COASY

Chr 17AR

Coenzyme A synthase

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

Coenzyme A synthase catalyzes the final two steps in coenzyme A biosynthesis from pantothenic acid (vitamin B5), converting 4'-phosphopantetheine to dephospho-coenzyme A and then phosphorylating it to form coenzyme A. Autosomal recessive mutations cause neurodegeneration with brain iron accumulation type 6 and pontocerebellar hypoplasia type 12. The pathogenic mechanism involves disruption of coenzyme A synthesis, which impairs acetyl and acyl group metabolism essential for numerous cellular processes including energy production and membrane trafficking.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.032 OMIM phenotypes
Clinical SummaryCOASY
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 202 VUS of 421 total submissions
📖
GeneReview available — COASY
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.44
OE 0.70 (0.481.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.11Z-score
OE missense 0.98 (0.901.07)
356 obs / 361.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.481.03)
00.351.4
Missense OE0.98 (0.901.07)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 18 / 25.9Missense obs/exp: 356 / 361.8Syn Z: 0.87

ClinVar Variant Classifications

421 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic13
VUS202
Likely Benign144
Benign13
Conflicting13
24
Pathogenic
13
Likely Pathogenic
202
VUS
144
Likely Benign
13
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
7
0
24
Likely Pathogenic
10
2
1
0
13
VUS
1
190
9
2
202
Likely Benign
0
3
53
88
144
Benign
0
2
8
3
13
Conflicting
13
Total271987893409

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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