COASY

Chr 17AR

Coenzyme A synthase

Also known as: DPCK, NBIA6, NBP, PCH12, PPAT, UKR1, pOV-2

NCBI Gene: 80347ENSG00000068120UniProt: Q13057

Coenzyme A (CoA) functions as a carrier of acetyl and acyl groups in cells and thus plays an important role in numerous synthetic and degradative metabolic pathways in all organisms. In eukaryotes, CoA and its derivatives are also involved in membrane trafficking and signal transduction. This gene encodes the bifunctional protein coenzyme A synthase (CoAsy) which carries out the last two steps in the biosynthesis of CoA from pantothenic acid (vitamin B5). The phosphopantetheine adenylyltransferase domain of this bifunctional protein catalyzes the conversion of 4'-phosphopantetheine into dephospho-coenzyme A (dpCoA) while its dephospho-CoA kinase domain completes the final step by phosphorylating dpCoA to form CoA. Mutations in this gene are associated with neurodegeneration with brain iron accumulation (NBIA). Alternative splicing results in multiple isoforms. [provided by RefSeq, Apr 2014]

Primary Disease Associations & Inheritance

Neurodegeneration with brain iron accumulation 6MIM #615643
AR
Pontocerebellar hypoplasia, type 12MIM #618266
AR
408
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COASY
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 202 VUS of 408 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.000
Z-score 1.44
OE 0.70 (0.48–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.11Z-score
OE missense 0.98 (0.90–1.07)
356 obs / 361.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.70 (0.48–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.90–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 18 / 25.9Missense obs/exp: 356 / 361.8Syn Z: 0.87

ClinVar Variant Classifications

408 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic13
VUS202
Likely Benign143
Benign13
Conflicting13
24
Pathogenic
13
Likely Pathogenic
202
VUS
143
Likely Benign
13
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
16
0
24
Likely Pathogenic
9
2
2
0
13
VUS
1
187
12
2
202
Likely Benign
0
3
53
87
143
Benign
0
2
8
3
13
Conflicting
—13
Total171959192408

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COASY · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

COASY-related neurodegeneration with brain iron accumulation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodegeneration with brain iron accumulation 6

MIM #615643

Molecular basis of disorder known

Autosomal recessive

Pontocerebellar hypoplasia, type 12

MIM #618266

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COASY
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neurodegeneration with brain iron accumulation.
Hayflick SJ et al.·Handb Clin Neurol
2018Review
Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis.
Sakuma I et al.·Proc Natl Acad Sci U S A
2025
Progressive brain atrophy and severe neurodevelopmental phenotype in siblings with biallelic COASY variants.
Rosati J et al.·Am J Med Genet A
2023Case report
Neurodegeneration with brain iron accumulation: Insights into the mitochondria dysregulation.
Wang ZB et al.·Biomed Pharmacother
2019Review
COASY related pontocerebellar hypoplasia type 12: A common Indian mutation with expansion of the phenotypic spectrum.
Mishra R et al.·Am J Med Genet A
2022
Consensus clinical management guideline for beta-propeller protein-associated neurodegeneration.
Wilson JL et al.·Dev Med Child Neurol
2021Review
On the complexity of clinical and molecular bases of neurodegeneration with brain iron accumulation.
Tello C et al.·Clin Genet
2018Review
Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA).
Wydrych A et al.·Biochim Biophys Acta Mol Basis Dis
2025Cohort
Emerging variants, unique phenotypes, and transcriptomic signatures: an integrated study of COASY-associated diseases.
Cavestro C et al.·Ann Clin Transl Neurol
2024
Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis.
Pagani F et al.·Mol Med Rep
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools