PPCS

phosphopantothenoylcysteine synthetase

Basic information

Region (hg38): 1:42456116-42473385

Links

ENSG00000127125 ∙ NCBI:79717 ∙ OMIM:609853 ∙ HGNC:25686 ∙ Uniprot:Q9HAB8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• cardiomyopathy, dilated, 2c (Strong), mode of inheritance: AR
• cardiomyopathy, dilated, 2c (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 2C	AR	Cardiovascular	Individuals have been described as affected by dilated cardiomyopathy, and awareness may allow prompt management (eg, oral pantethine supplementation has been described as beneficial)	Cardiovascular	29754768

ClinVar

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

• not provided (183 variants)
• Inborn genetic diseases (14 variants)
• Cardiomyopathy, dilated, 2c (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPCS 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	58	9	68
missense	1		83	2		86
nonsense			7			7
start loss			3			3
frameshift			6			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	5		7
non coding			1	5	2	8
Total	1	0	102	65	11

Variants in PPCS

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

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

Position	Type	Phenotype	Significance	ClinVar
1-42456566-A-C			Uncertain significance (Jun 12, 2022)
1-42456566-A-G			Uncertain significance (Mar 02, 2022)
1-42456568-G-A			Uncertain significance (Jun 11, 2021)
1-42456569-G-T			Uncertain significance (Jul 31, 2022)
1-42456576-T-C			Uncertain significance (Sep 24, 2021)
1-42456579-A-G			Uncertain significance (Jun 13, 2022)
1-42456581-C-T			Uncertain significance (Feb 08, 2023)
1-42456582-C-T			Uncertain significance (Mar 01, 2023)
1-42456584-G-A			Uncertain significance (Mar 26, 2022)
1-42456587-G-T			Uncertain significance (Feb 09, 2022)
1-42456588-C-T			Uncertain significance (May 18, 2022)
1-42456589-C-G			Likely benign (Dec 19, 2023)
1-42456589-C-T			Likely benign (Dec 14, 2021)
1-42456592-G-A			Likely benign (Aug 10, 2022)
1-42456594-TC-T			Uncertain significance (Aug 27, 2021)
1-42456595-C-T			Likely benign (Jan 17, 2023)
1-42456598-C-T			Likely benign (Aug 08, 2023)
1-42456599-C-G		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
1-42456600-A-G			Uncertain significance (Aug 22, 2021)
1-42456601-G-A		PPCS-related disorder	Benign (Jan 31, 2024)
1-42456602-C-A			Uncertain significance (Jan 16, 2023)
1-42456606-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
1-42456610-T-A			Likely benign (Feb 16, 2023)
1-42456617-C-T			Uncertain significance (Jan 23, 2022)
1-42456622-G-T			Uncertain significance (Aug 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPCS	protein_coding	protein_coding	ENST00000372561	3	17269

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00804	0.936	124753	0	44	124797	0.000176

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.802	144	174	0.829	0.00000838	1955
Missense in Polyphen		51	66.169	0.77075		742
Synonymous	-1.09	86	74.0	1.16	0.00000376	679
Loss of Function	1.65	5	10.9	0.460	6.29e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000767	0.000766
Ashkenazi Jewish	0.000803	0.000795
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000548	0.0000530
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000825	0.000824

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the first step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4'- phosphopantothenate to form 4-phosphopantothenoylcysteine. {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:12906824}.
• Pathway: Pantothenate and CoA biosynthesis - Homo sapiens (human);Pantothenate and CoA Biosynthesis;Coenzyme A biosynthesis;Metabolism;Vitamin B5 (pantothenate) metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;coenzyme A biosynthesis (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.300
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.417
• ghis: 0.405

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0255

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppcs

Gene ontology

• Biological process: coenzyme biosynthetic process;coenzyme A biosynthetic process
• Cellular component: cytosol
• Molecular function: phosphopantothenate--cysteine ligase activity