CERK

Summary

CERK (ceramide kinase, HGNC:19256) is a protein-coding gene on chromosome 22q13.31, encoding Ceramide kinase (Q8TCT0). Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate.

CERK converts ceramide to ceramide 1-phosphate (C1P), a sphingolipid metabolite. Both CERK and C1P have been implicated in various cellular processes, including proliferation, apoptosis, phagocytosis, and inflammation (Kim et al., 2006 [PubMed 16488390]).

Source: NCBI Gene 64781 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 142 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_022766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19256
Approved symbol	CERK
Name	ceramide kinase
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	hCERK, FLJ23239, dA59H18.3, DKFZp434E0211, FLJ21430, KIAA1646, LK4, dA59H18.2
Ensembl gene	ENSG00000100422
Ensembl biotype	protein_coding
OMIM	610307
Entrez	64781

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000216264, ENST00000443629, ENST00000460254, ENST00000471929, ENST00000918417, ENST00000951510, ENST00000951511, ENST00000951512, ENST00000951513

RefSeq mRNA: 1 — MANE Select: NM_022766 NM_022766

CCDS: CCDS14077

Canonical transcript exons

ENST00000216264 — 13 exons

Exon	Start	End
ENSE00000880801	46711086	46711149
ENSE00001183074	46738007	46738252
ENSE00001227137	46684410	46687206
ENSE00003463236	46699313	46699465
ENSE00003464534	46707843	46707988
ENSE00003475510	46689992	46690200
ENSE00003479694	46701636	46701710
ENSE00003569803	46693427	46693503
ENSE00003590121	46695210	46695315
ENSE00003598404	46720086	46720208
ENSE00003601484	46720902	46721015
ENSE00003613499	46712168	46712293
ENSE00003681959	46691572	46691777

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 95.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.4580 / max 431.3695, expressed in 1762 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194618	16.4580	1762

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	95.95	gold quality
pituitary gland	UBERON:0000007	93.56	gold quality
adenohypophysis	UBERON:0002196	93.05	gold quality
granulocyte	CL:0000094	93.00	gold quality
stromal cell of endometrium	CL:0002255	92.72	gold quality
ganglionic eminence	UBERON:0004023	92.36	gold quality
ileal mucosa	UBERON:0000331	92.17	gold quality
heart left ventricle	UBERON:0002084	92.10	gold quality
decidua	UBERON:0002450	91.82	gold quality
cardiac ventricle	UBERON:0002082	91.77	gold quality
pancreas	UBERON:0001264	91.69	gold quality
right atrium auricular region	UBERON:0006631	91.36	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.36	gold quality
cranial nerve II	UBERON:0000941	91.06	gold quality
leukocyte	CL:0000738	91.03	gold quality
monocyte	CL:0000576	90.94	gold quality
mononuclear cell	CL:0000842	90.85	gold quality
blood	UBERON:0000178	90.74	gold quality
apex of heart	UBERON:0002098	90.58	gold quality
cardiac atrium	UBERON:0002081	90.40	gold quality
heart	UBERON:0000948	90.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.25	gold quality
cerebellar cortex	UBERON:0002129	90.19	gold quality
cerebellar hemisphere	UBERON:0002245	90.18	gold quality
cerebellum	UBERON:0002037	89.91	gold quality
body of pancreas	UBERON:0001150	89.86	gold quality
small intestine	UBERON:0002108	89.86	gold quality
periodontal ligament	UBERON:0008266	89.47	gold quality
pancreatic ductal cell	CL:0002079	89.36	silver quality
gall bladder	UBERON:0002110	89.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	11.72
E-ANND-3	yes	4.68
E-ENAD-17	no	42.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, NR2F1, PPARD, RARA

miRNA regulators (miRDB)

96 targeting CERK, 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-4668-3P	100.00	68.74	2635
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716

Literature-anchored findings (GeneRIF, showing 30)

• Molecular cloning and functional characterization (PMID:11956206)
• ceramide kinase and its product, C-1-P, have roles in arachidonic acid release and production of eicosanoids (PMID:12855693)
• CERK translocates during activation from the cytosol to a lipid raft fraction (PMID:15899891)
• Pleckstrin homology domain of CERK is not only indispensable for its activity but also act as a regulator of CERK activity. (PMID:16081073)
• sphingoid chain was also required for substrate recognition by CERK (PMID:16170208)
• Recombinant CERK was analyzed with regard to dependence on divalent cations, to substrate delivery, specificity, and stereoselectivity. CERK associated with the plasma membrane in CHO cells, which is mediated by the N-terminal putative pleckstrin domain. (PMID:16269826)
• CERK-pleckstrin homology domain plays a crucial role in plasma membrane targeting through its binding to phosphatidylinositol 4,5-bisphosphate and subsequent induction of ceramide-1-phosphate production in the vicinity of the membrane. (PMID:16488390)
• These results suggest that ceramide kinase determines the balance between pro-apoptotic ceramide and anti-apoptotic C1P to regulate cell fate, reminiscent of its function in plants. (PMID:17274985)
• Results demonstrate that CERK localizes to areas of eicosanoid synthesis and uses a ceramide “pool” transported in an active manner via CERT. (PMID:17392267)
• HL-60 cells are useful for studying CerK functions in leukocyte differentiation, and they also suggest that CerK might have an important role in such differentiation. (PMID:17957442)
• higher Ca2+ signal observed in hCERK transfected cells as well as the fact that CERK colocalized with EIgG during phagocytosis support hypothesis that Ca2+ signaling is an important factor for increasing phagocytosis and is regulated by CERK (PMID:18156590)
• identification of a cluster of cysteines, C(347)XXXC(351)XXC(354), essential for CerK function (PMID:18662741)
• ceramide kinase, was associated with poor pathohistological grading in breast cancer (PMID:19125296)
• The Pleckstrin Homology (PH) domain of CERK, which is required for Golgi complex localization, can substitute for the N-terminal region of CERKL and allow for wild-type CERKL localization, which is typified by nucleolar accumulation. (PMID:19501188)
• JNK and ceramide kinase govern the biogenesis of lipid droplets through activation of group IVA phospholipase A2 (PMID:19778898)
• We have identified a differential role for ceramide kinase in mast-cell activation (PMID:21255156)
• Expression of hCERK enhanced ceramide-1-phosphate formation and release of arachidonic acid in Ca(2+) ionophore-stimulated cells. (PMID:21621503)
• TNF-alpha exposure of human SH-SY5Y neuroblastoma caused a profound increase in CERK activity. (PMID:22230689)
• Data suggest that inhibition of ceramide kinase (CerK) [by specific gene silencing or pharmacological inhibition] drastically reduced cell proliferation in a neuroblastoma cell line. (PMID:22579669)
• our findings identify a functional role for Cerk in breast cancer recurrence and suggest the clinical utility of agents targeted against this prosurvival pathway. (PMID:25164007)
• an acid sphingomyelinase ceramide kinase pathway in the regulation of the chemokine CCL5 (PMID:29724781)
• results suggest that intracellular ceramide kinase is required for the migration of bone marrow-derived mesenchymal stem cells, and the roles of the intrinsic ceramide kinase in the migration are associated with N-cadherin regulation (PMID:30502084)
• Our study expands the genotypic spectra of CERKL variants, providing insights into the relevant pathogenesis of RP/CRD (PMID:30851774)
• MicroRNA-34a causes ceramide accumulation and effects insulin signaling pathway by targeting ceramide kinase (CERK) in aging skeletal muscle. (PMID:32056304)
• Ceramide Kinase Is Upregulated in Metastatic Breast Cancer Cells and Contributes to Migration and Invasion by Activation of PI 3-Kinase and Akt. (PMID:32092937)
• Inhibitory effects of ceramide kinase on Rac1 activation, lamellipodium formation, cell migration, and metastasis of A549 lung cancer cells. (PMID:32112978)
• Ceramide kinase regulates TNF-alpha-induced immune responses in human monocytic cells. (PMID:33859296)
• Clinical relevance of CERK and SPHK1 in breast cancer and their association with metastasis and drug resistance. (PMID:36309544)
• Ceramide kinase confers tamoxifen resistance in estrogen receptor-positive breast cancer by altering sphingolipid metabolism. (PMID:36410675)
• Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2. (PMID:38556546)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cerk	ENSDARG00000069169
mus_musculus	Cerk	ENSMUSG00000035891
rattus_norvegicus	Cerk	ENSRNOG00000017022
drosophila_melanogaster	Sk1	FBGN0030300
drosophila_melanogaster	Cerk	FBGN0037315
drosophila_melanogaster	Sk2	FBGN0052484
caenorhabditis_elegans		WBGENE00007918
caenorhabditis_elegans	cerk-1	WBGENE00020398

Paralogs (4): AGK (ENSG00000006530), SPHK2 (ENSG00000063176), SPHK1 (ENSG00000176170), CERKL (ENSG00000188452)

Protein

Protein identifiers

Ceramide kinase — Q8TCT0 (reviewed: Q8TCT0)

Alternative names: Acylsphingosine kinase, Lipid kinase 4

All UniProt accessions (2): Q8TCT0, F8WFD8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate. Acts efficiently on natural and analog ceramides (C6, C8, C16 ceramides, and C8-dihydroceramide), to a lesser extent on C2-ceramide and C6-dihydroceramide, but not on other lipids, such as various sphingosines. Shows a greater preference for D-erythro isomer of ceramides. Binds phosphoinositides.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. High level expression in heart, brain, skeletal muscle, kidney and liver; moderate in peripheral blood leukocytes and thymus; very low in spleen, small intestine, placenta and lung.

Activity regulation. Inhibited by sulfatide. Inhibited by sphinganine, sphingenine, and N,N-Dimethylsphingosine (DMS). Cardiolipin at 0.1 uM significantly increases activity, whereas at concentrations >1 uM has an inhibitory effect.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCT0-1	1	yes
Q8TCT0-2	2

RefSeq proteins (1): NP_073603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR045363	CERK_C	Domain
IPR050187	Lipid_Phosphate_FormReg	Family
IPR057465	CERK_PH	Domain

Pfam: PF00781, PF19280, PF25382

Enzyme classification (BRENDA):

• EC 2.7.1.138 — ceramide kinase (BRENDA: 6 organisms, 113 substrates, 40 inhibitors, 26 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
ATP	0.025–85.6	10
CERAMIDE	0.045–20.9	7
STEAROYLCERAMIDE	0.004–0.009	2
C12-CERAMIDE	0.107	1
N-(6-((7-NITRO-2-1,3-BENZOXADIAZOL-4-YL)AMINO)HE	0.001	1
N-ACETYL-D-ERYTHRO-SPHINGENINE	0.02	1
N-ACETYL-SPHINGENINE	0.022	1
N-HEXANOYL-D-ERYTHRO-SPHINGENINE	0.03	1
N-HEXANOYL-SPHINGENINE	0.03	1

Catalyzed reactions (Rhea), 5 shown:

• an N-acylsphing-4-enine + ATP = an N-acylsphing-4-enine 1-phosphate + ADP + H(+) (RHEA:17929)
• N-(hexanoyl)sphing-4-enine + ATP = N-hexanoylsphing-4-enine 1-phosphate + ADP + H(+) (RHEA:43312)
• N-hexadecanoylsphing-4-enine + ATP = N-(hexadecanoyl)-sphing-4-enine-1-phosphate + ADP + H(+) (RHEA:46340)
• N-(acetyl)-sphing-4-enine + ATP = N-(acetyl)-sphing-4-enine-1-phosphate + ADP + H(+) (RHEA:47904)
• N-hexanoyl-(4R)-hydroxysphinganine + ATP = N-hexanoyl-(4R)-hydroxysphinganine-1-phosphate + ADP + H(+) (RHEA:47916)

UniProt features (22 total): binding site 8, sequence variant 3, mutagenesis site 3, modified residue 2, region of interest 2, chain 1, domain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCT0-F1	88.86	0.74

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): 197 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 304; 310; 502–504; 138–140; 170–174; 195–198; 202; 239–241

Post-translational modifications (2): 340, 408

Mutagenesis-validated functional residues (3):

Position	Phenotype
10	99% decrease in catalytic activity but no effect on substrate affinity.
10	71% decrease in catalytic activity but no effect on substrate affinity.
340	15% decrease in catalytic activity and decreased stability.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9840309	Glycosphingolipid biosynthesis

