CERS3

ceramide synthase 3, the group of CERS class homeoboxes

Basic information

Region (hg38): 15:100400395-100544995

Previous symbols: [ "LASS3" ]

Links

ENSG00000154227 ∙ NCBI:204219 ∙ OMIM:615276 ∙ HGNC:23752 ∙ Uniprot:Q8IU89 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive congenital ichthyosis 9 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 9 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 9 (Strong), mode of inheritance: AR
• congenital non-bullous ichthyosiform erythroderma (Supportive), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 9 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 9	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	Dermatologic	23549421; 23754960

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CERS3 gene.

• Inborn_genetic_diseases (44 variants)
• not_provided (30 variants)
• Autosomal_recessive_congenital_ichthyosis_9 (14 variants)
• CERS3-related_disorder (5 variants)
• not_specified (4 variants)
• Lamellar_ichthyosis (2 variants)
• Abnormality_of_the_skin (2 variants)
• Prostate_cancer (1 variants)
• Ichthyosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CERS3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001378789.1. 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				4	5	9
missense	4	2	39	13	2	60
nonsense	2	1				3
start loss						0
frameshift	1	4				5
splice donor/acceptor (+/-2bp)		3	1			4
Total	7	10	40	17	7

Highest pathogenic variant AF is 0.0000248499

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CERS3	protein_coding	protein_coding	ENST00000284382	10	144601

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00569	0.993	125733	0	12	125745	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.613	183	208	0.880	0.0000110	2537
Missense in Polyphen		59	75.724	0.77915		952
Synonymous	-0.400	78	73.6	1.06	0.00000412	658
Loss of Function	2.90	8	23.0	0.347	0.00000105	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000715	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has (dihydro)ceramide synthesis activity with relatively broad substrate specificity, but a preference for C18:0 and other middle- to long-chain fatty acyl-CoAs (By similarity). It is crucial for the synthesis of very long-chain ceramides in the epidermis, to maintain epidermal lipid homeostasis and terminal differentiation. {ECO:0000250, ECO:0000269|PubMed:23754960}.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Metabolism of lipids;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.0785

Intolerance Scores

• rvis_EVS: 0.75
• rvis_percentile_EVS: 86.71

Haploinsufficiency Scores

• pHI: 0.0896
• hipred: N
• hipred_score: 0.342
• ghis: 0.416

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: Cers3
• Phenotype: immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;sphingolipid biosynthetic process;keratinocyte differentiation;ceramide biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;nuclear membrane
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;sphingosine N-acyltransferase activity