PCYT1A

phosphate cytidylyltransferase 1A, choline

Basic information

Region (hg38): 3:196214222-196287957

Previous symbols: [ "PCYT1" ]

Links

ENSG00000161217 ∙ NCBI:5130 ∙ OMIM:123695 ∙ HGNC:8754 ∙ Uniprot:P49585 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylometaphyseal dysplasia-cone-rod dystrophy syndrome (Definitive), mode of inheritance: AR
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• spondylometaphyseal dysplasia-cone-rod dystrophy syndrome (Supportive), mode of inheritance: AR
• spondylometaphyseal dysplasia-cone-rod dystrophy syndrome (Strong), mode of inheritance: AR
• spondylometaphyseal dysplasia-cone-rod dystrophy syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipodystrophy, congenital generalized, type 5	AR	Cardiovascular; Gastrointestinal; Endocrine	Individuals may be affected by manifestations such as early onset dyslipidemia, hepatic steatosis, and insulin-resistant diabetes mellitus, and awareness may enable early identification and management	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Ophthalmologic	24387990; 24387991; 24889630

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCYT1A gene.

• Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome (6 variants)
• not provided (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCYT1A 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			1	67	4	72
missense	5	2	94	12	2	115
nonsense	2		5			7
start loss						0
frameshift		3	4			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			5	7	1	13
non coding			1	30	9	40
Total	7	5	107	109	15

Highest pathogenic variant AF is 0.0000263

Variants in PCYT1A

This is a list of pathogenic ClinVar variants found in the PCYT1A region.

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

Position	Type	Phenotype	Significance	ClinVar
3-196216707-G-A		SLC51A-related disorder	Likely benign (Jan 11, 2023)
3-196216711-C-T		SLC51A-related disorder	Likely benign (Jul 15, 2024)
3-196216712-G-A		SLC51A-related disorder	Likely benign (May 11, 2023)
3-196216719-C-T		SLC51A-related disorder	Likely benign (Jan 27, 2022)
3-196216720-C-G		not specified	Uncertain significance (Feb 16, 2023)
3-196216721-G-A		SLC51A-related disorder	Likely benign (Jan 31, 2023)
3-196216727-G-C		not specified	Uncertain significance (Apr 13, 2022)
3-196217837-G-A		SLC51A-related disorder	Likely benign (May 01, 2024)
3-196217859-T-C		SLC51A-related disorder	Uncertain significance (Mar 29, 2024)
3-196217881-C-T		SLC51A-related disorder	Likely benign (Feb 27, 2024)
3-196217893-C-T			Benign (Mar 29, 2018)
3-196217927-C-T		SLC51A-related disorder • not specified	Uncertain significance (Dec 14, 2023)
3-196226952-T-TCTC		SLC51A-related disorder	Likely benign (Jan 09, 2024)
3-196226957-T-C		SLC51A-related disorder	Likely benign (Jul 23, 2023)
3-196226961-C-T		SLC51A-related disorder	Likely benign (Feb 22, 2024)
3-196226965-C-A		not specified	Uncertain significance (Oct 25, 2023)
3-196226966-C-T		SLC51A-related disorder	Likely benign (Dec 03, 2021)
3-196226969-G-T		SLC51A-related disorder	Likely benign (Jul 13, 2021)
3-196226982-C-A		not specified	Likely benign (Dec 06, 2021)
3-196227014-G-A		SLC51A-related disorder	Likely benign (Sep 09, 2024)
3-196227048-G-A		not specified	Uncertain significance (Sep 29, 2022)
3-196227088-G-C		not specified	Uncertain significance (Jan 06, 2023)
3-196227100-G-C		not specified	Uncertain significance (Oct 29, 2021)
3-196227109-C-G		SLC51A-related disorder	Uncertain significance (Sep 03, 2024)
3-196227683-G-C		SLC51A-related disorder	Likely benign (May 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCYT1A	protein_coding	protein_coding	ENST00000292823	8	73736

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000202	0.977	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	145	212	0.684	0.0000127	2426
Missense in Polyphen		34	77.384	0.43937		810
Synonymous	-0.520	87	81.0	1.07	0.00000527	677
Loss of Function	2.06	11	21.2	0.518	0.00000142	217

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000227	0.000215
Ashkenazi Jewish	0.000217	0.000198
East Asian	0.000303	0.000272
Finnish	0.000234	0.000231
European (Non-Finnish)	0.000227	0.000211
Middle Eastern	0.000303	0.000272
South Asian	0.000243	0.000229
Other	0.000211	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Controls phosphatidylcholine synthesis.
• Disease: DISEASE: Spondylometaphyseal dysplasia with cone-rod dystrophy (SMDCRD) [MIM:608940]: A disorder characterized by postnatal growth deficiency resulting in profound short stature, rhizomelia with bowing of the lower extremities, platyspondyly with anterior vertebral protrusions, progressive metaphyseal irregularity and cupping with shortened tubular bones, and early-onset progressive visual impairment associated with a pigmentary maculopathy and electroretinographic evidence of cone-rod dysfunction. {ECO:0000269|PubMed:24387990, ECO:0000269|PubMed:24387991}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Phosphonate and phosphinate metabolism - Homo sapiens (human);Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics;Lamivudine Metabolism Pathway;Phospholipid Biosynthesis;Kennedy pathway from Sphingolipids;One carbon metabolism and related pathways;Acetylcholine Synthesis;Metabolism of lipids;phosphatidylcholine biosynthesis;Metabolism;Synthesis of PC;phosphatidylcholine biosynthesis pathway;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Intolerance Scores

• loftool: 0.323
• rvis_EVS: -0.85
• rvis_percentile_EVS: 11.06

Haploinsufficiency Scores

• pHI: 0.755
• hipred: Y
• hipred_score: 0.614
• ghis: 0.597

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0213

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcyt1a
• Phenotype: reproductive system phenotype; 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); 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); hematopoietic system phenotype; respiratory system phenotype; embryo phenotype; immune system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: phosphatidylcholine biosynthetic process;CDP-choline pathway
• Cellular component: nuclear envelope;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;plasma membrane;glycogen granule
• Molecular function: choline-phosphate cytidylyltransferase activity;calmodulin binding;phosphatidylcholine binding;protein homodimerization activity