MSigDB gene sets: 262 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_GLYCOSPHINGOLIPID_BIOSYNTHETIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_METABOLIC_PROCESS, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_SPHINGOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (3): ceramide metabolic process (GO:0006672), glycosphingolipid biosynthetic process (GO:0006688), lipid metabolic process (GO:0006629)

GO Molecular Function (7): magnesium ion binding (GO:0000287), ceramide kinase activity (GO:0001729), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
sphingolipid metabolic process	1
glycosphingolipid metabolic process	1
glycolipid biosynthetic process	1
sphingolipid biosynthetic process	1
primary metabolic process	1
metal ion binding	1
lipid kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CERK	SPTLC1	O15269	815
CERK	SPTLC2	O15270	786
CERK	SPTLC3	Q9NUV7	786
CERK	UGCG	Q16739	783
CERK	DGKA	P23743	778
CERK	ASAH1	Q13510	776
CERK	PLA2G4A	P47712	720
CERK	ASAH2	Q9NR71	714
CERK	CERS6	Q6ZMG9	706
CERK	KDSR	Q06136	700
CERK	SMPD1	P17405	695
CERK	SGMS1	Q86VZ5	688
CERK	CERS2	Q96G23	685
CERK	CERS4	Q9HA82	668
CERK	ACER2	Q5QJU3	665

IntAct

112 interactions, top by confidence:

A	B	Type	Score
TNFRSF9	TNFSF9	psi-mi:“MI:0914”(association)	0.820
CCNDBP1	RPLP0	psi-mi:“MI:0914”(association)	0.800
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
CERK		psi-mi:“MI:0915”(physical association)	0.560
ALAS1	CERK	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	CERK	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	CERK	psi-mi:“MI:0915”(physical association)	0.560
CERK	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CERK	psi-mi:“MI:0915”(physical association)	0.560
CERK	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	CERK	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	CERK	psi-mi:“MI:0915”(physical association)	0.560
CERK	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP11-1	CERK	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-1	CERK	psi-mi:“MI:0915”(physical association)	0.560
KRT34	CERK	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	CERK	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	CERK	psi-mi:“MI:0915”(physical association)	0.560
TRIM42	CERK	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-2	CERK	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (111): CERK (Two-hybrid), CERK (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), CERK (Affinity Capture-MS), CERK (Affinity Capture-MS), CERK (Affinity Capture-MS), CERK (Affinity Capture-MS), CERK (Affinity Capture-MS), BUB1B (Affinity Capture-MS), NR3C1 (Affinity Capture-MS), PRMT1 (Affinity Capture-MS), IK (Affinity Capture-MS), NCBP1 (Affinity Capture-MS), ALDH18A1 (Affinity Capture-MS)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: C0LT23, O14159, O31502, Q18425, Q6B516, Q6USK2, Q8CI15, Q8TCT0, Q91V26, Q9JIA7, Q9LRB0, Q9NRA0, Q9NYA1, F2Y4A3, Q06147, Q12246, Q86KF9, Q8K4Q7, Q8L7L1, O82359, Q7ZYJ3, O34799, Q97QZ6, Q9TZI1, Q10123, Q53H12, Q6D2A2, Q7ZW00, Q9ESW4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CERK	“up-regulates quantity”	“ceramide 1-phosphate(2-)”	“chemical modification”
CERK	“down-regulates quantity”	ceramide	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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
Keratinization	9	10.2×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	100
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
932299	Single allele	Pathogenic
997819	Single allele	Pathogenic

SpliceAI

2439 predictions. Top by Δscore:

