SNX12

Summary

SNX12 (sorting nexin 12, HGNC:14976) is a protein-coding gene on chromosome Xq13.1, encoding Sorting nexin-12 (Q9UMY4). 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. This protein does not contain a coiled coil region, like some family members. A similar protein in mouse may be involved in regulating the neurite outgrowth. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 29934 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_013346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14976
Approved symbol	SNX12
Name	sorting nexin 12
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147164
Ensembl biotype	protein_coding
OMIM	300883
Entrez	29934

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000276105, ENST00000374274, ENST00000465030, ENST00000483560, ENST00000490561, ENST00000622259, ENST00000622277, ENST00000915458

RefSeq mRNA: 5 — MANE Select: NM_013346 NM_001256185, NM_001256186, NM_001256187, NM_001256188, NM_013346

CCDS: CCDS14405, CCDS59169

Canonical transcript exons

ENST00000374274 — 4 exons

Exon	Start	End
ENSE00001463000	71059247	71061118
ENSE00001844920	71068142	71068334
ENSE00003578348	71062854	71062949
ENSE00003586794	71061843	71061967

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.3233 / max 165.9154, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199538	16.8543	1809
199539	10.7167	1799
199537	0.5449	311
199540	0.2074	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	95.46	gold quality
cortical plate	UBERON:0005343	95.36	gold quality
islet of Langerhans	UBERON:0000006	95.31	gold quality
smooth muscle tissue	UBERON:0001135	94.26	gold quality
adrenal tissue	UBERON:0018303	93.79	gold quality
embryo	UBERON:0000922	93.43	gold quality
ganglionic eminence	UBERON:0004023	93.43	gold quality
lower esophagus mucosa	UBERON:0035834	93.23	gold quality
right adrenal gland	UBERON:0001233	93.19	gold quality
right adrenal gland cortex	UBERON:0035827	93.18	gold quality
prefrontal cortex	UBERON:0000451	93.17	gold quality
left adrenal gland	UBERON:0001234	93.14	gold quality
left adrenal gland cortex	UBERON:0035825	92.99	gold quality
esophagus mucosa	UBERON:0002469	92.90	gold quality
stromal cell of endometrium	CL:0002255	92.83	gold quality
rectum	UBERON:0001052	92.81	gold quality
popliteal artery	UBERON:0002250	92.79	gold quality
tibial artery	UBERON:0007610	92.78	gold quality
descending thoracic aorta	UBERON:0002345	92.74	gold quality
adrenal gland	UBERON:0002369	92.64	gold quality
artery	UBERON:0001637	92.56	gold quality
esophagus squamous epithelium	UBERON:0006920	92.53	gold quality
aorta	UBERON:0000947	92.52	gold quality
ectocervix	UBERON:0012249	92.52	gold quality
oocyte	CL:0000023	92.49	gold quality
body of uterus	UBERON:0009853	92.48	gold quality
gall bladder	UBERON:0002110	92.47	gold quality
left coronary artery	UBERON:0001626	92.37	gold quality
adrenal cortex	UBERON:0001235	92.36	gold quality
hypothalamus	UBERON:0001898	92.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	85.07
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting SNX12, 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-4533	100.00	69.48	2758
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
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-6739-5P	99.80	67.87	2806
HSA-MIR-6817-3P	99.79	68.35	2126

Literature-anchored findings (GeneRIF, showing 4)

• Metallothionein deficient mice have a marked decrease in Snx12 during acute lung injury (PMID:16166738)
• SNX12 protein level is dramatically decreased in the brain of Alzheimer’s disease patients as compared to that of controls. (PMID:22709416)
• find that overexpression of SNX12 restores the sorting process in an Hrs knockdown background. Altogether, our data show that despite lower expression level, SNX12 shares redundant functions with SNX3 in the biogenesis of multivesicular endosomes (PMID:22719997)
• SNX12 plays a key role in intraluminal vesicle formation and in the maturation of a subpopulation of early endosomes into late endosomes, thereby regulating selective endocytic transport of cargo for degradation. (PMID:28705836)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx12	ENSDARG00000019060
mus_musculus	Snx12	ENSMUSG00000046032
rattus_norvegicus	Snx12	ENSRNOG00000004036
drosophila_melanogaster	Snx3	FBGN0038065
caenorhabditis_elegans	snx-3	WBGENE00006503

Paralogs (15): SNX11 (ENSG00000002919), SNX1 (ENSG00000028528), SNX10 (ENSG00000086300), SNX5 (ENSG00000089006), SNX8 (ENSG00000106266), SNX3 (ENSG00000112335), SNX4 (ENSG00000114520), SNX6 (ENSG00000129515), SNX9 (ENSG00000130340), SNX30 (ENSG00000148158), SNX7 (ENSG00000162627), SNX32 (ENSG00000172803), SNX33 (ENSG00000173548), SNX18 (ENSG00000178996), SNX2 (ENSG00000205302)

Protein

Protein identifiers

Sorting nexin-12 — Q9UMY4 (reviewed: Q9UMY4)

All UniProt accessions (3): Q9UMY4, A0A087X0R6, Q3SYF1

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Membrane.

