SPTSSA

Summary

SPTSSA (serine palmitoyltransferase small subunit A, HGNC:20361) is a protein-coding gene on chromosome 14q13.1, encoding Serine palmitoyltransferase small subunit A (Q969W0). 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. It is a selective cancer dependency (DepMap: 35.4% of cell lines).

Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. SSSPTA 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 171546 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic paraplegia 90A, autosomal dominant (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 17 total — 2 pathogenic
• Phenotypes (HPO): 25
• Cancer dependency (DepMap): dependent in 35.4% of screened cell lines
• MANE Select transcript: NM_138288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20361
Approved symbol	SPTSSA
Name	serine palmitoyltransferase small subunit A
Location	14q13.1
Locus type	gene with protein product
Status	Approved
Aliases	ssSPTa
Ensembl gene	ENSG00000165389
Ensembl biotype	protein_coding
OMIM	613540
Entrez	171546

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000298130

RefSeq mRNA: 1 — MANE Select: NM_138288 NM_138288

CCDS: CCDS9647

Canonical transcript exons

ENST00000298130 — 2 exons

Exon	Start	End
ENSE00001092664	34432788	34435304
ENSE00001092666	34462096	34462240

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.1295 / max 707.8386, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142786	67.0964	1820
142787	5.0331	1723

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	96.71	gold quality
right adrenal gland cortex	UBERON:0035827	96.67	gold quality
adrenal cortex	UBERON:0001235	96.57	gold quality
left adrenal gland cortex	UBERON:0035825	96.51	gold quality
colonic mucosa	UBERON:0000317	96.42	gold quality
left adrenal gland	UBERON:0001234	96.41	gold quality
right adrenal gland	UBERON:0001233	96.33	gold quality
decidua	UBERON:0002450	96.22	gold quality
lower lobe of lung	UBERON:0008949	96.12	gold quality
parotid gland	UBERON:0001831	95.61	gold quality
right lung	UBERON:0002167	95.20	gold quality
palpebral conjunctiva	UBERON:0001812	95.14	gold quality
adrenal gland	UBERON:0002369	94.93	gold quality
seminal vesicle	UBERON:0000998	94.23	gold quality
rectum	UBERON:0001052	93.94	gold quality
penis	UBERON:0000989	93.90	gold quality
monocyte	CL:0000576	93.80	gold quality
mononuclear cell	CL:0000842	93.73	gold quality
heart right ventricle	UBERON:0002080	93.73	gold quality
cauda epididymis	UBERON:0004360	93.43	gold quality
leukocyte	CL:0000738	93.23	gold quality
saliva-secreting gland	UBERON:0001044	93.19	gold quality
eye	UBERON:0000970	93.14	gold quality
upper lobe of lung	UBERON:0008948	93.04	gold quality
minor salivary gland	UBERON:0001830	92.86	gold quality
upper lobe of left lung	UBERON:0008952	92.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.72	gold quality
skin of hip	UBERON:0001554	92.57	gold quality
mucosa of transverse colon	UBERON:0004991	92.52	gold quality
corpus epididymis	UBERON:0004359	92.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	2806.89
E-MTAB-10885	yes	1959.62
E-MTAB-10855	yes	1950.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting SPTSSA, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-552-5P	99.93	68.56	1583

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 35.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• discovery of 2 proteins, ssSPTa and ssSPTb, which each interacts with both hLCB1 and hLCB2, suggesting[ssSPTa] [ssSPTb] (PMID:19416851)
• ssSPTa is identified as an LPIAT1-interacting protein. (PMID:23510452)
• A genome-wide CRISPR/Cas9 screen reveals that the aryl hydrocarbon receptor stimulates sphingolipid levels. (PMID:32029474)
• SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia. (PMID:36718090)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sptssa	ENSDARG00000071203
mus_musculus	Sptssa	ENSMUSG00000044408
rattus_norvegicus	Sptssa	ENSRNOG00000004292
drosophila_melanogaster	CG34194	FBGN0085223
drosophila_melanogaster	CG34293	FBGN0085322

Paralogs (1): SPTSSB (ENSG00000196542)

Protein

Protein identifiers

Serine palmitoyltransferase small subunit A — Q969W0 (reviewed: Q969W0)

Alternative names: Small subunit of serine palmitoyltransferase A

All UniProt accessions (1): Q969W0

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, SPTSSA stimulates the catalytic activity and plays a role in substrate specificity, which depends upon the overall complex composition. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. Independently of its action as a SPT component, may be involved in MBOAT7 localization to mitochondria-associated membranes, a membrane bridge between the endoplasmic reticulum and mitochondria, may hence affect MBOAT7-catalyzed incorporation of arachidonic acid into phosphatidylinositol.

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. Interacts with MBOAT7; the interaction plays a role in MBOAT7 localization to mitochondria-associated membranes.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Spastic paraplegia 90A, autosomal dominant (SPG90A) [MIM:620416] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or weakness and stiffness may spread to other parts of the body. SPG90A affected individuals have motor impairment and progressive lower extremity spasticity as well as neurologic findings, cognitive impairment, and hearing loss. The disease may be caused by variants affecting the gene represented in this entry. Spastic paraplegia 90B, autosomal recessive (SPG90B) [MIM:620417] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or weakness and stiffness may spread to other parts of the body. SPG90B is an autosomal recessive form characterized by motor impairment and progressive lower extremity spasticity as well as neurologic findings, cognitive impairment, and hearing loss. The disease may be caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the SPTSS family. SPTSSA subfamily.

RefSeq proteins (1): NP_612145* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024512	Ser_palmitoyltrfase_ssu-like	Family
IPR051900	SPT_small_subunit	Family

Pfam: PF11779

Enzyme classification (BRENDA):

• EC 2.3.1.50 — serine C-palmitoyltransferase (BRENDA: 23 organisms, 127 substrates, 64 inhibitors, 70 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-SERINE	0.26–10.6	28
PALMITOYL-COA	0.019–1.2	18
MYRISTOYL-COA	0.03–0.097	3
CAPROYL-COA	0.68–0.9	2
L-ALANINE	9.6–110	2
LAUROYL-COA	0.25–0.56	2
GLYCINE	77	1
L-HOMOSERINE	82	1
STEAROYL-COA	0.0129	1
[1,2,3-13C,2-15N] L-SERINE	1.79	1
[2,3,3-D] L-SERINE	4.09	1
[2-13C] L-SERINE	3.64	1
[3,3-D] L-SERINE	2.72	1

UniProt features (15 total): helix 4, topological domain 3, transmembrane region 2, mutagenesis site 2, chain 1, sequence conflict 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
7K0K	ELECTRON MICROSCOPY	2.6
7YIY	ELECTRON MICROSCOPY	2.7
7K0M	ELECTRON MICROSCOPY	2.9
7YIU	ELECTRON MICROSCOPY	2.9
7YJ2	ELECTRON MICROSCOPY	2.9
7K0J	ELECTRON MICROSCOPY	3.1
7K0N	ELECTRON MICROSCOPY	3.1
7K0O	ELECTRON MICROSCOPY	3.1
7K0P	ELECTRON MICROSCOPY	3.1
7YJ1	ELECTRON MICROSCOPY	3.1
7CQI	ELECTRON MICROSCOPY	3.2
7CQK	ELECTRON MICROSCOPY	3.3
7K0I	ELECTRON MICROSCOPY	3.3
7K0Q	ELECTRON MICROSCOPY	3.3
6M4O	ELECTRON MICROSCOPY	3.4
7K0L	ELECTRON MICROSCOPY	3.4
6M4N	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969W0-F1	93.57	0.88

Functional residue map

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

Catalytic / active sites (1): 28 (within the serine palmitoyltransferase (spt) complex, defines the length of the acyl chain-binding pocket, determining the acyl-coa substrate preference)

Mutagenesis-validated functional residues (2):

Position	Phenotype
28	within the serine palmitoyltransferase (spt) complex, leads to a strong decrease in spt catalytic activity with l-serine
59	impaired down-regulation of spt complex activity by ormdl3.

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: 269 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, PAL_PRMT5_TARGETS_UP, GOBP_POLYOL_METABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOID_METABOLIC_PROCESS, CATTTCA_MIR203, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (6): intracellular protein localization (GO:0008104), 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 (GO:0005783), endoplasmic reticulum membrane (GO:0005789), serine palmitoyltransferase complex (GO:0017059), 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
macromolecule localization	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
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
palmitoyltransferase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPTSSA	SPTLC1	O15269	995
SPTSSA	SPTLC2	O15270	994
SPTSSA	SPTLC3	Q9NUV7	978
SPTSSA	ORMDL1	Q9P0S3	637
SPTSSA	ORMDL2	Q53FV1	632
SPTSSA	B4GALT5	O43286	604
SPTSSA	UGCG	Q16739	578
SPTSSA	TM9SF2	Q99805	567
SPTSSA	KDSR	Q06136	561
SPTSSA	ORMDL3	Q8N138	547
SPTSSA	SPTSSB	Q8NFR3	543
SPTSSA	LAPTM4A	Q15012	501
SPTSSA	ZCCHC9	Q8N567	445
SPTSSA	CERS6	Q6ZMG9	441
SPTSSA	CERS5	Q8N5B7	440

IntAct

29 interactions, top by confidence:

A	B	Type	Score
ORMDL3	SPTLC1	psi-mi:“MI:0915”(physical association)	0.710
SPTLC1	SPTLC2	psi-mi:“MI:0915”(physical association)	0.680
SPTLC1	SPTSSA	psi-mi:“MI:0915”(physical association)	0.570
CYSRT1	SPTSSA	psi-mi:“MI:0915”(physical association)	0.560
RHBDL1	SPTSSA	psi-mi:“MI:0915”(physical association)	0.560
	SPTSSA	psi-mi:“MI:0915”(physical association)	0.560
SPTSSA	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
GET1	SPTSSA	psi-mi:“MI:0915”(physical association)	0.560
SPTLC3	SPTLC1	psi-mi:“MI:0914”(association)	0.480
SPTLC3	SPTSSA	psi-mi:“MI:0915”(physical association)	0.480
SPTLC2	SPTSSA	psi-mi:“MI:0915”(physical association)	0.370
	SPTLC1	psi-mi:“MI:0915”(physical association)	0.320
SPTSSA	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
SPTSSA	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
SPTSSA	RHBDL1	psi-mi:“MI:0915”(physical association)	0.000
SPTSSA		psi-mi:“MI:0915”(physical association)	0.000
SPTSSA	GET1	psi-mi:“MI:0915”(physical association)	0.000
TUBB4A	SPTSSA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): SPTSSA (Synthetic Lethality), SPTSSA (Affinity Capture-RNA), SPTSSA (Affinity Capture-RNA), SPTSSA (PCA), SPTSSA (Two-hybrid), SPTSSA (Two-hybrid), SPTSSA (Two-hybrid), TMEM31 (Two-hybrid), WRB (Two-hybrid), CYSRT1 (Two-hybrid), SPTSSA (Affinity Capture-RNA), SPTSSA (Two-hybrid), SPTSSA (Affinity Capture-RNA), SPTSSA (Two-hybrid), SPTSSA (PCA)

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2505468	NM_138288.4(SPTSSA):c.171_172del (p.Gln58fs)	Pathogenic
2505470	NM_138288.4(SPTSSA):c.152C>T (p.Thr51Ile)	Pathogenic

SpliceAI

822 predictions. Top by Δscore:

Variant	Effect	Δscore
14:34462094:A:AC	donor_gain	1.0000
14:34462095:C:CC	donor_gain	1.0000
14:34435310:T:TC	acceptor_gain	0.9900
14:34461685:A:AC	donor_gain	0.9900
14:34461972:T:TA	donor_gain	0.9900
14:34462099:A:C	donor_gain	0.9900
14:34462105:T:TA	donor_gain	0.9900
14:34462111:C:CA	donor_gain	0.9900
14:34462150:A:AC	donor_gain	0.9900
14:34462151:C:CC	donor_gain	0.9900
14:34435310:T:C	acceptor_gain	0.9800
14:34461686:A:C	donor_gain	0.9800
14:34462177:T:TA	donor_gain	0.9800
14:34435282:C:CT	acceptor_gain	0.9700
14:34435282:C:T	acceptor_gain	0.9700
14:34462120:C:CA	donor_gain	0.9700
14:34451927:T:TA	donor_gain	0.9500
14:34462138:TG:T	donor_gain	0.9500
14:34460286:T:C	donor_gain	0.9400
14:34435305:C:CC	acceptor_gain	0.9300
14:34462098:AACAC:A	donor_gain	0.9300
14:34462095:CTGA:C	donor_gain	0.9200
14:34462095:CTGAA:C	donor_gain	0.9200
14:34462096:TGAA:T	donor_gain	0.9200
14:34462097:GAAC:G	donor_gain	0.9200
14:34462098:AACA:A	donor_gain	0.9200
14:34461965:C:CA	donor_gain	0.9100
14:34435312:G:C	acceptor_gain	0.9000
14:34460239:A:T	donor_gain	0.9000
14:34462090:GGATA:G	donor_loss	0.9000