Variant	Effect	Δscore
22:46687105:T:A	donor_gain	1.0000
22:46690196:TCAAA:T	acceptor_gain	1.0000
22:46690197:CAAA:C	acceptor_gain	1.0000
22:46690197:CAAAC:C	acceptor_gain	1.0000
22:46690201:C:CC	acceptor_gain	1.0000
22:46690205:C:CT	acceptor_gain	1.0000
22:46690206:A:T	acceptor_gain	1.0000
22:46691567:CTTA:C	donor_loss	1.0000
22:46691568:TTA:T	donor_loss	1.0000
22:46691569:TA:T	donor_loss	1.0000
22:46691570:A:AC	donor_gain	1.0000
22:46691570:A:AT	donor_loss	1.0000
22:46691571:C:CA	donor_loss	1.0000
22:46691571:C:CC	donor_gain	1.0000
22:46691776:CT:C	acceptor_gain	1.0000
22:46691778:C:CC	acceptor_gain	1.0000
22:46691784:C:CT	acceptor_gain	1.0000
22:46691794:C:CT	acceptor_gain	1.0000
22:46693435:T:TA	donor_gain	1.0000
22:46693446:CAGTG:C	donor_gain	1.0000
22:46693501:CAT:C	acceptor_gain	1.0000
22:46699341:C:CT	donor_gain	1.0000
22:46699342:C:CT	donor_gain	1.0000
22:46699356:A:AC	donor_gain	1.0000
22:46699356:ACTGT:A	donor_gain	1.0000
22:46699357:C:CC	donor_gain	1.0000
22:46699357:CTGTC:C	donor_gain	1.0000
22:46699461:GTCCC:G	acceptor_gain	1.0000
22:46699462:TCCC:T	acceptor_gain	1.0000
22:46699463:CCC:C	acceptor_gain	1.0000

AlphaMissense

3518 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:46691645:A:G	L420P	0.998
22:46720208:A:T	V86D	0.997
22:46690038:A:G	W499R	0.996
22:46690038:A:T	W499R	0.996
22:46707977:A:T	V194D	0.996
22:46707983:A:T	V192D	0.996
22:46691741:A:G	F388S	0.995
22:46707968:T:A	D197V	0.995
22:46690184:A:T	V450D	0.994
22:46691736:C:G	A390P	0.994
22:46699435:A:T	V274D	0.994
22:46699448:C:G	D270H	0.994
22:46720122:A:G	W115R	0.994
22:46720122:A:T	W115R	0.994
22:46699384:C:T	G291D	0.993
22:46699465:C:A	G264V	0.993
22:46701636:C:A	G264W	0.993
22:46707843:C:A	G239W	0.993
22:46691645:A:T	L420H	0.992
22:46691740:A:C	F388L	0.992
22:46691740:A:T	F388L	0.992
22:46691742:A:G	F388L	0.992
22:46699356:A:C	S300R	0.992
22:46699356:A:T	S300R	0.992
22:46699358:T:G	S300R	0.992
22:46707969:C:G	D197H	0.992
22:46720907:A:G	F84S	0.992
22:46699376:C:A	G294W	0.991
22:46701710:C:T	G239E	0.991
22:46707851:A:T	I236N	0.991

dbSNP variants (sampled 300 via entrez): RS1000033302 (22:46705994 T>A), RS1000052802 (22:46694670 T>C), RS1000111192 (22:46706248 CAG>C), RS1000124360 (22:46688078 C>T), RS1000150390 (22:46728761 G>A,C,T), RS1000151290 (22:46738549 T>G), RS1000155547 (22:46688212 A>G), RS1000189208 (22:46708512 C>T), RS1000244479 (22:46724633 C>A,T), RS1000331557 (22:46692244 TGG>T), RS1000353102 (22:46699687 G>C,T), RS1000357224 (22:46703615 G>A,T), RS1000368919 (22:46738895 A>G), RS1000407860 (22:46703405 C>T), RS1000466798 (22:46697305 CTTTT>C)

Disease associations

OMIM: gene MIM:610307 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006436_6	Triglyceride levels	7.000000e-15
GCST010081_2	Aseptic loosening in total joint arthroplasty	8.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0010725	aseptic loosening

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1764936 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Ceramide kinase

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

Ligand	Action	Affinity	Parameter
NVP 231	Inhibition	7.9	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects expression, affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
ceramide 1-phosphate	affects abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzene	increases expression	1
Calcium	affects reaction, increases phosphorylation	1
Ceramides	affects reaction, increases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydrogen Peroxide	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1768895	Binding	Inhibition of CERK	Discovery and structure-activity relationship of 3-aminopyrid-2-ones as potent and selective interleukin-2 inducible T-cell kinase (Itk) inhibitors. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2U4	Abcam HEK293T CERK KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders