CERS5

Summary

CERS5 (ceramide synthase 5, HGNC:23749) is a protein-coding gene on chromosome 12q13.12, encoding Ceramide synthase 5 (Q8N5B7). Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA).

This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 91012 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 63 total
• Druggable target: yes
• MANE Select transcript: NM_147190

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23749
Approved symbol	CERS5
Name	ceramide synthase 5
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	Trh4, MGC45411, FLJ25304
Ensembl gene	ENSG00000139624
Ensembl biotype	protein_coding
OMIM	615335
Entrez	91012

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 11 protein_coding, 10 nonsense_mediated_decay, 7 retained_intron, 5 protein_coding_CDS_not_defined

ENST00000317551, ENST00000380189, ENST00000422340, ENST00000438450, ENST00000542320, ENST00000546406, ENST00000546514, ENST00000546676, ENST00000547138, ENST00000547455, ENST00000547787, ENST00000547800, ENST00000547852, ENST00000548930, ENST00000548942, ENST00000549089, ENST00000549389, ENST00000549942, ENST00000550079, ENST00000550258, ENST00000550547, ENST00000550899, ENST00000550919, ENST00000551005, ENST00000551384, ENST00000551697, ENST00000551757, ENST00000553122, ENST00000898651, ENST00000922929, ENST00000922930, ENST00000922931, ENST00000964279

RefSeq mRNA: 7 — MANE Select: NM_147190 NM_001281731, NM_001331069, NM_001331070, NM_001331071, NM_001331072, NM_001331073, NM_147190

CCDS: CCDS61120, CCDS8801

Canonical transcript exons

ENST00000317551 — 10 exons

Exon	Start	End
ENSE00002334890	50167101	50167369
ENSE00002358073	50129289	50130694
ENSE00003638593	50143074	50143204
ENSE00003658050	50143952	50144057
ENSE00003693318	50134546	50134702
ENSE00003696090	50135941	50136069
ENSE00003697710	50137728	50137820
ENSE00003697911	50142053	50142110
ENSE00003697975	50138567	50138617
ENSE00003787133	50135732	50135838

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6296 / max 143.1427, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130897	24.5432	1824
130898	0.0864	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	98.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.92	gold quality
cerebellar cortex	UBERON:0002129	98.90	gold quality
cerebellum	UBERON:0002037	98.42	gold quality
ventricular zone	UBERON:0003053	97.38	gold quality
ganglionic eminence	UBERON:0004023	96.84	gold quality
stromal cell of endometrium	CL:0002255	96.72	gold quality
adenohypophysis	UBERON:0002196	96.71	gold quality
cortical plate	UBERON:0005343	96.60	gold quality
right frontal lobe	UBERON:0002810	96.35	gold quality
nucleus accumbens	UBERON:0001882	96.30	gold quality
hypothalamus	UBERON:0001898	96.06	gold quality
pituitary gland	UBERON:0000007	96.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.75	gold quality
caudate nucleus	UBERON:0001873	95.70	gold quality
anterior cingulate cortex	UBERON:0009835	95.64	gold quality
putamen	UBERON:0001874	95.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.63	gold quality
amygdala	UBERON:0001876	95.25	gold quality
right ovary	UBERON:0002118	95.17	gold quality
granulocyte	CL:0000094	95.07	gold quality
left ovary	UBERON:0002119	95.01	gold quality
body of uterus	UBERON:0009853	94.97	gold quality
ascending aorta	UBERON:0001496	94.78	gold quality
thoracic aorta	UBERON:0001515	94.75	gold quality
descending thoracic aorta	UBERON:0002345	94.71	gold quality
endocervix	UBERON:0000458	94.66	gold quality
tibial nerve	UBERON:0001323	94.63	gold quality
skin of leg	UBERON:0001511	94.60	gold quality
left uterine tube	UBERON:0001303	94.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting CERS5, 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-8485	100.00	77.57	4731
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-5693	99.24	66.67	1106

Literature-anchored findings (GeneRIF, showing 11)

• study identifies LASS5 as a genuine dihydroceramide synthase and demonstrates that mammalian dihydroceramide synthases do not require additional subunits for their activity (PMID:16100120)
• accumulation of C(16)-ceramide in mitochondria formed from the protein kinase C-dependent salvage pathway results at least in part from the action of longevity-assurance homologue 5, and the generated ceramide modulates the p38 cascade via PP1 (PMID:17030510)
• Down-regulation of either acid sphingomyelinase or LASS 5-attenuated ceramide accumulation and H/R-induced Bax translocation to mitochondria. (PMID:18676372)
• Overexpression of CerS5 increased apoptosis in HeLa cells. (PMID:20406683)
• mRNA level of CerS5 is higher in cancerous cell lines and decreases following the induction of apoptosis. (PMID:25779024)
• These results suggest that the phosphorylation of ceramide synthases may be a key regulatory point in the control of the distribution and levels of sphingolipids of various acyl-chain lengths. (PMID:26887952)
• LASS5 interacts with SDHB and synergistically represses p53 and p21 activity. (PMID:27280497)
• Studied the role of ceramide synthase 5 (LASS5 or CERS5) gene in atherosclerosis. Downregulation of LASS5 by siRNA was found to attenuate ceramide production and increase expression of some AMPK target genes in HUVEC. Found that LASS5 was involved in negative regulation of atherosclerosis-related genes, such as AMPK-alpha. (PMID:28424433)
• in p53(wt) colon cancer cells chemosensitivity against oxaliplatin or 5-fluorouracil could be enhanced by downregulation of CerS5 expression leading to reduced autophagy and mitochondrial respiration. (PMID:30059758)
• Identification of CERS5 as a molecular biomarker in pan-cancer through multiple omics integrative analysis. (PMID:38244710)
• Lack of ceramide synthase 5 protects retinal ganglion cells from ocular hypertensive injury. (PMID:39182597)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cers5	ENSDARG00000002365
mus_musculus	Cers5	ENSMUSG00000023021
rattus_norvegicus	Cers5	ENSRNOG00000052990
drosophila_melanogaster	schlank	FBGN0040918
caenorhabditis_elegans		WBGENE00002043
caenorhabditis_elegans		WBGENE00002044

Paralogs (5): CERS4 (ENSG00000090661), CERS2 (ENSG00000143418), CERS3 (ENSG00000154227), CERS6 (ENSG00000172292), CERS1 (ENSG00000223802)

Protein

Protein identifiers

Ceramide synthase 5 — Q8N5B7 (reviewed: Q8N5B7)

Alternative names: LAG1 longevity assurance homolog 5, Sphingoid base N-palmitoyltransferase CERS5, Sphingosine N-acyltransferase CERS5

All UniProt accessions (14): Q8N5B7, B4DQR7, F8VQZ6, F8VSK7, F8VXY1, F8VY42, F8W1K4, F8W1N7, F8W1Z3, H0YHG4, H0YHK2, H0YI10, H0YIG1, Q49AQ3

UniProt curated annotations — full annotation on UniProt →

Function. Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA). Can use other acyl donors, but with less efficiency. N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively. Plays a role in de novo ceramide synthesis and surfactant homeostasis in pulmonary epithelia.

Subunit / interactions. Interacts with PAQR4; the interaction regulates the stability and activity of CERS5 and is inhibited in presence of ceramides.

Subcellular location. Endoplasmic reticulum membrane.

Post-translational modifications. Phosphorylated at the C-terminus by CK2.

Activity regulation. Inhibited by fumonisin B1.

Domain organisation. The last loop motif confers selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) as acyl donor.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the sphingosine N-acyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5B7-1	1	yes
Q8N5B7-2	2

RefSeq proteins (7): NP_001268660, NP_001317998, NP_001317999, NP_001318000, NP_001318001, NP_001318002, NP_671723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR006634	TLC-dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR016439	Lag1/Lac1-like	Family

Pfam: PF00046, PF03798

Enzyme classification (BRENDA):

• EC 2.3.1.24 — sphingosine N-acyltransferase (BRENDA: 14 organisms, 68 substrates, 31 inhibitors, 18 Km, 0 kcat entries)
• EC 2.3.1.291 — sphingoid base N-palmitoyltransferase (BRENDA: 3 organisms, 9 substrates, 1 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SPHINGOSINE	0.0011–0.171	3
PALMITOYL-COA	0.0124–0.141	2
SPHINGANINE	0.023–0.144	2
TETRACOSANOYL-COA	0.0546–0.0629	2
BEHENOYL-COA	0.299	1
HEXANOYL-COA	0.522	1
LAUROYL-COA	0.358	1
OLEOYL-COA	0.18	1
STEAROYL-COA	0.146	1

Catalyzed reactions (Rhea), 9 shown:

• a fatty acyl-CoA + sphing-4-enine = an N-acylsphing-4-enine + CoA + H(+) (RHEA:23768)
• sphinganine + hexadecanoyl-CoA = N-hexadecanoylsphinganine + CoA + H(+) (RHEA:36539)
• sphinganine + octadecanoyl-CoA = N-(octadecanoyl)-sphinganine + CoA + H(+) (RHEA:36547)
• sphinganine + tetradecanoyl-CoA = N-(tetradecanoyl)-sphinganine + CoA + H(+) (RHEA:36571)
• sphinganine + (9Z)-octadecenoyl-CoA = N-(9Z-octadecenoyl)-sphinganine + CoA + H(+) (RHEA:36575)
• 2-hydroxyhexadecanoyl-CoA + sphinganine = N-(2-hydroxyhexadecanoyl)-sphinganine + CoA + H(+) (RHEA:36647)
• sphing-4-enine + hexadecanoyl-CoA = N-hexadecanoylsphing-4-enine + CoA + H(+) (RHEA:36687)
• hexadecasphinganine + hexadecanoyl-CoA = N-hexadecanoylhexadecasphinganine + CoA + H(+) (RHEA:43040)
• a sphingoid base + hexadecanoyl-CoA = an N-hexadecanoyl-sphingoid base + CoA + H(+) (RHEA:61472)

UniProt features (25 total): mutagenesis site 8, transmembrane region 6, topological domain 2, region of interest 2, chain 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, splice variant 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5B7-F1	85.91	0.71

Functional residue map

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

Glycosylation sites (1): 26

Mutagenesis-validated functional residues (8):

Position	Phenotype
26	reduced n-glycosylation.
153–165	does not affect specificity toward acyl donor.
220	strongly decreased ceramide synthase activity.
231	does not affect ceramide synthase activity.
254	strongly decreased ceramide synthase activity.
254	does not affect ceramide synthase activity.
299–309	altered specificity toward acyl donor; generates c22-c24 ceramides instead of c16-ceramide.
350–356	decreased phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis

MSigDB gene sets: 115 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, RNGTGGGC_UNKNOWN, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_METABOLIC_PROCESS, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_SPHINGOLIPID_BIOSYNTHETIC_PROCESS, GOBP_MEMBRANE_LIPID_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_BIOSYNTHETIC_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (5): oligodendrocyte development (GO:0014003), sphingolipid biosynthetic process (GO:0030148), ceramide biosynthetic process (GO:0046513), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (3): DNA binding (GO:0003677), sphingosine N-acyltransferase activity (GO:0050291), transferase activity (GO:0016740)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
glial cell development	1
oligodendrocyte differentiation	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
nucleic acid binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CERS5	GDF1	P27539	796
CERS5	SPTLC1	O15269	775
CERS5	SPTLC2	O15270	735
CERS5	SPTLC3	Q9NUV7	710
CERS5	DEGS1	O15121	675
CERS5	SMPD2	O60906	671
CERS5	UGCG	Q16739	658
CERS5	TLCD3B	Q71RH2	655
CERS5	SMPD1	P17405	653
CERS5	SGPL1	O95470	652
CERS5	CERK	Q8TCT0	644
CERS5	SPHK1	Q9NYA1	636
CERS5	ASAH1	Q13510	634
CERS5	DEGS2	Q6QHC5	632
CERS5	KDSR	Q06136	628

