CDS1

protein-coding

CDP-diacylglycerol synthase 1

Gene summary

Breakdown products of phosphoinositides are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for signaling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial membrane where it is thought to be involved in the synthesis of phosphatidylglycerol and cardiolipin and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes encoding this enzyme have been identified in humans, one mapping to human chromosome 4q21 and a second to 20p13. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001263.4

Inheritance

—

ClinVar variants

U:49B:3

Top phenotype

CDS1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr4:84,583,127-84,651,334

External References & Databases

Ensembl (ENSG00000163624)

Transcript & Mutation Effects

hg38 • Region Span ~68.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDS1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 41

CDS1-related disorderTotal: 10

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001263.4. 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					1 clinvar	1
missense			44 clinvar	1 clinvar	1 clinvar	46
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	49	1	2	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001263.4	RefSeq	NP_001254.2	13	MANE Select
ENST00000295887.6	Ensembl	ENSP00000295887.5	13	MANE Select
ENST00000511298.1	Ensembl	ENSP00000421316.1	3	Standard
ENST00000891567.1	Ensembl	ENSP00000561626.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cds1	Danio rerio	Structure: intersegmental vessel Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

cds1

Danio rerio

Structure: intersegmental vessel

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycerophospholipid metabolism - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Phospholipid Biosynthesis
Metabolism of lipids
Metabolism

Biological Process

CDP-choline pathway
phosphatidylinositol biosynthetic process
signal transduction
phototransduction
CDP-diacylglycerol biosynthetic process

Molecular Function

diacylglycerol cholinephosphotransferase activity
phosphatidate cytidylyltransferase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295887
Coding exons: 13
Length: 68360
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125741
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.48	170	234	0.727	0.0000109	3005
Missense (PolyPhen)		50	84.492	0.59177		1143
Synonymous	2.06	59	82.8	0.713	0.00000385	863
Loss of Function	2.91	10	26.0	0.385	0.00000118	329

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Provides CDP-diacylglycerol, an important precursor for the synthesis of phosphatidylinositol (PtdIns), phosphatidylglycerol, and cardiolipin. Overexpression may amplify cellular signaling responses from cytokines. May also play an important role in the signal transduction mechanism of retina and neural cells.;

Recessive Scores

pRec: 0.0926

Intolerance Scores

LoFtool: 0.614
RVIS EVS: 0.48
RVIS percentile EVS: 79.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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