PPCDC

protein-coding

phosphopantothenoylcysteine decarboxylase

Gene summary

Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. PPCDC (EC 4.1.1.36), one of the last enzymes in this pathway, converts phosphopantothenoylcysteine to 4-prime-phosphopantetheine (Daugherty et al., 2002 [PubMed 11923312]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_021823.5

Inheritance

ClinVar variants

U:38B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr15:75,023,586-75,117,462

External References & Databases

Ensembl (ENSG00000138621)

Transcript & Mutation Effects

hg38 • Region Span ~93.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dilated cardiomyopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005021

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPCDC variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021823.5. 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				2 clinvar	1 clinvar	3
missense			38 clinvar	1 clinvar		39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	38	3	1	42

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021823.5	RefSeq	NP_068595.3	5	MANE Select
ENST00000342932.8	Ensembl	ENSP00000343190.3	5	MANE Select
NM_001301101.2	RefSeq	NP_001288030.1	4	Standard
NM_001301102.2	RefSeq	NP_001288031.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pantothenate and CoA biosynthesis - Homo sapiens (human)
Pantothenate and CoA Biosynthesis
Coenzyme A biosynthesis
Metabolism
Vitamin B5 (pantothenate) metabolism

Biological Process

coenzyme biosynthetic process
coenzyme A biosynthetic process

Molecular Function

phosphopantothenoylcysteine decarboxylase activity
protein binding
identical protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342932
Coding exons: 5
Length: 93908
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125746
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.430	110	123	0.891	0.00000700	1332
Missense (PolyPhen)		36	45.24	0.79576		451
Synonymous	0.937	41	49.4	0.830	0.00000310	403
Loss of Function	0.811	6	8.56	0.701	3.62e-7	102

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for the biosynthesis of coenzyme A. Catalyzes the decarboxylation of 4-phosphopantothenoylcysteine to form 4'- phosphopantotheine. {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:15581364}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.571
RVIS EVS: -0.12
RVIS percentile EVS: 45.13

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.950

Gene Damage Prediction

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