IntAct

53 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
CERS2	ATP5F1B	psi-mi:“MI:0914”(association)	0.640
SDHB	CERS5	psi-mi:“MI:0915”(physical association)	0.600
CERS5	SDHB	psi-mi:“MI:0915”(physical association)	0.600
SDHB	CERS5	psi-mi:“MI:0403”(colocalization)	0.600
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
CCR6	PODXL	psi-mi:“MI:0914”(association)	0.530
VIPR2	C15orf61	psi-mi:“MI:0914”(association)	0.350
FPR2	GPR89A	psi-mi:“MI:0914”(association)	0.350
P2RY12	GPR89A	psi-mi:“MI:0914”(association)	0.350
CERS5	HMGCS1	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
VIPR2	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
PIGN	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Affinity Capture-MS), CERS5 (Proximity Label-MS), CERS5 (Proximity Label-MS), CERS5 (Proximity Label-MS), CERS5 (Proximity Label-MS), CERS5 (Proximity Label-MS)

ESM2 similar proteins: A0PK00, A1L2R7, A2BIE7, A2VE61, A3KNK1, A6QPF8, A7XZ53, A8DZH4, B1AZA5, D3ZEH5, D3ZXD8, E1BD52, O35052, P58749, P98191, Q05B45, Q0VFK3, Q15035, Q17QL9, Q1LY80, Q3TA38, Q3UMR5, Q5EAX9, Q5EAY8, Q5FWV6, Q5HZE2, Q5R7B1, Q5U239, Q5ZMP3, Q63ZG0, Q68EY2, Q6DE21, Q6ZMG9, Q8BXA5, Q8C172, Q8C1E7, Q8CIF6, Q8N5B7, Q8NBJ9, Q8WVP7

Diamond homologs: A6ZSP9, G5ED45, P27545, P38703, P78970, Q3ZBF8, Q6EUN0, Q6NQI8, Q6YWS8, Q7Z139, Q84QC0, Q8IU89, Q8N5B7, Q8W4Y5, Q924Z4, Q96G23, Q9D6J1, Q9LDF2, Q9LJK3, Q9M6A3, P27544, Q1A3B0, Q5E9R6, Q6ZMG9, Q8C172, Q9D6K9, Q9HA82, Q9XWE9, W7LKY5, A6ZZV7, G1UJF5, O59735, P28496, Q8J2Q2, Q15035, Q15629, Q5R7Z3, Q5XI41, Q91V04, Q924Z5

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CSNK2A1	“up-regulates activity”	CERS5	phosphorylation
CERS5	“up-regulates quantity”	ceramide	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (i) signalling events	10	10.3×	3e-06
Class A/1 (Rhodopsin-like receptors)	5	9.8×	6e-03
GPCR ligand binding	5	8.4×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	8	33.0×	4e-08
calcium-mediated signaling	6	20.7×	6e-05
positive regulation of cytosolic calcium ion concentration	7	15.5×	6e-05
chemotaxis	5	12.8×	4e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	10.7×	6e-03
G protein-coupled receptor signaling pathway	9	6.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1639 predictions. Top by Δscore:

Variant	Effect	Δscore
12:50130692:TAC:T	acceptor_gain	1.0000
12:50130692:TACC:T	acceptor_loss	1.0000
12:50130694:CCT:C	acceptor_loss	1.0000
12:50130696:T:A	acceptor_loss	1.0000
12:50130711:C:CT	acceptor_gain	1.0000
12:50130712:A:T	acceptor_gain	1.0000
12:50135727:CTT:C	donor_loss	1.0000
12:50135728:TTAC:T	donor_loss	1.0000
12:50135729:TACCA:T	donor_loss	1.0000
12:50135730:A:AC	donor_gain	1.0000
12:50135730:ACC:A	donor_loss	1.0000
12:50135731:C:CC	donor_gain	1.0000
12:50135731:C:T	donor_loss	1.0000
12:50135835:CTGC:C	acceptor_gain	1.0000
12:50135836:TGC:T	acceptor_gain	1.0000
12:50135837:GCCTG:G	acceptor_loss	1.0000
12:50135839:C:CA	acceptor_loss	1.0000
12:50135839:C:CC	acceptor_gain	1.0000
12:50135840:T:A	acceptor_loss	1.0000
12:50135936:TTTAC:T	donor_loss	1.0000
12:50135937:TTAC:T	donor_loss	1.0000
12:50135938:TAC:T	donor_loss	1.0000
12:50135939:A:AC	donor_gain	1.0000
12:50135939:A:C	donor_loss	1.0000
12:50135939:ACCT:A	donor_gain	1.0000
12:50135940:C:CA	donor_loss	1.0000
12:50135940:C:CC	donor_gain	1.0000
12:50135940:CCT:C	donor_gain	1.0000
12:50135940:CCTC:C	donor_gain	1.0000
12:50135942:T:TA	donor_gain	1.0000

AlphaMissense

2582 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:50143122:C:G	R129P	0.997
12:50135764:A:C	F280L	0.996
12:50135764:A:T	F280L	0.996
12:50135766:A:G	F280L	0.996
12:50134596:A:G	W327R	0.995
12:50134596:A:T	W327R	0.995
12:50135830:T:A	K258N	0.995
12:50135830:T:G	K258N	0.995
12:50136048:G:C	H220D	0.994
12:50137731:T:A	R211S	0.994
12:50137731:T:G	R211S	0.994
12:50143135:A:G	W125R	0.994
12:50143135:A:T	W125R	0.994
12:50135773:A:C	S277R	0.993
12:50135773:A:T	S277R	0.993
12:50135775:T:G	S277R	0.993
12:50136026:A:G	L227P	0.993
12:50142109:A:G	W146R	0.993
12:50142109:A:T	W146R	0.993
12:50143131:A:G	F126S	0.993
12:50167116:C:A	R61M	0.993
12:50136045:G:C	H221D	0.992
12:50143176:A:G	L111P	0.992
12:50143980:A:T	L92H	0.992
12:50137732:C:G	R211T	0.991
12:50143967:G:C	F96L	0.991
12:50143967:G:T	F96L	0.991
12:50143969:A:G	F96L	0.991
12:50130685:C:G	D347H	0.990
12:50134675:A:C	S300R	0.990

dbSNP variants (sampled 300 via entrez): RS1000002868 (12:50158422 T>C,G), RS1000046868 (12:50135126 G>A), RS1000181253 (12:50141892 A>G,T), RS1000202158 (12:50154684 A>AT), RS1000286327 (12:50163002 C>A), RS1000351158 (12:50169276 G>A), RS1000351806 (12:50148117 A>G), RS1000361787 (12:50148351 T>G), RS1000525606 (12:50165036 A>G), RS1000618970 (12:50164621 T>C), RS1000678764 (12:50155025 T>G), RS1000760579 (12:50130662 G>A), RS1000765799 (12:50162905 C>A,T), RS1000799212 (12:50150137 A>T), RS1000841035 (12:50128818 C>G)

Disease associations

OMIM: gene MIM:615335 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004776_63	Systolic blood pressure	1.000000e-07
GCST006020_27	Diastolic blood pressure	3.000000e-19
GCST006021_12	Systolic blood pressure	1.000000e-14
GCST006023_6	Hypertension	7.000000e-10
GCST006227_12	Diastolic blood pressure	9.000000e-19
GCST006228_11	Systolic blood pressure	9.000000e-15
GCST006229_4	Hypertension	5.000000e-10
GCST006231_50	Mean arterial pressure	1.000000e-07
GCST007293_76	Body fat distribution (arm fat ratio)	4.000000e-07
GCST007294_123	Body fat distribution (trunk fat ratio)	2.000000e-09
GCST007294_2	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007295_152	Body fat distribution (leg fat ratio)	4.000000e-13
GCST011768_16	Schizophrenia	2.000000e-08
GCST90002388_432	Lymphocyte count	4.000000e-09
GCST90020028_978	Hip circumference adjusted for BMI	9.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0004341	body fat distribution
EFO:0004587	lymphocyte count
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291585 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Ceramide synthase

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	3
Cisplatin	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression	2
FR900359	affects phosphorylation	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
quercitrin	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Cidofovir	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Biological Factors	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Clodronic Acid	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ifosfamide	increases expression	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
CHEMBL5226572	Binding	Inhibition of CerS5 (unknown origin) at 10 uM relative to control	Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network. — J Med Chem

Clinical trials (associated diseases)

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