CERT1

protein-coding

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

Gene summary

This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

COL4A3BP

MANE transcript

NM_001379029.1

Inheritance

ClinVar variants

P:13U:141B:55

Top phenotype

Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr5:75,356,345-75,512,138

External References & Databases

Ensembl (ENSG00000113163)

Transcript & Mutation Effects

hg38 • Region Span ~155.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disability, autosomal dominant 34STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014599

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disability, autosomal dominant 34DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014599

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic faciesAD

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 25533962

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CERT1 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 108

Inborn genetic diseasesTotal: 62

not specifiedTotal: 59

Intellectual disability, autosomal dominant 34Total: 27

CERT1-related disorderTotal: 13

COL4A3BP-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001379029.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	36 clinvar		39
missense	2 clinvar	11 clinvar	128 clinvar	19 clinvar		160
nonsense						0
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	2	11	141	55	0	209

Highest pathogenic variant AF is 6.9288643e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001379029.1	RefSeq	NP_001365958.1	17	MANE Select
ENST00000643780.2	Ensembl	ENSP00000495760.1	17	MANE Select
NM_001130105.1	RefSeq	NP_001123577.1	18	Standard
NM_001379002.1	RefSeq	NP_001365931.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
col4a3bpa	Danio rerio	Structure: head Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

col4a3bpa

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sphingolipid Metabolism
Metabolism of lipids
Metabolism
Glycosphingolipid metabolism
Sphingolipid de novo biosynthesis

Biological Process

cell morphogenesis
in utero embryonic development
heart morphogenesis
ceramide metabolic process
muscle contraction

Molecular Function

protein binding
lipid binding
kinase activity
phosphatidylinositol-4-phosphate binding
ceramide binding

Cellular Component

nucleoplasm
mitochondrion
endoplasmic reticulum membrane
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380494
Coding exons: 18
Length: 143653
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125746
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.36	272	406	0.670	0.0000204	4899
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000051	0.000046	rare
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.0962

Intolerance Scores

LoFtool: 0.197
RVIS EVS: -0.6
RVIS percentile EVS: 17.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.879

Gene Damage Prediction

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