CERS4

Summary

CERS4 (ceramide synthase 4, HGNC:23747) is a protein-coding gene on chromosome 19p13.2, encoding Ceramide synthase 4 (Q9HA82). Ceramide synthase that catalyzes formation of ceramide from sphinganine and acyl-CoA substrates, with high selectivity toward long and very-long chains (C18:0-C22:0) as acyl donor.

Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Predicted to be located in endoplasmic reticulum membrane.

Source: NCBI Gene 79603 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 116 total
• Druggable target: yes
• MANE Select transcript: NM_024552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23747
Approved symbol	CERS4
Name	ceramide synthase 4
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12089, Trh1
Ensembl gene	ENSG00000090661
Ensembl biotype	protein_coding
OMIM	615334
Entrez	79603

Gene structure

Transcript identifiers

Ensembl transcripts: 100 — 93 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000251363, ENST00000557925, ENST00000558268, ENST00000558302, ENST00000558331, ENST00000558501, ENST00000558877, ENST00000559336, ENST00000559450, ENST00000559490, ENST00000560412, ENST00000561008, ENST00000561053, ENST00000595722, ENST00000599275, ENST00000600912, ENST00000886737, ENST00000886738, ENST00000886739, ENST00000886740, ENST00000886741, ENST00000886742, ENST00000886743, ENST00000886744, ENST00000886745, ENST00000886746, ENST00000886747, ENST00000886748, ENST00000886749, ENST00000886750, ENST00000886751, ENST00000886752, ENST00000886753, ENST00000886754, ENST00000886755, ENST00000886756, ENST00000886757, ENST00000886758, ENST00000886759, ENST00000886760, ENST00000886761, ENST00000886762, ENST00000886763, ENST00000886764, ENST00000886765, ENST00000886766, ENST00000886767, ENST00000886768, ENST00000886769, ENST00000886770, ENST00000886771, ENST00000886772, ENST00000886773, ENST00000886774, ENST00000886775, ENST00000886776, ENST00000886777, ENST00000886778, ENST00000886779, ENST00000913039, ENST00000913040, ENST00000913041, ENST00000913042, ENST00000913043, ENST00000913044, ENST00000913045, ENST00000913046, ENST00000913047, ENST00000913048, ENST00000913049, ENST00000913050, ENST00000913051, ENST00000913052, ENST00000913053, ENST00000913054, ENST00000913055, ENST00000913056, ENST00000913057, ENST00000913058, ENST00000913059, ENST00000913060, ENST00000913061, ENST00000913062, ENST00000913063, ENST00000964421, ENST00000964422, ENST00000964423, ENST00000964424, ENST00000964425, ENST00000964426, ENST00000964427, ENST00000964428, ENST00000964429, ENST00000964430, ENST00000964431, ENST00000964432, ENST00000964433, ENST00000964434, ENST00000964435, ENST00000964436

RefSeq mRNA: 1 — MANE Select: NM_024552 NM_024552

CCDS: CCDS12197

Canonical transcript exons

ENST00000251363 — 12 exons

Exon	Start	End
ENSE00001157184	8251076	8251249
ENSE00001201113	8210706	8210862
ENSE00002558597	8209370	8209494
ENSE00003567630	8254499	8254616
ENSE00003616815	8255607	8255725
ENSE00003638108	8255822	8255879
ENSE00003643765	8256236	8256286
ENSE00003698057	8257879	8257985
ENSE00003699453	8261930	8262421
ENSE00003700132	8256618	8256710
ENSE00003701645	8256949	8257077
ENSE00003702335	8261688	8261844

