SNX21

Summary

SNX21 (sorting nexin family member 21, HGNC:16154) is a protein-coding gene on chromosome 20q13.12, encoding Sorting nexin-21 (Q969T3). Binds to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)) and phosphatidylinositol 4,5-bisphosphate.

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. The specific function of this protein has not been determined. Multiple transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 90203 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_033421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16154
Approved symbol	SNX21
Name	sorting nexin family member 21
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ337O18.4, SNX-L
Ensembl gene	ENSG00000124104
Ensembl biotype	protein_coding
OMIM	619200
Entrez	90203

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000342644, ENST00000344780, ENST00000372541, ENST00000372542, ENST00000372547, ENST00000462307, ENST00000465997, ENST00000466252, ENST00000472219, ENST00000478230, ENST00000486336, ENST00000491381, ENST00000614929

RefSeq mRNA: 4 — MANE Select: NM_033421 NM_001042632, NM_001042633, NM_033421, NM_152897

CCDS: CCDS13376, CCDS13377, CCDS42883

Canonical transcript exons

ENST00000491381 — 4 exons

Exon	Start	End
ENSE00003620951	45834959	45835116
ENSE00003633033	45834201	45834468
ENSE00003844486	45840639	45843276
ENSE00003848971	45833799	45833940

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 94.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5379 / max 131.0502, expressed in 1649 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184951	6.3350	1541
184954	4.2050	1199
184953	3.4847	1270
184952	2.1676	1083
184950	1.3456	758

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	94.49	gold quality
right ovary	UBERON:0002118	93.94	gold quality
left ovary	UBERON:0002119	93.92	gold quality
skin of abdomen	UBERON:0001416	93.67	gold quality
right coronary artery	UBERON:0001625	93.45	gold quality
endothelial cell	CL:0000115	93.42	gold quality
right adrenal gland cortex	UBERON:0035827	93.32	gold quality
zone of skin	UBERON:0000014	93.27	gold quality
mucosa of stomach	UBERON:0001199	93.27	gold quality
right adrenal gland	UBERON:0001233	93.17	gold quality
left adrenal gland cortex	UBERON:0035825	92.98	gold quality
adrenal cortex	UBERON:0001235	92.93	gold quality
left uterine tube	UBERON:0001303	92.89	gold quality
left adrenal gland	UBERON:0001234	92.68	gold quality
endocervix	UBERON:0000458	92.59	gold quality
descending thoracic aorta	UBERON:0002345	92.40	gold quality
coronary artery	UBERON:0001621	92.33	gold quality
body of uterus	UBERON:0009853	92.29	gold quality
left coronary artery	UBERON:0001626	92.24	gold quality
popliteal artery	UBERON:0002250	92.24	gold quality
tibial artery	UBERON:0007610	92.23	gold quality
aorta	UBERON:0000947	91.98	gold quality
thoracic aorta	UBERON:0001515	91.71	gold quality
ascending aorta	UBERON:0001496	91.64	gold quality
adrenal gland	UBERON:0002369	91.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.43	gold quality
ovary	UBERON:0000992	91.36	gold quality
ectocervix	UBERON:0012249	91.25	gold quality
layer of synovial tissue	UBERON:0007616	91.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting SNX21, 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-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-6865-3P	97.54	64.67	684

Literature-anchored findings (GeneRIF, showing 2)

• Data suggest that human sorting nexin-L (SNX-L) may be a regulatory gene involved in receptor protein degradation during embryonic liver development. (PMID:12459172)
• The N-terminal extension of SNX21 interacts with huntingtin and recruit Htt to an endosomal population. (PMID:30072438)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx21	ENSDARG00000062770
mus_musculus	Snx21	ENSMUSG00000050373
drosophila_melanogaster	Snx21	FBGN0031457

Paralogs (1): SNX20 (ENSG00000167208)

Protein

Protein identifiers

Sorting nexin-21 — Q969T3 (reviewed: Q969T3)

Alternative names: Sorting nexin L

All UniProt accessions (5): A0A0S2Z632, Q969T3, Q05DJ0, Q5JZH3, Q5JZH4

UniProt curated annotations — full annotation on UniProt →

Function. Binds to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)) and phosphatidylinositol 4,5-bisphosphate. May be involved in several stages of intracellular trafficking.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasmic vesicle membrane. Early endosome membrane.

Tissue specificity. Highly expressed in fetus liver, but only weakly expressed in brain, skeleton muscle, smooth muscle, and cardiac muscle, kidney, and adrenal gland.

Domain organisation. The PX domain mediates specific binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)).

Similarity. Belongs to the sorting nexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q969T3-1	1	yes
Q969T3-2	2
Q969T3-3	3

RefSeq proteins (4): NP_001036097, NP_001036098, NP_219489, NP_690857 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR039937	SNX20/SNX21	Family

Pfam: PF00787

UniProt features (14 total): binding site 4, splice variant 3, compositionally biased region 3, chain 1, domain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969T3-F1	76.37	0.53

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): 171; 173; 198; 212

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, BEIER_GLIOMA_STEM_CELL_DN, AACTTT_UNKNOWN, RYTTCCTG_ETS2_B, GOCC_EARLY_ENDOSOME_MEMBRANE, GOMF_PHOSPHATIDYLINOSITOL_4_5_BISPHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, MODULE_13, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BISPHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_3_PHOSPHATE_BINDING, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING

GO Biological Process (1): protein transport (GO:0015031)

GO Molecular Function (6): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515), lipid binding (GO:0008289), phosphatidylinositol binding (GO:0035091)

GO Cellular Component (5): early endosome membrane (GO:0031901), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol phosphate binding	2
binding	2
cytoplasmic vesicle	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
phosphatidylinositol bisphosphate binding	1
phospholipid binding	1
anion binding	1
early endosome	1
endosome membrane	1
endomembrane system	1
cellular anatomical structure	1
vesicle membrane	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX21	SNX2	P82862	607
SNX21	SNX29	Q8TEQ0	600
SNX21	SPATA25	Q9BR10	532
SNX21	SNX11	Q9Y5W9	528
SNX21	WFDC10B	Q8IUB3	526
SNX21	ZSWIM1	Q9BR11	507
SNX21	WFDC3	Q8IUB2	506
SNX21	SNX16	P57768	505
SNX21	SNX3	O60493	496
SNX21	SNX17	Q15036	488
SNX21	SNX24	Q9Y343	485
SNX21	SNX22	Q96L94	472
SNX21	HTT	P42858	461
SNX21	HS1BP3	Q53T59	459
SNX21	SNX12	Q9UMY4	450

IntAct

12 interactions, top by confidence:

A	B	Type	Score
MARCKSL1	NMT2	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
SNX21	LRRK1	psi-mi:“MI:0407”(direct interaction)	0.440
SNX21	COX6A2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
SNX21	POLR1G	psi-mi:“MI:0914”(association)	0.350
MSRB3	SPOP	psi-mi:“MI:0914”(association)	0.350
SNX21	RBP4	psi-mi:“MI:0914”(association)	0.350
SNX21	ACOT8	psi-mi:“MI:0914”(association)	0.350
SNX21	PI4KA	psi-mi:“MI:0914”(association)	0.350

BioGRID (87): SNX21 (Affinity Capture-MS), TUBB7P (Affinity Capture-MS), SNX21 (Affinity Capture-MS), HTT (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), EIF2A (Affinity Capture-MS), TRIM65 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), EME1 (Affinity Capture-MS), VPS13B (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), DDX11 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), BBS9 (Affinity Capture-MS)

ESM2 similar proteins: A1L515, A4D2P6, A6QQD2, A8VU90, E1BDF2, O75808, O88995, P0CG25, P22083, Q0IIA6, Q2TA57, Q3B7L1, Q3MIP1, Q3U5Q7, Q3UR50, Q3UR97, Q3UV16, Q400G9, Q5BKX5, Q5EBM0, Q5GH72, Q5SZI1, Q5TM19, Q5U4P2, Q62994, Q659K9, Q6PRD1, Q7Z736, Q861W0, Q86UR1, Q8BNN1, Q8C0R7, Q8CG70, Q8IUW3, Q8IVL6, Q8N398, Q8NAG6, Q8NCW0, Q8R2H1, Q8VCE9