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

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the sorting nexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UMY4-2	2	yes
Q9UMY4-1	1
Q9UMY4-3	3

RefSeq proteins (5): NP_001243114, NP_001243115, NP_001243116, NP_001243117, NP_037478* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR051074	Sorting_Nexin	Family

Pfam: PF00787

UniProt features (23 total): strand 5, helix 4, binding site 4, modified residue 3, splice variant 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CSK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMY4-F1	91.08	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): 71; 73; 96; 119

Post-translational modifications (3): 73, 2, 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 225 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_MATURATION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_CATABOLIC_PROCESS, OCT1_03, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_REGULATION_OF_EARLY_ENDOSOME_TO_LATE_ENDOSOME_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION

GO Biological Process (9): negative regulation of gene expression (GO:0010629), negative regulation of protein processing (GO:0010955), protein transport (GO:0015031), regulation of endocytosis (GO:0030100), endocytic recycling (GO:0032456), late endosome to Golgi transport (GO:0034499), negative regulation of protein catabolic process (GO:0042177), negative regulation of protein transport (GO:0051224), negative regulation of early endosome to late endosome transport (GO:2000642)

GO Molecular Function (5): enzyme binding (GO:0019899), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (4): early endosome (GO:0005769), retromer complex (GO:0030904), early endosome membrane (GO:0031901), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
protein processing	1
negative regulation of proteolysis	1
regulation of protein processing	1
negative regulation of protein maturation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
cytoplasm	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
protein transport	1
negative regulation of transport	1
regulation of protein transport	1
negative regulation of protein localization	1
negative regulation of establishment of protein localization	1
negative regulation of intracellular transport	1
early endosome to late endosome transport	1
regulation of early endosome to late endosome transport	1
protein binding	1
phosphatidylinositol phosphate binding	1
anion binding	1
endosome	1
endomembrane system	1
membrane protein complex	1
early endosome	1
endosome membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX12	SNX5	Q9Y5X3	781
SNX12	SNX27	Q96L92	777
SNX12	SNX6	Q9UNH7	774
SNX12	SNX17	Q15036	726
SNX12	SNX33	Q8WV41	638
SNX12	SNX4	O95219	610
SNX12	SNX8	Q9Y5X2	607
SNX12	SNX22	Q96L94	603
SNX12	SNX15	Q9NRS6	601
SNX12	VPS35	Q96QK1	592
SNX12	SNX2	P82862	592
SNX12	SNX1	Q13596	587
SNX12	VPS29	Q9UBQ0	574
SNX12	VPS26A	O75436	553
SNX12	SNX32	Q86XE0	536

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.670
ARL6IP1	SNX12	psi-mi:“MI:0915”(physical association)	0.560
SNX12	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
AGT	SNX12	psi-mi:“MI:0915”(physical association)	0.560
SNX12	KLKB1	psi-mi:“MI:0915”(physical association)	0.560
SNX12	LPL	psi-mi:“MI:0915”(physical association)	0.560
SNX12	CCT2	psi-mi:“MI:0915”(physical association)	0.560
CCT8	SNX12	psi-mi:“MI:0915”(physical association)	0.560
SNX12	PACSIN1	psi-mi:“MI:0915”(physical association)	0.560
HTT	SNX12	psi-mi:“MI:0915”(physical association)	0.560
SNX3	VPS26A	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
CDC42EP4	SEPTIN6	psi-mi:“MI:0914”(association)	0.530

BioGRID (59): SNX12 (Two-hybrid), AKR1A1 (Co-fractionation), GNPDA2 (Co-fractionation), PIN1 (Co-fractionation), PPIL3 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation), SNX12 (Co-fractionation)

ESM2 similar proteins: D3ZRP6, D4A055, F1QH17, O22715, O60493, O70492, O70493, O95619, P0CR61, P48454, P48455, Q0G819, Q15691, Q1RMH8, Q1RMS5, Q27889, Q28E02, Q2U4K2, Q3SYW1, Q3ZBD9, Q4I1H6, Q4WWS3, Q5R5V1, Q5R752, Q5R7Z5, Q5U211, Q5XH73, Q5ZKU1, Q5ZLC7, Q60EW9, Q61166, Q66HR2, Q66T82, Q68FK8, Q6AXU9, Q6C2S9, Q6IR85, Q6P848, Q6V291, Q76EZ2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

595 predictions. Top by Δscore:

Variant	Effect	Δscore
X:71061114:CAATT:C	acceptor_gain	1.0000
X:71061117:TT:T	acceptor_gain	1.0000
X:71061119:C:CC	acceptor_gain	1.0000
X:71061838:CTTA:C	donor_loss	1.0000
X:71061839:TTACT:T	donor_loss	1.0000
X:71061840:TACTT:T	donor_loss	1.0000
X:71061841:A:AC	donor_gain	1.0000
X:71061841:ACTTG:A	donor_loss	1.0000
X:71061842:C:CG	donor_gain	1.0000
X:71061842:CT:C	donor_gain	1.0000
X:71061842:CTT:C	donor_gain	1.0000
X:71061842:CTTG:C	donor_gain	1.0000
X:71061871:T:TA	donor_gain	1.0000
X:71061964:CAAT:C	acceptor_gain	1.0000
X:71061965:AATC:A	acceptor_loss	1.0000
X:71061966:AT:A	acceptor_gain	1.0000
X:71061968:C:CC	acceptor_gain	1.0000
X:71061968:CT:C	acceptor_loss	1.0000
X:71061975:C:CT	acceptor_gain	1.0000
X:71061977:C:CT	acceptor_gain	1.0000
X:71061990:A:T	acceptor_gain	1.0000
X:71061993:C:CT	acceptor_gain	1.0000
X:71061996:A:C	acceptor_gain	1.0000
X:71062848:CCATA:C	donor_loss	1.0000
X:71062849:CATAC:C	donor_loss	1.0000
X:71062850:ATACC:A	donor_loss	1.0000
X:71062851:TA:T	donor_loss	1.0000
X:71062852:ACC:A	donor_loss	1.0000
X:71062853:CCTTG:C	donor_gain	1.0000
X:71062945:TTTGT:T	acceptor_gain	1.0000

AlphaMissense

1062 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:71061098:G:T	A136D	1.000
X:71061106:G:C	H133Q	1.000
X:71061106:G:T	H133Q	1.000
X:71061107:T:C	H133R	1.000
X:71061113:G:T	A131D	1.000
X:71061851:A:C	F126L	1.000
X:71061851:A:T	F126L	1.000
X:71061853:A:G	F126L	1.000
X:71061861:A:G	L123P	1.000
X:71061861:A:T	L123H	1.000
X:71061872:C:A	R119S	1.000
X:71061872:C:G	R119S	1.000
X:71061873:C:A	R119M	1.000
X:71062870:A:G	L82P	1.000
X:71062882:A:G	L78P	1.000
X:71062932:G:C	F61L	1.000
X:71062932:G:T	F61L	1.000
X:71062933:A:G	F61S	1.000
X:71062934:A:G	F61L	1.000
X:71062942:A:G	L58P	1.000
X:71062948:G:A	T56I	1.000
X:71061068:A:G	L146P	0.999
X:71061070:G:C	F145L	0.999
X:71061070:G:T	F145L	0.999
X:71061071:A:G	F145S	0.999
X:71061072:A:G	F145L	0.999
X:71061080:A:G	L142P	0.999
X:71061094:C:A	Q137H	0.999
X:71061094:C:G	Q137H	0.999
X:71061101:A:G	L135P	0.999

dbSNP variants (sampled 300 via entrez): RS1000118751 (X:71059807 A>G), RS1000469655 (X:71059136 C>T), RS1001046916 (X:71072565 A>C), RS1001248649 (X:71068427 GCACGCGCGCC>G), RS1001307739 (X:71059896 G>C), RS1001340396 (X:71060282 G>A), RS1001415680 (X:71072171 T>A,C), RS1001542710 (X:71069010 C>A,T), RS1001593682 (X:71069662 C>T), RS1001617042 (X:71070628 G>C), RS1001873554 (X:71066454 G>A), RS1001929086 (X:71067307 C>T), RS1002219814 (X:71073417 G>T), RS1002314927 (X:71062315 G>A), RS1002341118 (X:71062705 C>A,T)

Disease associations

OMIM: gene MIM:300883 | 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	3
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects binding, increases reaction	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Mifepristone	decreases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	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_B2GX	Abcam HeLa SNX12 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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