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1562 / max 116.1511, expressed in 1335 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173645	10.5611	1319
173644	0.2592	136
173647	0.2267	146
173646	0.1092	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.46	gold quality
body of pancreas	UBERON:0001150	97.54	gold quality
right lobe of thyroid gland	UBERON:0001119	96.49	gold quality
left lobe of thyroid gland	UBERON:0001120	95.93	gold quality
right lobe of liver	UBERON:0001114	95.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.62	gold quality
thyroid gland	UBERON:0002046	95.16	gold quality
esophagus mucosa	UBERON:0002469	94.86	gold quality
minor salivary gland	UBERON:0001830	94.76	gold quality
ectocervix	UBERON:0012249	94.62	gold quality
skin of abdomen	UBERON:0001416	94.38	gold quality
skin of leg	UBERON:0001511	93.91	gold quality
sural nerve	UBERON:0015488	93.85	gold quality
endocervix	UBERON:0000458	93.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.34	gold quality
mouth mucosa	UBERON:0003729	93.08	gold quality
nerve	UBERON:0001021	93.05	gold quality
tibial nerve	UBERON:0001323	93.05	gold quality
anterior cingulate cortex	UBERON:0009835	93.03	gold quality
cingulate cortex	UBERON:0003027	92.91	gold quality
spinal cord	UBERON:0002240	92.82	gold quality
cortical plate	UBERON:0005343	92.76	gold quality
right frontal lobe	UBERON:0002810	92.61	gold quality
saliva-secreting gland	UBERON:0001044	92.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.58	gold quality
cerebellar hemisphere	UBERON:0002245	92.44	gold quality
cerebellar cortex	UBERON:0002129	92.33	gold quality
adenohypophysis	UBERON:0002196	92.23	gold quality
esophagus	UBERON:0001043	92.00	gold quality
amygdala	UBERON:0001876	91.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting CERS4, 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-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-6802-3P	97.29	65.42	613
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-339-5P	96.73	66.01	820

Literature-anchored findings (GeneRIF, showing 8)

• The linkage and association of phospholipid transfer protein activity to LASS4 were studied. (PMID:21757428)
• Co-expression of CerS2 with CerS4/CerS6 reversed the inhibitory effect of long chain ceramides on cell proliferation and the induction of apoptosis. we detected no effect on cell proliferation. (PMID:23538298)
• mRNA level of CerS4 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)
• nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5x10-2) (PMID:29738550)
• Ceramide synthase CERS4 gene downregulation is associated with KRAS mutation in colorectal cancer. (PMID:37758931)
• Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer. (PMID:37885013)
• Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD. (PMID:38836837)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cers4b	ENSDARG00000018619
danio_rerio	cers4a	ENSDARG00000031387
mus_musculus	Cers4	ENSMUSG00000008206
rattus_norvegicus	Cers4	ENSRNOG00000001072
drosophila_melanogaster	schlank	FBGN0040918
caenorhabditis_elegans		WBGENE00002043
caenorhabditis_elegans		WBGENE00002044

Paralogs (5): CERS5 (ENSG00000139624), CERS2 (ENSG00000143418), CERS3 (ENSG00000154227), CERS6 (ENSG00000172292), CERS1 (ENSG00000223802)

Protein

Protein identifiers

Ceramide synthase 4 — Q9HA82 (reviewed: Q9HA82)

Alternative names: LAG1 longevity assurance homolog 4, Sphingosine N-acyltransferase CERS4

All UniProt accessions (8): Q9HA82, H0YKC9, H0YKR4, H0YKS3, H0YLY3, H0YMY6, H0YN04, H0YNR6

UniProt curated annotations — full annotation on UniProt →

Function. Ceramide synthase that catalyzes formation of ceramide from sphinganine and acyl-CoA substrates, with high selectivity toward long and very-long chains (C18:0-C22:0) as acyl donor.

Subcellular location. Endoplasmic reticulum membrane.

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

Domain organisation. The last loop motif confers selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) to behenoyl-CoA (docosanoyl-CoA; C22:0-CoA) as acyl donors.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the sphingosine N-acyltransferase family.

RefSeq proteins (1): NP_078828* (*=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)
• EC 2.3.1.297 — very-long-chain ceramide synthase (BRENDA: 7 organisms, 77 substrates, 27 inhibitors, 8 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. 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
D-ERYTHRO-SPHINGANINE	0.0025–0.0032	2
PHYTOSPHINGOSINE	0.0069–0.023	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
BEHENOYL-COA	0.0001	1

Catalyzed reactions (Rhea), 8 shown:

• a fatty acyl-CoA + sphing-4-enine = an N-acylsphing-4-enine + CoA + H(+) (RHEA:23768)
• hexacosanoyl-CoA + sphinganine = N-hexacosanoylsphinganine + CoA + H(+) (RHEA:33351)
• tetracosanoyl-CoA + sphinganine = N-tetracosanoylsphinganine + CoA + H(+) (RHEA:33591)
• docosanoyl-CoA + sphinganine = N-docosanoylsphinganine + CoA + H(+) (RHEA:36535)
• sphinganine + octadecanoyl-CoA = N-(octadecanoyl)-sphinganine + CoA + H(+) (RHEA:36547)
• eicosanoyl-CoA + sphinganine = N-eicosanoylsphinganine + CoA + H(+) (RHEA:36555)
• sphing-4-enine + octadecanoyl-CoA = N-octadecanoylsphing-4-enine + CoA + H(+) (RHEA:36691)
• hexadecasphinganine + octadecanoyl-CoA = N-octadecanoylhexadecasphinganine + CoA + H(+) (RHEA:43044)

UniProt features (24 total): transmembrane region 6, sequence variant 5, modified residue 3, topological domain 2, region of interest 2, mutagenesis site 2, chain 1, short sequence motif 1, glycosylation site 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HA82-F1	85.92	0.63

Functional residue map

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

Post-translational modifications (3): 342, 349, 350

Glycosylation sites (1): 19

Mutagenesis-validated functional residues (2):

Position	Phenotype
291–298	altered specificity toward acyl donor; generates c24 ceramides instead of c18-c22-ceramides.
342–350	decreased phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis

MSigDB gene sets: 154 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_METABOLIC_PROCESS, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_SPHINGOLIPID_BIOSYNTHETIC_PROCESS, ROSS_AML_WITH_PML_RARA_FUSION, GOBP_MEMBRANE_LIPID_METABOLIC_PROCESS

GO Biological Process (4): sphingolipid biosynthetic process (GO:0030148), ceramide biosynthetic process (GO:0046513), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (4): DNA binding (GO:0003677), sphingosine N-acyltransferase activity (GO:0050291), protein binding (GO:0005515), 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
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
binding	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

542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CERS4	GDF1	P27539	883
CERS4	SPTLC3	Q9NUV7	839
CERS4	SPTLC1	O15269	780
CERS4	SPTLC2	O15270	748
CERS4	DEGS2	Q6QHC5	682
CERS4	SGPL1	O95470	676
CERS4	CERK	Q8TCT0	668
CERS4	SMPD2	O60906	663
CERS4	DEGS1	O15121	659
CERS4	UGCG	Q16739	659
CERS4	ASAH1	Q13510	648
CERS4	SMPD1	P17405	636
CERS4	ACER1	Q8TDN7	636
CERS4	ASAH2	Q9NR71	636
CERS4	ACER2	Q5QJU3	635

IntAct

151 interactions, top by confidence:

A	B	Type	Score
PNLIPRP1	CERS4	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	CERS4	psi-mi:“MI:0915”(physical association)	0.560
TEX264	CERS4	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	CERS4	psi-mi:“MI:0915”(physical association)	0.560
EMD	CERS4	psi-mi:“MI:0915”(physical association)	0.560
CTXN3	CERS4	psi-mi:“MI:0915”(physical association)	0.560
VAMP2	CERS4	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	CERS4	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	CERS4	psi-mi:“MI:0915”(physical association)	0.560
	CERS4	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	CERS4	psi-mi:“MI:0915”(physical association)	0.560
FXYD6	CERS4	psi-mi:“MI:0915”(physical association)	0.560
SCD	CERS4	psi-mi:“MI:0915”(physical association)	0.560
CERS4	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
CXCL16	CERS4	psi-mi:“MI:0915”(physical association)	0.560
STX7	CERS4	psi-mi:“MI:0915”(physical association)	0.560
CLEC1A	CERS4	psi-mi:“MI:0915”(physical association)	0.560
MS4A1	CERS4	psi-mi:“MI:0915”(physical association)	0.560
SLC35A1	CERS4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (79): CERS4 (Affinity Capture-MS), CERS4 (Affinity Capture-MS), CERS4 (Proximity Label-MS), CERS4 (Two-hybrid), CERS4 (Two-hybrid), SCD (Two-hybrid), CYB5R3 (Two-hybrid), PLP2 (Two-hybrid), EMD (Two-hybrid), TSPO2 (Two-hybrid), UPK1B (Two-hybrid), IGFBP5 (Two-hybrid), TMEM254 (Two-hybrid), IER3IP1 (Two-hybrid), FXYD6 (Two-hybrid)

ESM2 similar proteins: A1A4P6, A1A5B4, A5PK40, A6NDV4, A6NFX1, A6NGC4, A6QL84, A6QLK4, B1AWJ5, B6ID01, E1BY51, P58749, Q2TA01, Q2YDG0, Q32PG7, Q3T9M1, Q4R7X9, Q5HZE5, Q5JZQ7, Q5R6H1, Q5RBY7, Q60HE8, Q6AY05, Q6AYM9, Q6PHN7, Q6TCG5, Q6UX01, Q6UXD7, Q7RTT9, Q7Z403, Q80ZE4, Q8CE47, Q8R139, Q8TBR7, Q96FZ5, Q96HE8, Q96S97, Q9BSA9, Q9BZW5, Q9CQC4

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

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CSNK2A1	“up-regulates activity”	CERS4	phosphorylation
CERS4	“up-regulates quantity”	ceramide	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2993 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8209494:GGTA:G	donor_loss	1.0000
19:8209495:GT:G	donor_loss	1.0000
19:8254497:A:AG	acceptor_gain	1.0000
19:8254498:G:GG	acceptor_gain	1.0000
19:8254613:GGAG:G	donor_gain	1.0000
19:8254614:GAGG:G	donor_gain	1.0000
19:8254615:AGGT:A	donor_loss	1.0000
19:8254617:GT:G	donor_loss	1.0000
19:8254618:T:G	donor_loss	1.0000
19:8255605:A:AG	acceptor_gain	1.0000
19:8255606:G:GA	acceptor_gain	1.0000
19:8255606:GC:G	acceptor_gain	1.0000
19:8255606:GCC:G	acceptor_gain	1.0000
19:8255606:GCCCC:G	acceptor_gain	1.0000
19:8255708:G:GT	donor_gain	1.0000
19:8255721:GCCAG:G	donor_gain	1.0000
19:8255726:G:GG	donor_gain	1.0000
19:8255820:A:AG	acceptor_gain	1.0000
19:8255821:G:GG	acceptor_gain	1.0000
19:8256614:GCAGA:G	acceptor_loss	1.0000
19:8256615:CA:C	acceptor_loss	1.0000
19:8256616:A:AG	acceptor_gain	1.0000
19:8256617:G:GA	acceptor_loss	1.0000
19:8256617:G:GG	acceptor_gain	1.0000
19:8256889:AG:A	acceptor_gain	1.0000
19:8256890:GG:G	acceptor_gain	1.0000
19:8257073:TGGAG:T	donor_loss	1.0000
19:8257074:GGAGG:G	donor_loss	1.0000
19:8257075:G:GT	donor_gain	1.0000
19:8257076:AGGTG:A	donor_loss	1.0000

AlphaMissense

2563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8257887:G:C	K250N	0.989
19:8257887:G:T	K250N	0.989
19:8257951:T:C	F272L	0.989
19:8257953:C:A	F272L	0.989
19:8257953:C:G	F272L	0.989
19:8256970:C:G	H212D	0.988
19:8257964:G:C	R276P	0.986
19:8255823:T:A	W138R	0.983
19:8255823:T:C	W138R	0.983
19:8256242:T:A	W159R	0.982
19:8256242:T:C	W159R	0.982
19:8256268:G:C	W167C	0.981
19:8256268:G:T	W167C	0.981
19:8261794:T:A	W319R	0.981
19:8261794:T:C	W319R	0.981
19:8256663:T:C	F189L	0.980
19:8256665:C:A	F189L	0.980
19:8256665:C:G	F189L	0.980
19:8251119:T:A	W15R	0.979
19:8251119:T:C	W15R	0.979
19:8257006:T:G	Y224D	0.976
19:8256951:T:A	D205E	0.975
19:8256951:T:G	D205E	0.975
19:8257031:G:A	G232D	0.975
19:8251142:G:C	W22C	0.974
19:8251142:G:T	W22C	0.974
19:8256660:G:C	G188R	0.974
19:8256949:G:C	D205H	0.974
19:8255664:T:A	W117R	0.972
19:8255664:T:C	W117R	0.972

dbSNP variants (sampled 300 via entrez): RS1000032576 (19:8260170 T>C), RS1000034726 (19:8220967 G>A,C,T), RS1000148440 (19:8248310 G>A), RS1000175585 (19:8260837 G>A), RS1000196572 (19:8233872 T>C), RS1000210869 (19:8233219 G>A), RS1000227664 (19:8262604 C>T), RS1000247662 (19:8261038 C>A,T), RS1000261069 (19:8227477 T>A), RS1000334463 (19:8239484 A>C), RS1000334818 (19:8238802 G>A), RS1000346758 (19:8215104 G>A,T), RS1000470748 (19:8244189 A>G), RS1000481447 (19:8233613 T>G), RS1000529434 (19:8236331 T>C)

Disease associations

OMIM: gene MIM:615334 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000493_5	Sphingolipid levels	2.000000e-27
GCST001413_7	Sphingolipid levels	1.000000e-34
GCST002688_6	Very long-chain saturated fatty acid levels (fatty acid 22:0)	4.000000e-26
GCST002688_7	Very long-chain saturated fatty acid levels (fatty acid 22:0)	4.000000e-16
GCST002689_2	Very long-chain saturated fatty acid levels (fatty acid 24:0)	3.000000e-21
GCST002689_3	Very long-chain saturated fatty acid levels (fatty acid 24:0)	1.000000e-17
GCST002690_15	Very long-chain saturated fatty acid levels (fatty acid 20:0)	3.000000e-40
GCST002690_16	Very long-chain saturated fatty acid levels (fatty acid 20:0)	2.000000e-28
GCST005650_11	Serum metabolite ratios in chronic kidney disease	2.000000e-14
GCST005650_12	Serum metabolite ratios in chronic kidney disease	4.000000e-12
GCST005650_13	Serum metabolite ratios in chronic kidney disease	1.000000e-12
GCST005650_14	Serum metabolite ratios in chronic kidney disease	5.000000e-12
GCST005650_15	Serum metabolite ratios in chronic kidney disease	8.000000e-14
GCST005650_16	Serum metabolite ratios in chronic kidney disease	6.000000e-19
GCST005650_173	Serum metabolite ratios in chronic kidney disease	3.000000e-13
GCST006899_7	Thyroid stimulating hormone levels	6.000000e-08
GCST008933_12	Sphingomyelin levels	3.000000e-09
GCST008933_13	Sphingomyelin levels	3.000000e-15
GCST008933_9	Sphingomyelin levels	4.000000e-10
GCST009698_24	Metabolite levels	3.000000e-08
GCST009698_30	Metabolite levels	6.000000e-10
GCST009698_31	Metabolite levels	3.000000e-09
GCST009698_32	Metabolite levels	2.000000e-12
GCST010002_147	Refractive error	4.000000e-16
GCST010653_97	Thyroid stimulating hormone levels	1.000000e-14
GCST012020_52	Serum metabolite levels	9.000000e-27
GCST012020_531	Serum metabolite levels	3.000000e-11
GCST012020_532	Serum metabolite levels	2.000000e-18
GCST012020_533	Serum metabolite levels	3.000000e-12
GCST012020_534	Serum metabolite levels	6.000000e-16

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0010118	sphingomyelin measurement
EFO:1002009	macular telangiectasia type 2
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291570 (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

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
5.16	IC50	7000	nM	CHEMBL5268405

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
(2S)-2-amino-4-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-methylbutan-1-ol	1923494: Inhibition of human CerS4	ic50	7.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Acetaminophen	decreases expression	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases methylation, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, affects methylation	2
FR900359	increases phosphorylation	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	decreases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
kifunensine	increases expression, decreases reaction	1
abrine	decreases expression	1
fatostatin	increases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	affects response to substance	1
Cosmetics	affects cotreatment, increases expression	1
Doxorubicin	decreases 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
CHEMBL5226578	Binding	Inhibition of human CerS4	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.