CERS1

ceramide synthase 1, the group of CERS class homeoboxes

Basic information

Region (hg38): 19:18868545-18896727

Previous symbols: [ "LASS1" ]

Links

ENSG00000223802 ∙ NCBI:10715 ∙ OMIM:606919 ∙ HGNC:14253 ∙ Uniprot:P27544 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive myoclonic epilepsy type 8 (Limited), mode of inheritance: AR
• progressive myoclonus epilepsy (Moderate), mode of inheritance: AR
• progressive myoclonic epilepsy type 8 (Strong), mode of inheritance: AR
• progressive myoclonic epilepsy type 8 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic 8	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	19243074; 24782409

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CERS1 gene.

• Progressive_myoclonic_epilepsy_type_8 (291 variants)
• not_specified (64 variants)
• not_provided (18 variants)
• CERS1-related_disorder (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CERS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021267.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	105	2	108
missense	1	1	140	5		147
nonsense			2			2
start loss						0
frameshift	1		1			2
splice donor/acceptor (+/-2bp)			2			2
Total	2	1	146	110	2

Highest pathogenic variant AF is 0.000003825901

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CERS1	protein_coding	protein_coding	ENST00000427170	7	28176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		123555	0	7	123562	0.0000283

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.815	137	167	0.822	0.0000107	2206
Missense in Polyphen		39	56.45	0.69088		656
Synonymous	-0.187	75	73.0	1.03	0.00000507	702
Loss of Function	2.35	4	13.2	0.302	5.64e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000115	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000456	0.0000451
Middle Eastern	0.000115	0.000111
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be either a bona fide (dihydro)ceramide synthase or a modulator of its activity. When overexpressed in cells is involved in the production of sphingolipids containing mainly one fatty acid donor (N-linked stearoyl- (C18) ceramide) in a fumonisin B1-independent manner (By similarity). {ECO:0000250|UniProtKB:P27545}.
• Disease: DISEASE: Epilepsy, progressive myoclonic 8 (EPM8) [MIM:616230]: A severe form of progressive myoclonic epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment. {ECO:0000269|PubMed:24782409}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Developmental Biology;Metabolism of lipids;Metabolism;Signaling by NODAL;ceramide <i>de novo</i> biosynthesis;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Intolerance Scores

• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: sphingolipid biosynthetic process;cellular response to drug;cellular response to mycotoxin;ceramide biosynthetic process;negative regulation of telomerase activity;cellular response to UV-A;cellular response to dithiothreitol
• Cellular component: Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: molecular_function;sphingosine N-acyltransferase activity