Diamond homologs: Q2T9W1, Q3UR97, Q5BK61, Q7Z614, Q969T3, Q9D2Y5, Q9Y343, Q148E7, Q4V896, Q5AG40, Q5RA67, Q8BLK9, Q8R2S1, Q91WE1, Q96S38, Q9C0U7, Q9NRS6, Q9Y6S9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

894 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45834405:G:GT	donor_gain	1.0000
20:45834414:G:GT	donor_gain	1.0000
20:45834479:G:GT	donor_gain	1.0000
20:45834482:G:GT	donor_gain	1.0000
20:45835110:G:GG	donor_gain	1.0000
20:45835114:GTG:G	donor_gain	1.0000
20:45840421:T:A	acceptor_gain	1.0000
20:45840424:T:A	acceptor_gain	1.0000
20:45840429:T:TA	acceptor_gain	1.0000
20:45840430:G:A	acceptor_gain	1.0000
20:45840635:GCA:G	acceptor_loss	1.0000
20:45840636:CAG:C	acceptor_loss	1.0000
20:45840637:A:AG	acceptor_gain	1.0000
20:45840638:G:GA	acceptor_gain	1.0000
20:45840638:GC:G	acceptor_gain	1.0000
20:45840638:GCT:G	acceptor_gain	1.0000
20:45840638:GCTC:G	acceptor_gain	1.0000
20:45840638:GCTCT:G	acceptor_gain	1.0000
20:45833938:G:GT	donor_gain	0.9900
20:45833978:GGTCC:G	donor_gain	0.9900
20:45834547:GGCGC:G	donor_gain	0.9900
20:45834548:GCGC:G	donor_gain	0.9900
20:45834551:C:G	donor_gain	0.9900
20:45834956:CAG:C	acceptor_loss	0.9900
20:45834957:A:AG	acceptor_gain	0.9900
20:45834958:G:GA	acceptor_gain	0.9900
20:45834958:GAAC:G	acceptor_gain	0.9900
20:45835115:TGGTG:T	donor_loss	0.9900
20:45835117:G:GA	donor_loss	0.9900
20:45835117:G:GG	donor_gain	0.9900

AlphaMissense

2385 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45840715:T:C	F175S	0.998
20:45840785:G:C	K198N	0.998
20:45840785:G:T	K198N	0.998
20:45840800:T:A	N203K	0.998
20:45840800:T:G	N203K	0.998
20:45840802:T:C	F204S	0.998
20:45840817:T:A	I209N	0.998
20:45840705:T:C	Y172H	0.997
20:45840775:T:C	F195S	0.997
20:45840783:A:G	K198E	0.997
20:45840825:C:A	R212S	0.997
20:45840838:T:C	F216S	0.997
20:45840705:T:G	Y172D	0.996
20:45840706:A:G	Y172C	0.996
20:45840802:T:G	F204C	0.996
20:45835082:C:A	A138D	0.995
20:45840801:T:C	F204L	0.995
20:45840803:T:A	F204L	0.995
20:45840803:T:G	F204L	0.995
20:45840642:T:G	Y151D	0.994
20:45840778:C:A	P196H	0.994
20:45840784:A:T	K198M	0.994
20:45840798:A:G	N203D	0.994
20:45835115:T:A	V149E	0.993
20:45840642:T:C	Y151H	0.993
20:45840705:T:A	Y172N	0.993
20:45840736:T:C	L182P	0.993
20:45840777:C:T	P196S	0.993
20:45840784:A:C	K198T	0.993
20:45840817:T:G	I209S	0.993

dbSNP variants (sampled 300 via entrez): RS1000972499 (20:45833754 C>A,T), RS1001109810 (20:45833347 T>C), RS1001281015 (20:45839560 C>A), RS1001347726 (20:45839721 C>A,G,T), RS1001693283 (20:45832189 A>G), RS1002196964 (20:45833958 G>A,T), RS1002319046 (20:45842187 C>G,T), RS1002729036 (20:45833520 C>T), RS1003210685 (20:45835815 A>C), RS1003324229 (20:45843749 C>A,T), RS1003589310 (20:45835513 A>G,T), RS1004314295 (20:45839572 T>G), RS1004345275 (20:45839388 C>A,G), RS1004655386 (20:45833918 G>A,C), RS1004668755 (20:45832884 A>C,T)

Disease associations

OMIM: gene MIM:619200 | 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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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