compacta	UBERON:0001965	86.25	gold quality
visceral pleura	UBERON:0002401	85.63	gold quality
tendon	UBERON:0000043	85.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.45	gold quality
islet of Langerhans	UBERON:0000006	85.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.36	gold quality
epithelium of nasopharynx	UBERON:0001951	85.27	gold quality
nasopharynx	UBERON:0001728	85.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.86	gold quality
pons	UBERON:0000988	84.85	gold quality
aorta	UBERON:0000947	84.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• SNX25 negatively regulates TGF-beta signaling by enhancing the receptor degradation through lysosome pathway. (PMID:21266196)
• upregulation of SNX25 might be involved in the development of temporal lobe epilepsy. (PMID:23518199)
• This study confirmed that SNX25 as genetic modifiers of age at onset of Alzheimer disease. (PMID:26214276)
• RP11-714G18.1 may play an athero-protective role by inhibiting vascular cell migration via RP11-714G18.1/LRP2BP/MMP1 signaling pathway. (PMID:29363163)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx25	ENSDARG00000099545
mus_musculus	Snx25	ENSMUSG00000038291
rattus_norvegicus	Snx25	ENSRNOG00000011116
drosophila_melanogaster	snz	FBGN0029976

Paralogs (3): SNX13 (ENSG00000071189), SNX19 (ENSG00000120451), SNX14 (ENSG00000135317)

Protein

Protein identifiers

Sorting nexin-25 — Q9H3E2 (reviewed: Q9H3E2)

All UniProt accessions (3): Q9H3E2, A0A494C0S0, H0Y9R5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in several stages of intracellular trafficking.

Subcellular location. Endosome membrane.

Similarity. Belongs to the sorting nexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H3E2-1	1	yes
Q9H3E2-2	2

RefSeq proteins (7): NP_001304710, NP_001364961, NP_001364963, NP_001364964, NP_001364965, NP_001364966, NP_001410163 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR003114	Phox_assoc	Domain
IPR013937	Sorting_nexin_C	Domain
IPR016137	RGS	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037899	SNX25_PX	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615, PF00787, PF02194, PF08628

UniProt features (30 total): helix 14, strand 4, domain 3, sequence variant 3, splice variant 2, chain 1, turn 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7SR1	X-RAY DIFFRACTION	2.4
7SR2	X-RAY DIFFRACTION	2.42
5WOE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3E2-F1	76.12	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 665

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 123 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, AAGCAAT_MIR137, HNF3ALPHA_Q6, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ATGTTAA_MIR302C, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, chr4q35, CORRE_MULTIPLE_MYELOMA_UP, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_TRANSFORMING_GROWTH_FACTOR_BETA_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (3): protein transport (GO:0015031), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), receptor catabolic process (GO:0032801)

GO Molecular Function (2): phosphatidylinositol binding (GO:0035091), type I transforming growth factor beta receptor binding (GO:0034713)

GO Cellular Component (3): endosome (GO:0005768), endosome membrane (GO:0010008), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
macromolecule catabolic process	1
receptor metabolic process	1
anion binding	1
transforming growth factor beta receptor binding	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX25	RNMT	O43148	766
SNX25	SAXO6	Q8TC05	614
SNX25	SNX27	Q96L92	578
SNX25	SNX14	Q9Y5W7	532
SNX25	SNX15	Q9NRS6	532
SNX25	SNX17	Q15036	531
SNX25	SNX2	P82862	507
SNX25	SNX3	O60493	499
SNX25	SNX1	Q13596	496
SNX25	SNX20	Q7Z614	476
SNX25	ANKRD10	Q9NXR5	472
SNX25	SNX5	Q9Y5X3	465
SNX25	SNX6	Q9UNH7	465
SNX25	SNX11	Q9Y5W9	460
SNX25	RGS21	Q2M5E4	456

IntAct

60 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
NDUFC2	NDUFS4	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
SLC30A4	OPA1	psi-mi:“MI:0914”(association)	0.530
ATP6V0D1		psi-mi:“MI:0914”(association)	0.350
TSPAN5	KLHL2	psi-mi:“MI:0914”(association)	0.350
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
GJA8	STX7	psi-mi:“MI:0914”(association)	0.350
COA3	COX5B	psi-mi:“MI:0914”(association)	0.350
GJA3	GJB3	psi-mi:“MI:0914”(association)	0.350
APH1A	SNX19	psi-mi:“MI:0914”(association)	0.350
SLC15A2	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC1A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC2A8	AP3D1	psi-mi:“MI:0914”(association)	0.350
SLC30A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC35C2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SLC35F1	C15orf61	psi-mi:“MI:0914”(association)	0.350
SLC35F3	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC39A1	CPD	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-RNA), SNX25 (Proximity Label-MS), SNX25 (Proximity Label-MS), SNX25 (Proximity Label-MS), SNX25 (Affinity Capture-RNA), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS), SNX25 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L0, A6H6A9, B4F779, G5E8V9, O35382, O60890, O95219, P0CAX5, P53365, P53367, Q08DP6, Q28E02, Q3ZCL5, Q4V7P7, Q566W7, Q5EAD0, Q5R4C2, Q5RCW6, Q5T0N5, Q5VWJ9, Q5ZJ17, Q60437, Q62824, Q6AY65, Q6GMN2, Q6PCS4, Q6Y5D8, Q6ZQ82, Q7YQL5, Q7YQL6, Q80TY0, Q8BHY8, Q8BKX1, Q8CE50, Q8K221, Q8K3G9, Q8K3H0, Q8N6S4, Q8NEU8, Q8R511