AlphaMissense

461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:34435252:G:C	F55L	0.998
14:34435252:G:T	F55L	0.998
14:34435254:A:G	F55L	0.998
14:34435262:C:T	G52E	0.996
14:34435263:C:G	G52R	0.996
14:34435263:C:T	G52R	0.996
14:34435281:C:G	G46R	0.996
14:34435281:C:T	G46R	0.996
14:34462114:A:G	W32R	0.996
14:34462114:A:T	W32R	0.996
14:34435280:C:T	G46E	0.994
14:34462110:T:A	E33V	0.994
14:34435253:A:G	F55S	0.993
14:34435274:G:T	A48E	0.993
14:34462109:C:A	E33D	0.993
14:34462109:C:G	E33D	0.993
14:34435229:A:T	I63K	0.992
14:34435254:A:T	F55I	0.992
14:34435276:C:A	M47I	0.992
14:34435276:C:G	M47I	0.992
14:34435276:C:T	M47I	0.992
14:34435303:A:C	N38K	0.992
14:34435303:A:T	N38K	0.992
14:34462111:C:T	E33K	0.990
14:34462122:A:G	L29P	0.990
14:34435269:A:C	Y50D	0.989
14:34462107:C:G	R34P	0.989
14:34462110:T:G	E33A	0.989
14:34435277:A:C	M47R	0.988
14:34435277:A:T	M47K	0.988

dbSNP variants (sampled 300 via entrez): RS1000010823 (14:34443018 T>G), RS1000085645 (14:34463211 G>A,T), RS1000164149 (14:34441007 T>C), RS1000589732 (14:34452030 T>TC), RS1000798163 (14:34446698 A>G), RS1000847046 (14:34449342 T>C), RS1000895931 (14:34455286 C>T), RS1000947633 (14:34455018 C>A,T), RS1001037100 (14:34458509 T>A), RS1001299028 (14:34449082 G>A), RS1001411534 (14:34436164 T>C), RS1001442418 (14:34435035 C>T), RS1001501648 (14:34453728 C>T), RS1001550073 (14:34460503 A>C), RS1001556445 (14:34461215 T>C)

Disease associations

OMIM: gene MIM:613540 | disease phenotypes: MIM:620417, MIM:620416

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic paraplegia 90A, autosomal dominant	Strong	Autosomal dominant
spastic paraplegia 90B, autosomal recessive	Limited	Unknown

Mondo (2): spastic paraplegia 90B, autosomal recessive (MONDO:0957309), spastic paraplegia 90A, autosomal dominant (MONDO:0957308)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000256	Macrocephaly
HP:0000407	Sensorineural hearing impairment
HP:0000545	Myopia
HP:0000750	Delayed speech and language development
HP:0001052	Nevus flammeus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002064	Spastic gait
HP:0002144	Tethered cord
HP:0002307	Drooling
HP:0002360	Sleep disturbance
HP:0002650	Scoliosis
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0008936	Axial hypotonia
HP:0031936	Delayed ability to walk
HP:0034353	Appendicular spasticity
HP:0034392	Joint contracture

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002112_10	Celiac disease	4.000000e-06
GCST006412_85	Intraocular pressure	2.000000e-09
GCST009725_91	Intraocular pressure	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

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: enzyme — Serine palmitoyltransferase

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Air Pollutants	decreases expression, increases abundance	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
cupric chloride	decreases expression	1
resorcinol	increases expression	1
dimethylarsinous acid	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Etoposide	affects response to substance	1
Formaldehyde	increases expression	1
Ketoconazole	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Progesterone	increases expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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