CERT1

ceramide transporter 1, the group of StAR related lipid transfer domain containing|Pleckstrin homology domain containing

Basic information

Region (hg38): 5:75356344-75512138

Previous symbols: [ "COL4A3BP" ]

Links

ENSG00000113163 ∙ NCBI:10087 ∙ OMIM:604677 ∙ HGNC:2205 ∙ Uniprot:Q9Y5P4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 34 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 34	AD	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	Craniofacial; Neurologic	25533962

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CERT1 gene.

• not provided (87 variants)
• Intellectual disability, autosomal dominant 34 (16 variants)
• Inborn genetic diseases (10 variants)
• not specified (6 variants)
• COL4A3BP-Related Disorder (1 variants)
• Limb-girdle muscular dystrophy (1 variants)
• Microcephaly;Neurodevelopmental abnormality;Spastic paraparesis (1 variants)
• - (1 variants)
• Muscular dystrophy, limb-girdle, autosomal recessive 28 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CERT1 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				18	2	20
missense	1	5	41	8		55
nonsense						0
start loss						0
frameshift			1			1
inframe indel	1					1
splice donor/acceptor (+/-2bp)			1			1
splice region				6	2	8
non coding	2		18	8	2	30
Total	4	5	61	34	4

Variants in CERT1

This is a list of pathogenic ClinVar variants found in the CERT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-75356949-G-A			Likely benign (Feb 01, 2023)
5-75357012-C-T			Likely benign (Nov 01, 2023)
5-75359247-C-T		HMGCR-related disorder	Likely benign (Feb 21, 2019)
5-75359287-G-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
5-75359474-A-G		Muscular dystrophy, limb-girdle, autosomal recessive 28	Pathogenic (Jun 21, 2023)
5-75359626-C-T		Statins, attenuated cholesterol lowering by	drug response (Nov 01, 2022)
5-75359673-T-G		-	no classification for the single variant (-)
5-75359992-G-A		Muscular dystrophy, limb-girdle, autosomal recessive 28 • Limb-girdle muscular dystrophy	Pathogenic (Dec 03, 2022)
5-75360119-A-C		Inborn genetic diseases	Uncertain significance (Oct 31, 2022)
5-75360350-G-A		HMGCR-related disorder	Benign (Nov 25, 2019)
5-75360714-T-C		Statins, attenuated cholesterol lowering by	drug response (Nov 01, 2022)
5-75362479-A-G		Statins, attenuated cholesterol lowering by	drug response (Nov 01, 2022)
5-75374046-T-C			Likely benign (Aug 01, 2022)
5-75374136-C-CT			Likely benign (Apr 01, 2024)
5-75374198-G-A			Benign (Sep 01, 2022)
5-75374198-GA-G		not specified	Benign/Likely benign (-)
5-75379360-G-A		Inborn genetic diseases	Uncertain significance (Aug 24, 2020)
5-75379388-A-G			Likely benign (Apr 01, 2023)
5-75379398-C-A			Uncertain significance (Nov 06, 2019)
5-75379398-C-G		COL4A3BP-related disorder	not provided (-)
5-75379421-T-C			Benign/Likely benign (Feb 01, 2023)
5-75379450-C-A			Uncertain significance (Dec 13, 2022)
5-75379477-C-T			Likely benign (Jun 05, 2018)
5-75381076-A-G			Likely benign (Mar 29, 2018)
5-75381086-G-A			Uncertain significance (Jan 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CERT1	protein_coding	protein_coding	ENST00000380494	18	143653

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.667	0.333	125736	0	10	125746	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	272	406	0.670	0.0000204	4899
Missense in Polyphen		52	132.93	0.39119		1620
Synonymous	-1.79	175	147	1.19	0.00000733	1458
Loss of Function	4.81	9	43.1	0.209	0.00000229	496

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000876	0.0000876
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000514	0.0000462
European (Non-Finnish)	0.0000463	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner. {ECO:0000269|PubMed:14685229, ECO:0000269|PubMed:17591919, ECO:0000269|PubMed:18184806, ECO:0000269|PubMed:20036255}.
• Disease: DISEASE: Mental retardation, autosomal dominant 34 (MRD34) [MIM:616351]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:25533962}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sphingolipid Metabolism;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.0962

Intolerance Scores

• loftool: 0.197
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.75

Haploinsufficiency Scores

• pHI: 0.232
• hipred: Y
• hipred_score: 0.672
• ghis: 0.585

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.879

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col4a3bp
• Phenotype: growth/size/body region phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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); hearing/vestibular/ear phenotype; 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); limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: col4a3bpa
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: cell morphogenesis;in utero embryonic development;heart morphogenesis;ceramide metabolic process;muscle contraction;immune response;endoplasmic reticulum organization;signal transduction;cell population proliferation;phosphorylation;sphingolipid biosynthetic process;response to endoplasmic reticulum stress;ER to Golgi ceramide transport;ceramide transport;lipid homeostasis;mitochondrion morphogenesis;intermembrane lipid transfer;intermembrane sphingolipid transfer;ceramide 1-phosphate transport
• Cellular component: nucleoplasm;mitochondrion;endoplasmic reticulum membrane;Golgi apparatus;cytosol;membrane;perinuclear region of cytoplasm
• Molecular function: protein binding;lipid binding;kinase activity;phosphatidylinositol-4-phosphate binding;ceramide binding;intermembrane ceramide transfer activity;ceramide 1-phosphate binding;ceramide 1-phosphate transporter activity