SPTSSB

Summary

SPTSSB (serine palmitoyltransferase small subunit B, HGNC:24045) is a protein-coding gene on chromosome 3q26.1, encoding Serine palmitoyltransferase small subunit B (Q8NFR3). Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases.

Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. SSSPTB is a small SPT subunit that stimulates SPT activity and confers acyl-CoA preference to the SPT catalytic heterodimer of SPTLC1 (MIM 605712) and either SPTLC2 (MIM 605713) or SPTLC3 (MIM 611120) (Han et al., 2009 [PubMed 19416851]).

Source: NCBI Gene 165679 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• MANE Select transcript: NM_001040100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24045
Approved symbol	SPTSSB
Name	serine palmitoyltransferase small subunit B
Location	3q26.1
Locus type	gene with protein product
Status	Approved
Aliases	ADMP, ssSPTb
Ensembl gene	ENSG00000196542
Ensembl biotype	protein_coding
OMIM	610412
Entrez	165679

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000359175, ENST00000497137, ENST00000497374, ENST00000620149, ENST00000886301, ENST00000935638, ENST00000941699, ENST00000941700

RefSeq mRNA: 2 — MANE Select: NM_001040100 NM_001040100, NM_001320679

CCDS: CCDS33887

Canonical transcript exons

ENST00000620149 — 3 exons

Exon	Start	End
ENSE00001683768	161359802	161359894
ENSE00001868748	161371435	161371517
ENSE00003753310	161344798	161346355

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 97.63.

FANTOM5 (CAGE): breadth broad, TPM avg 37.4145 / max 1062.9180, expressed in 404 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45389	27.2274	224
45393	3.7692	298
45396	2.6611	140
45388	1.6077	117
45386	0.4008	94
45390	0.3165	101
45385	0.3091	93
45387	0.2949	93
45394	0.2232	117
45391	0.2162	104

Top tissues by expression

236 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	97.63	gold quality
skin of abdomen	UBERON:0001416	91.37	gold quality
skin of leg	UBERON:0001511	90.59	gold quality
zone of skin	UBERON:0000014	88.58	gold quality
primary visual cortex	UBERON:0002436	86.60	gold quality
lower esophagus mucosa	UBERON:0035834	84.57	gold quality
islet of Langerhans	UBERON:0000006	83.75	gold quality
upper arm skin	UBERON:0004263	82.90	silver quality
cerebellar cortex	UBERON:0002129	82.14	gold quality
cerebellar hemisphere	UBERON:0002245	82.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.72	silver quality
prefrontal cortex	UBERON:0000451	81.70	gold quality
superior frontal gyrus	UBERON:0002661	81.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.21	gold quality
cerebellum	UBERON:0002037	80.78	gold quality
endothelial cell	CL:0000115	80.77	silver quality
postcentral gyrus	UBERON:0002581	79.80	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	79.13	gold quality
frontal cortex	UBERON:0001870	78.85	gold quality
occipital lobe	UBERON:0002021	78.68	gold quality
esophagus squamous epithelium	UBERON:0006920	78.49	silver quality
neocortex	UBERON:0001950	77.91	gold quality
nasal cavity epithelium	UBERON:0005384	77.00	gold quality
right frontal lobe	UBERON:0002810	76.87	gold quality
ventricular zone	UBERON:0003053	76.52	gold quality
esophagus mucosa	UBERON:0002469	76.47	gold quality
cerebral cortex	UBERON:0000956	75.95	gold quality
saliva-secreting gland	UBERON:0001044	75.62	gold quality
parietal lobe	UBERON:0001872	75.52	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	27.05
E-GEOD-81608	yes	15.19
E-ANND-3	yes	11.27
E-GEOD-83139	yes	9.43
E-ENAD-27	yes	9.10
E-HCAD-31	no	699.48

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• ADMP expression was seen predominantly in the prostate epithelium with weaker expression in the fibroblasts and endothelial cells. (PMID:15777716)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sptssb	ENSDARG00000091658
mus_musculus	Sptssb	ENSMUSG00000043461
rattus_norvegicus	Sptssb	ENSRNOG00000009388
drosophila_melanogaster	CG34194	FBGN0085223
drosophila_melanogaster	CG34293	FBGN0085322

Paralogs (1): SPTSSA (ENSG00000165389)

Protein

Protein identifiers

Serine palmitoyltransferase small subunit B — Q8NFR3 (reviewed: Q8NFR3)

Alternative names: Protein ADMP, Small subunit of serine palmitoyltransferase B

All UniProt accessions (1): Q8NFR3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. Within the SPT complex, SPTSSB stimulates the catalytic activity and plays a role in substrate specificity. SPT complexes with this subunit showing a preference for longer acyl-CoAs. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.

Subunit / interactions. Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expression is seen predominantly in the prostate epithelium with weaker expression in the fibroblasts and endothelial cells.

Induction. Expression is suppressed by androgens in the androgen-sensitive LNCaP cell line.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the SPTSS family. SPTSSB subfamily.

RefSeq proteins (2): NP_001035189, NP_001307608 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024512	Ser_palmitoyltrfase_ssu-like	Family

Pfam: PF11779

UniProt features (6 total): topological domain 3, transmembrane region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFR3-F1	86.94	0.46

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis
R-HSA-1430728	Metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 141 (showing top): GOZGIT_ESR1_TARGETS_DN, GOBP_POLYOL_METABOLIC_PROCESS, CTATGCA_MIR153, chr3q26, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, AGTCTTA_MIR499, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CAGCAGG_MIR370, GOBP_SPHINGOID_METABOLIC_PROCESS, E2F_Q3, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_DIOL_METABOLIC_PROCESS

GO Biological Process (6): endoplasmic reticulum organization (GO:0007029), sphingolipid biosynthetic process (GO:0030148), sphingosine biosynthetic process (GO:0046512), ceramide biosynthetic process (GO:0046513), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (2): serine C-palmitoyltransferase activity (GO:0004758), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), serine palmitoyltransferase complex (GO:0017059), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	1
endomembrane system organization	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
sphingosine metabolic process	1
diol biosynthetic process	1
sphingoid biosynthetic process	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
C-palmitoyltransferase activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
palmitoyltransferase complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPTSSB	SPTLC1	O15269	979
SPTSSB	SPTLC2	O15270	978
SPTSSB	SPTLC3	Q9NUV7	975
SPTSSB	ORMDL1	Q9P0S3	546
SPTSSB	SPTSSA	Q969W0	543
SPTSSB	LCLAT1	Q6UWP7	472
SPTSSB	ORMDL2	Q53FV1	449
SPTSSB	ST8SIA6	P61647	432
SPTSSB	TAF1D	Q9H5J8	428
SPTSSB	SYF2	O95926	387
SPTSSB	ORMDL3	Q8N138	384
SPTSSB	KDSR	Q06136	365
SPTSSB	CLEC3A	O75596	362
SPTSSB	KCNK4	Q9NYG8	362
SPTSSB	DEGS1	O15121	359

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SPTLC3	SPTSSB	psi-mi:“MI:0915”(physical association)	0.480
SPTLC3	SPTLC1	psi-mi:“MI:0914”(association)	0.480
SPTLC2	SPTSSB	psi-mi:“MI:0915”(physical association)	0.370
SPTLC1	SPTSSB	psi-mi:“MI:0915”(physical association)	0.370

ESM2 similar proteins: A5D7H3, A6NH52, A6QNL6, B0JZD0, B0S4Q1, B9EN89, F1S584, Q0IIK4, Q0VCK9, Q1RLT2, Q4G019, Q4PNJ2, Q5BJC1, Q5E978, Q5R9I4, Q5R9K4, Q5VXU1, Q5ZKJ0, Q66J05, Q66J44, Q68EQ9, Q6DED9, Q6DFT6, Q6GPZ5, Q6INE8, Q6NYY9, Q6ZMG9, Q810F1, Q8BXA5, Q8C172, Q8CIZ9, Q8IWA5, Q8NFR3, Q8R207, Q8VDR5, Q8WVP7, Q91ZQ0, Q924A5, Q925E8, Q940S0

Diamond homologs: B0S4Q1, B9EN89, Q0IIK4, Q1RLT2, Q4G019, Q5BJC1, Q5E978, Q66J05, Q66J44, Q6DFT6, Q6GPZ5, Q8NFR3, Q8R207, Q925E8, Q969W0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

618 predictions. Top by Δscore:

Variant	Effect	Δscore
3:161359892:CAT:C	acceptor_gain	1.0000
3:161359895:C:CC	acceptor_gain	1.0000
3:161372714:C:A	donor_gain	1.0000
3:161346352:TGTC:T	acceptor_gain	0.9900
3:161346353:GTCC:G	acceptor_loss	0.9900
3:161346354:TCC:T	acceptor_loss	0.9900
3:161346355:CCTG:C	acceptor_loss	0.9900
3:161346356:C:A	acceptor_loss	0.9900
3:161346356:C:CC	acceptor_gain	0.9900
3:161346357:T:A	acceptor_loss	0.9900
3:161359796:A:AC	donor_gain	0.9900
3:161359797:C:CC	donor_gain	0.9900
3:161359890:CTCAT:C	acceptor_gain	0.9900
3:161359891:TCAT:T	acceptor_gain	0.9900
3:161359892:CATC:C	acceptor_gain	0.9900
3:161359894:TC:T	acceptor_loss	0.9900
3:161359896:T:G	acceptor_loss	0.9900
3:161372660:CG:C	donor_gain	0.9900
3:161346351:TTGTC:T	acceptor_gain	0.9800
3:161353898:C:A	donor_gain	0.9800
3:161359893:AT:A	acceptor_gain	0.9800
3:161372466:C:CA	donor_gain	0.9800
3:161346354:TC:T	acceptor_gain	0.9700
3:161346355:CC:C	acceptor_gain	0.9700
3:161346358:G:C	acceptor_loss	0.9700
3:161372467:C:A	donor_gain	0.9700
3:161372660:CGCT:C	donor_gain	0.9700
3:161372732:A:AC	donor_gain	0.9700
3:161346353:GTC:G	acceptor_gain	0.9600
3:161371760:AGT:A	donor_gain	0.9600

AlphaMissense

496 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:161346168:A:C	F52L	0.996
3:161346168:A:T	F52L	0.996
3:161346170:A:G	F52L	0.996
3:161346239:A:G	W29R	0.993
3:161346239:A:T	W29R	0.993
3:161346261:G:C	S21R	0.992
3:161346261:G:T	S21R	0.992
3:161346263:T:G	S21R	0.992
3:161346179:C:G	A49P	0.991
3:161346193:A:C	M44R	0.990
3:161346235:T:A	E30V	0.990
3:161346178:G:T	A49D	0.989
3:161346145:G:T	A60D	0.988
3:161346163:G:T	P54Q	0.988
3:161346193:A:T	M44K	0.988
3:161346169:A:G	F52S	0.986
3:161346185:A:C	Y47D	0.986
3:161346277:T:G	Q16P	0.986
3:161346196:G:T	A43D	0.984
3:161346237:C:A	W29C	0.984
3:161346237:C:G	W29C	0.984
3:161346135:A:C	F63L	0.983
3:161346135:A:T	F63L	0.983
3:161346137:A:G	F63L	0.983
3:161346163:G:C	P54R	0.983
3:161346235:T:G	E30A	0.983
3:161346172:A:T	V51D	0.982
3:161346192:C:A	M44I	0.982
3:161346192:C:G	M44I	0.982
3:161346192:C:T	M44I	0.982

dbSNP variants (sampled 300 via entrez): RS1000057879 (3:161361400 G>A,T), RS1000159549 (3:161370277 C>G,T), RS1000234840 (3:161346803 A>G), RS1000486584 (3:161348788 CTT>C), RS1000645281 (3:161365566 T>G), RS1000679781 (3:161352596 G>A), RS1000728453 (3:161352276 T>C,G), RS1000778839 (3:161349866 T>A,C), RS1000793062 (3:161358846 A>C), RS1000860430 (3:161371704 A>G), RS1001241683 (3:161368245 A>T), RS1001418250 (3:161347077 T>C), RS1001497951 (3:161365213 T>C), RS1001564638 (3:161372104 G>A), RS1001574654 (3:161365593 C>G)

Disease associations

OMIM: gene MIM:610412 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003460_1	IgG1 response to Plasmodium falciparum antigen (GLURP)	9.000000e-06
GCST007326_14	Number of sexual partners	2.000000e-08
GCST007565_43	Morning person	2.000000e-14
GCST009325_95	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	5.000000e-10
GCST010991_36	Parkinson’s disease	6.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007810	Plasmodium falciparum antigen IgG1 measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067597 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Serine palmitoyltransferase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 18 [PMID: 32330443]	Inhibition	5.77	pKi

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.66	IC50	2180	nM	GAMBOGIC ACID

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(Z)-4-[(1S,2S,8R,17S,19R)-12-hydroxy-8,21,21-trimethyl-5-(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-14,18-dioxo-3,7,20-trioxahexacyclo[15.4.1.02,15.02,19.04,13.06,11]docosa-4(13),5,9,11,15-pentaen-19-yl]-2-methylbut-2-enoic acid	2084160: Inhibition of SPTSSB (unknown origin) expressed in HEK293T cells	ic50	2.1800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
aminomethylphosphonic acid (AMPA)	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
ascorbate-2-phosphate	affects cotreatment, decreases expression, affects binding	1
ethyl-p-hydroxybenzoate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
azaspiracid	decreases expression	1
Chir 99021	affects binding, affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
XAV939	affects binding, affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Ascorbic Acid	affects binding, affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Coal	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5524633	Binding	Inhibition of SPTSSB (unknown origin) expressed in HEK293T cells	Modulators for palmitoylation of proteins and small molecules. — Eur J Med Chem

Clinical trials (associated diseases)

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