CERS1

ceramide synthase 1, the group of CERS class homeoboxes

Basic information

Region (hg38): 19:18868544-18896727

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 myoclonic epilepsy type 8 (Supportive), mode of inheritance: AR
• progressive myoclonic epilepsy type 8 (Strong), 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 (264 variants)
• not provided (119 variants)
• Inborn genetic diseases (38 variants)
• not specified (14 variants)
• Congenital heart defects, multiple types, 6 (9 variants)
• GDF1-related condition (7 variants)
• Visceral heterotaxy (4 variants)
• Right atrial isomerism (3 variants)
• Right atrial isomerism;Congenital heart defects, multiple types, 6 (2 variants)
• Tetralogy of Fallot (1 variants)
• - (1 variants)
• Heart, malformation of (1 variants)
• GDF1-RELATED DISORDERS (1 variants)
• Double outlet right ventricle (1 variants)
• Heterotaxy (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				82	3	85
missense			119	1		120
nonsense	1		1			2
start loss						0
frameshift			1			1
inframe indel			6			6
splice donor/acceptor (+/-2bp)			1			1
splice region			7	17	2	26
non coding	7	16	74	56	7	160
Total	8	16	202	139	10

Highest pathogenic variant AF is 0.000215

Variants in CERS1

This is a list of pathogenic ClinVar variants found in the CERS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-18868612-C-T			Likely benign (Sep 06, 2019)
19-18868614-C-T		not specified	Uncertain significance (Oct 05, 2023)
19-18868620-C-A		not specified	Uncertain significance (Dec 08, 2021)
19-18868621-C-T			Likely benign (Aug 27, 2022)
19-18868623-CCAT-C		Right atrial isomerism	Pathogenic (Apr 18, 2018)
19-18868624-C-T			Likely pathogenic (Apr 02, 2021)
19-18868625-A-G		Congenital heart defects, multiple types, 6 • Heart, malformation of	Pathogenic/Likely pathogenic (Sep 08, 2023)
19-18868641-G-A			Uncertain significance (Oct 13, 2022)
19-18868664-T-TCAAAGAAGAGCA			Uncertain significance (May 11, 2020)
19-18868665-CAAAG-C		Congenital heart defects, multiple types, 6	Pathogenic/Likely pathogenic (Jan 25, 2023)
19-18868666-AAAG-A		Visceral heterotaxy • Progressive myoclonic epilepsy type 8	Uncertain significance (Aug 31, 2021)
19-18868673-A-G			Uncertain significance (Jul 28, 2023)
19-18868675-C-A		GDF1-related disorder	Likely benign (May 29, 2022)
19-18868678-G-A			Likely benign (Apr 02, 2018)
19-18868681-G-A			Likely benign (Feb 23, 2023)
19-18868686-G-A			Uncertain significance (Sep 01, 2021)
19-18868687-C-T		Progressive myoclonic epilepsy type 8	Likely benign (Jul 10, 2018)
19-18868688-G-C			Uncertain significance (Aug 08, 2019)
19-18868697-G-C			Uncertain significance (Dec 03, 2020)
19-18868700-G-A		not specified	Uncertain significance (Aug 08, 2022)
19-18868700-G-T			Uncertain significance (Dec 05, 2020)
19-18868708-G-C		-	no classification for the single variant (-)
19-18868715-A-C		not specified	Uncertain significance (Jan 27, 2022)
19-18868719-C-T		Congenital heart defects, multiple types, 6	Uncertain significance (Sep 10, 2018)
19-18868729-C-T			Likely benign (Aug 04, 2023)

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
0.0966	0.896	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

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.318
• ghis: 0.569

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

Mouse Genome Informatics

• Gene name: Cers1
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

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