GeneBe

COASY

protein-coding

Coenzyme A synthase

Gene summary

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]

MANE transcript

NM_025233.7

Inheritance

AR

ClinVar variants

P:45U:194B:98

Top phenotype

Neurodegeneration with brain iron accumulation 6; Pontocerebellar hypoplasia, type 12

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr17:42,561,467-42,566,277

External References & Databases

Ensembl (ENSG00000068120)NCBI Gene (80347)OMIM (609855)HGNC:29932GenCCUniProt (Q13057)AlphaFoldClinVar (COASY)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodegeneration with brain iron accumulation 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014290

Submitter: Labcorp Genetics (formerly Invitae)

neurodegeneration with brain iron accumulation 6DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014290

Submitter: G2P

neurodegeneration with brain iron accumulation 6SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014290

Submitter: Orphanet

neurodegeneration with brain iron accumulation 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014290

Submitter: Genomics England PanelApp

pontocerebellar hypoplasia, type 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032643

Submitter: Labcorp Genetics (formerly Invitae)

neurodegeneration with brain iron accumulation 6LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014290

Submitter: Ambry Genetics

pontocerebellar hypoplasia, type 12LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032643

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodegeneration with brain iron accumulation 6; Pontocerebellar hypoplasia, type 12AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24360804; 30089828Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COASY variants in ClinVar

12 Conditions Cataloged
Neurodegeneration with brain iron accumulation 6Total: 285
not specifiedTotal: 113
not providedTotal: 108
Pontocerebellar hypoplasia, type 12Total: 20
COASY-related disorderTotal: 16
Neurodegeneration with brain iron accumulationTotal: 7
COASY-Related DisordersTotal: 5
See casesTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025233.7. 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
90
clinvar
2
clinvar
 96
missense
1
clinvar
5
clinvar
189
clinvar
5
clinvar
1
clinvar
 201
nonsense
8
clinvar
4
clinvar
 12
start loss
0
frameshift
9
clinvar
12
clinvar
1
clinvar
 22
splice donor/acceptor (+/-2bp)
6
clinvar
 6
Total1827194953337

Highest pathogenic variant AF is 0.0010239995

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_025233.7RefSeqNP_079509.59MANE Select
ENST00000393818.3EnsemblENSP00000377406.19MANE Select
NM_001042529.3RefSeqNP_001035994.19Standard
NM_001042532.4RefSeqNP_001035997.210Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
coasyDanio rerio

Structure: nucleate erythrocyte

Quality: decreased amount

abnormal

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
  • phosphorylation

Molecular Function

  • dephospho-CoA kinase activity
  • pantetheine-phosphate adenylyltransferase activity
  • protein binding
  • ATP binding

Cellular Component

  • nucleoplasm
  • mitochondrial outer membrane
  • mitochondrial matrix
  • cytosol
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000590958
Coding exons
10
Length
4811
Individuals with no LoFs
125515
Homozygous LoFs
0
Heterozygous LoFs
233
Defined
125748
p
0.000927
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1093563620.9840.00002163789
Missense (PolyPhen)138143.460.961961522
Synonymous0.8691431570.9120.000009401285
Loss of Function1.441825.90.6950.00000146268

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00280.0028notable
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish0.000600.00060rare
East Asian0.000330.00033rare
Finnish0.000370.00037rare
European (Non-Finnish)0.00120.0012notable
South Asian0.000560.00056rare
Other0.00150.0015notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Bifunctional enzyme that catalyzes the fourth and fifth sequential steps of CoA biosynthetic pathway. The fourth reaction is catalyzed by the phosphopantetheine adenylyltransferase, coded by the coaD domain; the fifth reaction is catalyzed by the dephospho-CoA kinase, coded by the coaE domain. May act as a point of CoA biosynthesis regulation. {ECO:0000269|PubMed:11923312}.;

Recessive Scores

pRec
0.104

Intolerance Scores

LoFtool
0.510
RVIS EVS
-0.71
RVIS percentile EVS
14.67

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.952

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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