PCYT2

protein-coding

phosphate cytidylyltransferase 2, ethanolamine

Gene summary

This gene encodes an enzyme that catalyzes the formation of CDP-ethanolamine from CTP and phosphoethanolamine in the Kennedy pathway of phospholipid synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

MANE transcript

NM_002861.5

Inheritance

ClinVar variants

P:11U:71B:14

Top phenotype

Spastic paraplegia 82, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr17:81,900,958-81,911,432

External References & Databases

Ensembl (ENSG00000185813)

Transcript & Mutation Effects

hg38 • Region Span ~10.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic paraplegia 82, autosomal recessiveDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032906

Submitter: G2P

spastic paraplegia 82, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032906

Submitter: PanelApp Australia

spastic paraplegia 82, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032906

Submitter: Labcorp Genetics (formerly Invitae)

spastic paraplegia 82, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032906

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spastic paraplegia 82, autosomal recessiveAR

Manifestation: Neurologic; Ophthalmologic

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: 31637422

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PCYT2 variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 73

not providedTotal: 29

Spastic paraplegia 82, autosomal recessiveTotal: 19

not specifiedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002861.5. 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				10 clinvar	1 clinvar	11
missense	1 clinvar	6 clinvar	70 clinvar	3 clinvar		80
nonsense		2 clinvar				2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	3	8	71	13	1	96

Highest pathogenic variant AF is 0.00013666073

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002861.5	RefSeq	NP_002852.1	13	MANE Select
ENST00000538936.7	Ensembl	ENSP00000439245.3	13	MANE Select
NM_001184917.3	RefSeq	NP_001171846.1	14	Standard
NM_001256433.3	RefSeq	NP_001243362.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycerophospholipid metabolism - Homo sapiens (human)
Phosphonate and phosphinate metabolism - Homo sapiens (human)
Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics
Lamivudine Metabolism Pathway
Kennedy pathway from Sphingolipids

Biological Process

phosphatidylethanolamine biosynthetic process
phospholipid biosynthetic process

Molecular Function

ethanolamine-phosphate cytidylyltransferase activity

Cellular Component

cellular_component
endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000538721
Coding exons: 14
Length: 10500
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125711
p: 0.0000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.73	169	245	0.689	0.0000153	2651
Missense (PolyPhen)		44	87.114	0.50509		798
Synonymous	-0.735	108	98.7	1.09	0.00000658	779
Loss of Function	2.62	9	22.4	0.402	0.00000105	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000087	0.000087	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	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in the biosynthesis of the phospholipid phosphatidylethanolamine. Catalyzes the formation of CDP-ethanolamine.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.133
RVIS EVS: -0.45
RVIS percentile EVS: 24.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.858

Gene Damage Prediction

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