PPCDC

Chr 15

phosphopantothenoylcysteine decarboxylase

Also known as: MDS018, PPC-DC, coaC

NCBI Gene: 60490 ENSG00000138621 UniProt: Q96CD2 OMIM: 609854

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.38

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.38LOEUF

pLI 0.000

Z-score 0.81

OE 0.70 (0.38–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.43Z-score

OE missense 0.89 (0.76–1.04)

110 obs / 123.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.38–1.38)

0≤0.351.4

Missense OE?0.89 (0.76–1.04)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 6 / 8.6Missense obs/exp: 110 / 123.4Syn Z: 0.94

Background carrier burden — how many people carry a rare variant somewhere in PPCDC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

261 rare PASS variants

Rare truncating (LoF)

1 in 3,000

43 rare PASS variants

Rare synonymous (reference)

1 in 430

92 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPCDC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 3,200
South Asian	~43k	1 in 360	1 in 4,300
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 30,000
European (Finnish)	~27k	1 in 810	≈ 1 in 27,000
Admixed American	~22k	1 in 150	≈ 1 in 7,400
African / African American	~21k	1 in 220	1 in 1,500
East Asian	~20k	1 in 270	1 in 3,300
Ashkenazi Jewish	~13k	1 in 970	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