Diamond homologs: Q3ZT31, Q9H3E2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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
R-HSA-425366	8	30.2×	8e-08
SLC-mediated transmembrane transport	9	11.1×	2e-05
Transport of small molecules	10	5.2×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	6	31.2×	3e-05
transport across blood-brain barrier	5	14.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5040 predictions. Top by Δscore:

Variant	Effect	Δscore
4:185247288:T:G	acceptor_gain	1.0000
4:185247288:TTTCA:T	acceptor_loss	1.0000
4:185247289:TTCA:T	acceptor_loss	1.0000
4:185247290:TCA:T	acceptor_loss	1.0000
4:185247291:CAGAG:C	acceptor_loss	1.0000
4:185247292:A:AG	acceptor_gain	1.0000
4:185247292:A:T	acceptor_loss	1.0000
4:185247293:G:A	acceptor_loss	1.0000
4:185247293:G:GA	acceptor_gain	1.0000
4:185247293:GA:G	acceptor_gain	1.0000
4:185258842:T:TA	acceptor_gain	1.0000
4:185264423:A:AG	acceptor_gain	1.0000
4:185264499:G:GG	donor_gain	1.0000
4:185266967:A:AG	acceptor_gain	1.0000
4:185266968:G:GT	acceptor_gain	1.0000
4:185266968:GT:G	acceptor_gain	1.0000
4:185266968:GTC:G	acceptor_gain	1.0000
4:185266968:GTCT:G	acceptor_gain	1.0000
4:185266968:GTCTT:G	acceptor_gain	1.0000
4:185267151:CTAAG:C	donor_loss	1.0000
4:185267152:TAAG:T	donor_loss	1.0000
4:185267153:AAG:A	donor_loss	1.0000
4:185267154:AGGTA:A	donor_loss	1.0000
4:185267155:GGTA:G	donor_loss	1.0000
4:185267156:G:GA	donor_loss	1.0000
4:185267157:T:A	donor_loss	1.0000
4:185288003:A:AG	acceptor_gain	1.0000
4:185288004:A:G	acceptor_gain	1.0000
4:185310775:G:GT	donor_gain	1.0000
4:185310812:AGAAG:A	donor_loss	1.0000

AlphaMissense

6643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:185310704:T:C	L247P	1.000
4:185339484:T:A	W510R	1.000
4:185339484:T:C	W510R	1.000
4:185288040:G:C	A210P	0.999
4:185310712:G:C	A250P	0.999
4:185339463:T:A	W503R	0.999
4:185339463:T:C	W503R	0.999
4:185342016:T:A	V532D	0.999
4:185342060:T:A	W547R	0.999
4:185342060:T:C	W547R	0.999
4:185342067:T:A	V549D	0.999
4:185342074:A:C	R551S	0.999
4:185342074:A:T	R551S	0.999
4:185342088:T:C	F556S	0.999
4:185342109:T:C	L563P	0.999
4:185351497:T:C	L621S	0.999
4:185339434:T:C	L493P	0.998
4:185339465:G:C	W503C	0.998
4:185339465:G:T	W503C	0.998
4:185339486:G:C	W510C	0.998
4:185339486:G:T	W510C	0.998
4:185339491:C:A	A512D	0.998
4:185346565:T:C	L575S	0.998
4:185346621:T:C	S594P	0.998
4:185346634:T:C	L598S	0.998
4:185351485:T:C	L617P	0.998
4:185351493:T:C	F620L	0.998
4:185351494:T:C	F620S	0.998
4:185351495:C:A	F620L	0.998
4:185351495:C:G	F620L	0.998

dbSNP variants (sampled 300 via entrez): RS1000029578 (4:185288610 G>A), RS10000719 (4:185321079 T>C), RS10000918 (4:185347422 A>G,T), RS1000196546 (4:185311719 G>A,T), RS1000199165 (4:185266488 G>A), RS1000226004 (4:185312114 C>A,T), RS1000230002 (4:185354945 G>A,T), RS1000242747 (4:185294093 GAT>G), RS1000262850 (4:185337024 G>A), RS1000332702 (4:185306797 C>T), RS1000356913 (4:185349552 T>C), RS1000401598 (4:185348982 T>G), RS1000411012 (4:185257883 T>C), RS1000417232 (4:185343063 G>A), RS1000431006 (4:185263855 A>T)

Disease associations

OMIM: gene MIM:620961 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	6
trichostatin A	affects expression, affects cotreatment, decreases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
8-Hydroxy-2’-Deoxyguanosine	affects abundance, affects response to substance, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cadmium	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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