SPNS3

Summary

SPNS3 (SPNS lysolipid transporter 3, sphingosine-1-phosphate (putative), HGNC:28433) is a protein-coding gene on chromosome 17p13.2, encoding Protein spinster homolog 3 (Q6ZMD2). Sphingolipid transporter.

Predicted to enable transmembrane transporter activity. Predicted to be involved in lipid transport and transmembrane transport. Predicted to be active in membrane.

Source: NCBI Gene 201305 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_182538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28433
Approved symbol	SPNS3
Name	SPNS lysolipid transporter 3, sphingosine-1-phosphate (putative)
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC29671, SLC63A3
Ensembl gene	ENSG00000182557
Ensembl biotype	protein_coding
OMIM	611701
Entrez	201305

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 protein_coding

ENST00000355530, ENST00000572078, ENST00000575185, ENST00000575194, ENST00000575796, ENST00000576069, ENST00000714275, ENST00000714276, ENST00000714277

RefSeq mRNA: 2 — MANE Select: NM_182538 NM_001320449, NM_182538

CCDS: CCDS11045

Canonical transcript exons

ENST00000355530 — 12 exons

Exon	Start	End
ENSE00003533242	4446896	4446962
ENSE00003534899	4478572	4478637
ENSE00003567248	4486412	4486583
ENSE00003646641	4446048	4446199
ENSE00004023416	4487806	4488204
ENSE00004023417	4486228	4486326
ENSE00004023418	4445032	4445168
ENSE00004023420	4439658	4439723
ENSE00004023421	4449235	4449387
ENSE00004023422	4453016	4453205
ENSE00004023424	4448155	4448303
ENSE00004023426	4433940	4434166

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 86.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9290 / max 406.2253, expressed in 180 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158891	1.5931	94
158890	0.3176	114
158892	0.0182	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.96	gold quality
granulocyte	CL:0000094	79.94	gold quality
bone marrow	UBERON:0002371	79.63	gold quality
monocyte	CL:0000576	78.08	gold quality
leukocyte	CL:0000738	77.96	gold quality
bone marrow cell	CL:0002092	77.73	gold quality
metanephros cortex	UBERON:0010533	77.66	gold quality
upper arm skin	UBERON:0004263	76.28	gold quality
blood	UBERON:0000178	74.26	gold quality
right adrenal gland cortex	UBERON:0035827	73.83	gold quality
right adrenal gland	UBERON:0001233	73.69	gold quality
right lobe of liver	UBERON:0001114	73.17	gold quality
kidney epithelium	UBERON:0004819	72.82	gold quality
myocardium	UBERON:0002349	72.46	gold quality
left adrenal gland cortex	UBERON:0035825	72.43	gold quality
spleen	UBERON:0002106	72.24	gold quality
left adrenal gland	UBERON:0001234	71.62	gold quality
adrenal cortex	UBERON:0001235	71.59	gold quality
lower esophagus mucosa	UBERON:0035834	71.01	gold quality
metanephros	UBERON:0000081	70.53	gold quality
ileal mucosa	UBERON:0000331	70.43	silver quality
vermiform appendix	UBERON:0001154	70.43	gold quality
epithelial cell of pancreas	CL:0000083	70.14	gold quality
lymph node	UBERON:0000029	70.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	70.10	gold quality
left ventricle myocardium	UBERON:0006566	69.85	gold quality
trabecular bone tissue	UBERON:0002483	69.77	silver quality
adult mammalian kidney	UBERON:0000082	69.27	gold quality
jejunal mucosa	UBERON:0000399	68.72	silver quality
amniotic fluid	UBERON:0000173	68.61	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	22.71
E-MTAB-9067	yes	15.65
E-ANND-3	yes	5.08
E-CURD-112	no	3.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting SPNS3, 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-766-3P	99.47	65.24	1811
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-6736-3P	96.98	65.22	1342

Literature-anchored findings (GeneRIF, showing 2)

• Bioinformatics-based identification of SPNS3 (Spinster homolog 3) as a prognostic biomarker of apoptosis resistance in acute myeloid leukemia. (PMID:34608834)
• Upregulation of FHL1, SPNS3, and MPZL2 predicts poor prognosis in pediatric acute myeloid leukemia patients with FLT3-ITD mutation. (PMID:35249471)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	spns3	ENSDARG00000035459
mus_musculus	Spns3	ENSMUSG00000020798
rattus_norvegicus	Spns3	ENSRNOG00000015873
drosophila_melanogaster	spin	FBGN0086676
caenorhabditis_elegans		WBGENE00007549
caenorhabditis_elegans		WBGENE00008033
caenorhabditis_elegans		WBGENE00008598
caenorhabditis_elegans		WBGENE00013739

Paralogs (2): SPNS1 (ENSG00000169682), SPNS2 (ENSG00000183018)

Protein

Protein identifiers

Protein spinster homolog 3 — Q6ZMD2 (reviewed: Q6ZMD2)

All UniProt accessions (3): Q6ZMD2, A0AAQ5BHT9, I3L3W7

UniProt curated annotations — full annotation on UniProt →

Function. Sphingolipid transporter.

Subcellular location. Membrane.

Similarity. Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMD2-1	1	yes
Q6ZMD2-2	2

RefSeq proteins (2): NP_001307378, NP_872344* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR044770	MFS_spinster-like	Family

Pfam: PF07690

UniProt features (21 total): transmembrane region 12, sequence variant 3, region of interest 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMD2-F1	85.21	0.67

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, RYTTCCTG_ETS2_B, GOBP_LIPID_LOCALIZATION, GOBP_TRANSMEMBRANE_TRANSPORT, ETS_Q4, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_TRANSPORTER_ACTIVITY, CHYLA_CBFA2T3_TARGETS_UP, WIERENGA_STAT5A_TARGETS_DN, E2F3_UP.V1_DN, MYC_UP.V1_DN, SRC_UP.V1_DN

GO Biological Process (2): lipid transport (GO:0006869), transmembrane transport (GO:0055085)

GO Molecular Function (2): transmembrane transporter activity (GO:0022857), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
lipid localization	1
cellular process	1
transporter activity	1
transmembrane transport	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPNS3	SLC22A1	O15245	888
SPNS3	SLC67A2	Q8NBP5	591
SPNS3	SLC75A1	Q14728	587
SPNS3	SVOPL	Q8N434	570
SPNS3	SLC33A2	Q96ES6	567
SPNS3	MFSD11	O43934	548
SPNS3	SLC61A1	Q6N075	548
SPNS3	MFSD2B	A6NFX1	541
SPNS3	SVOP	Q8N4V2	523
SPNS3	UNC93A	Q86WB7	495
SPNS3	PARD6A	Q9NPB6	488
SPNS3	SLC68A1	Q14CX5	486
SPNS3	MFSD6L	Q8IWD5	483
SPNS3	CARHSP1	Q9Y2V2	481
SPNS3	DOCK7	Q96N67	459

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SPNS3	CLCC1	psi-mi:“MI:0915”(physical association)	0.620
SPNS3	PIGR	psi-mi:“MI:0914”(association)	0.350
SPNS3	PTPN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), SPNS3 (Two-hybrid), SPNS3 (Two-hybrid), SPNS3 (Two-hybrid), SPNS3 (Two-hybrid), SPNS3 (Two-hybrid), SPNS3 (Two-hybrid), SPNS3 (Two-hybrid), LOC100507537 (Two-hybrid), CLCC1 (Affinity Capture-MS), LCN1 (Affinity Capture-MS), LTF (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), PIGR (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

Diamond homologs: A2CER7, A2SWM2, A8WGF7, B0JZE1, P96712, Q08DX7, Q2YDU8, Q5XGK0, Q6ZMD2, Q7ZU13, Q8IVW8, Q8R0G7, Q91VM4, Q9D232, Q9GQQ0, Q9H2V7, O31762, Q796Q1, S0DW25, Q9Y226, A4WE10, A6TDH1, A7MR37, A8AP55, B5XUP3, B7LNJ1, Q0IZQ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2337 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4439719:GACTG:G	donor_gain	1.0000
17:4446046:A:AG	acceptor_gain	1.0000
17:4446047:G:GG	acceptor_gain	1.0000
17:4446047:GT:G	acceptor_gain	1.0000
17:4446072:C:CA	acceptor_gain	1.0000
17:4446197:AAGG:A	donor_loss	1.0000
17:4446198:AGGT:A	donor_loss	1.0000
17:4446201:T:G	donor_loss	1.0000
17:4446894:AGT:A	acceptor_gain	1.0000
17:4446895:GTG:G	acceptor_gain	1.0000
17:4446961:GA:G	donor_gain	1.0000
17:4446963:G:GG	donor_gain	1.0000
17:4453010:CATCA:C	acceptor_loss	1.0000
17:4453011:A:AG	acceptor_gain	1.0000
17:4453011:ATCAG:A	acceptor_loss	1.0000
17:4453012:T:G	acceptor_gain	1.0000
17:4453012:TCA:T	acceptor_loss	1.0000
17:4453013:CAGCC:C	acceptor_loss	1.0000
17:4453014:A:AC	acceptor_loss	1.0000
17:4453014:A:AG	acceptor_gain	1.0000
17:4453014:AGCCT:A	acceptor_gain	1.0000
17:4453015:G:GA	acceptor_gain	1.0000
17:4453015:GC:G	acceptor_gain	1.0000
17:4453015:GCC:G	acceptor_gain	1.0000
17:4453015:GCCT:G	acceptor_gain	1.0000
17:4453015:GCCTG:G	acceptor_gain	1.0000
17:4453202:CTAT:C	donor_gain	1.0000
17:4453203:TAT:T	donor_gain	1.0000
17:4453204:AT:A	donor_gain	1.0000
17:4453204:ATGTA:A	donor_loss	1.0000

AlphaMissense

3255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4486306:A:C	S420R	0.992
17:4486308:C:A	S420R	0.992
17:4486308:C:G	S420R	0.992
17:4446099:A:C	S152R	0.987
17:4446101:C:A	S152R	0.987
17:4446101:C:G	S152R	0.987
17:4446138:T:C	F165L	0.983
17:4446140:C:A	F165L	0.983
17:4446140:C:G	F165L	0.983
17:4453134:A:C	S348R	0.976
17:4453136:C:A	S348R	0.976
17:4453136:C:G	S348R	0.976
17:4486478:A:C	S449R	0.973
17:4486480:C:A	S449R	0.973
17:4486480:C:G	S449R	0.973
17:4434121:T:C	C52R	0.966
17:4446174:T:C	F177L	0.960
17:4446176:C:A	F177L	0.960
17:4446176:C:G	F177L	0.960
17:4449239:A:C	S259R	0.959
17:4449241:T:A	S259R	0.959
17:4449241:T:G	S259R	0.959
17:4446091:G:A	G149D	0.958
17:4446195:G:A	G184R	0.957
17:4446195:G:C	G184R	0.957
17:4453057:G:A	G322E	0.957
17:4434132:C:A	N55K	0.956
17:4434132:C:G	N55K	0.956
17:4445116:G:A	G117D	0.956
17:4446904:G:A	G188D	0.956

dbSNP variants (sampled 300 via entrez): RS1000005581 (17:4476840 C>G), RS1000116387 (17:4455605 C>T), RS1000144381 (17:4484673 C>A,G,T), RS1000153229 (17:4450856 C>T), RS1000163280 (17:4441787 G>A,C), RS1000420195 (17:4450994 C>T), RS1000442214 (17:4467337 G>A), RS1000448674 (17:4466776 C>T), RS1000458387 (17:4442322 C>T), RS1000498109 (17:4432939 C>T), RS1000557047 (17:4438064 G>T), RS1000564955 (17:4466454 C>T), RS1000587515 (17:4471731 G>A,C), RS1000602634 (17:4473083 C>T), RS1000673699 (17:4460861 G>A)

Disease associations

OMIM: gene MIM:611701 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_49	Obesity-related traits	6.000000e-06
GCST004746_49	Small cell lung carcinoma	2.000000e-06
GCST006281_13	Coronary artery disease in type 1 diabetes	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC63 Sphingosine phosphate transporters

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
fluorene-9-bisphenol	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	affects methylation	1
perfluorooctanoic acid	increases expression	1
1-hydroxypyrene	decreases expression	1
enniatins	increases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Estradiol	decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4WN	LS180-SPNS3-KO-c3	Cancer cell line	Female
CVCL_D4WP	LS180-SPNS3-KO-c6	Cancer cell line	Female

Clinical trials (associated diseases)

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