COASY

Coenzyme A synthase

Basic information

Region (hg38): 17:42561466-42566277

Links

ENSG00000068120 ∙ NCBI:80347 ∙ OMIM:609855 ∙ HGNC:29932 ∙ Uniprot:Q13057 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration with brain iron accumulation 6 (Strong), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 6 (Limited), mode of inheritance: AR
• pontocerebellar hypoplasia, type 12 (Moderate), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 6 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia, type 12 (Limited), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 6 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia, type 12 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration with brain iron accumulation 6; Pontocerebellar hypoplasia, type 12	AR	General	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	Neurologic	24360804; 30089828

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COASY gene.

• Neurodegeneration with brain iron accumulation 6 (222 variants)
• not provided (57 variants)
• Inborn genetic diseases (33 variants)
• not specified (20 variants)
• Neurodegeneration with brain iron accumulation (6 variants)
• Pontocerebellar hypoplasia, type 12 (5 variants)
• See cases (3 variants)
• COASY-related condition (2 variants)
• Lipid storage myopathy (1 variants)
• Pontocerebellar hypoplasia, type 12;Neurodegeneration with brain iron accumulation 6 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COASY gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	54	4	60
missense	1	1	131	3	2	138
nonsense	8					8
start loss						0
frameshift	4	4	1			9
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2				2
splice region		1	4	10	1	16
non coding			5	24	6	35
Total	13	7	142	81	12

Highest pathogenic variant AF is 0.000479

Variants in COASY

This is a list of pathogenic ClinVar variants found in the COASY region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-42561996-C-A			Benign (Jun 23, 2018)
17-42562184-C-G		not specified	Likely benign (Feb 19, 2018)
17-42562228-G-C			Likely benign (Mar 30, 2018)
17-42562388-C-G		not specified	Likely benign (Feb 18, 2016)
17-42562417-G-A			Likely benign (Jan 01, 2024)
17-42562425-G-A		not specified	Uncertain significance (Sep 26, 2023)
17-42562482-C-T		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Mar 26, 2018)
17-42562507-C-T		not specified	Likely benign (Jul 10, 2017)
17-42562618-G-A		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Sep 26, 2019)
17-42562622-C-T		Neurodegeneration with brain iron accumulation 6 • COASY-related disorder	Conflicting classifications of pathogenicity (Jul 01, 2023)
17-42562637-G-T		Neurodegeneration with brain iron accumulation 6	Likely benign (Aug 07, 2020)
17-42562645-T-G			Uncertain significance (Aug 10, 2022)
17-42562647-C-T		not specified • Neurodegeneration with brain iron accumulation 6	Benign (Jan 18, 2024)
17-42562662-C-G		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Aug 09, 2022)
17-42562663-C-T		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Aug 17, 2023)
17-42562674-C-CT		Neurodegeneration with brain iron accumulation 6 • not specified	Conflicting classifications of pathogenicity (Nov 14, 2022)
17-42562676-A-G		Neurodegeneration with brain iron accumulation 6	Likely benign (Apr 12, 2022)
17-42562685-C-T		Neurodegeneration with brain iron accumulation 6	Likely benign (Dec 24, 2021)
17-42562703-C-T		Neurodegeneration with brain iron accumulation 6 • COASY-related disorder	Benign/Likely benign (Jan 19, 2024)
17-42562708-C-T		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Nov 29, 2021)
17-42562709-G-A		Neurodegeneration with brain iron accumulation 6	Likely benign (Apr 18, 2022)
17-42562715-G-A			Likely benign (Dec 18, 2018)
17-42562718-G-A		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Jul 14, 2021)
17-42562731-C-G		Neurodegeneration with brain iron accumulation 6	Uncertain significance (Feb 05, 2022)
17-42562733-C-T		Neurodegeneration with brain iron accumulation 6	Likely benign (Sep 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COASY	protein_coding	protein_coding	ENST00000590958	10	4811

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.09e-10	0.703	125515	0	233	125748	0.000927

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.109	356	362	0.984	0.0000216	3789
Missense in Polyphen		138	143.46	0.96196		1522
Synonymous	0.869	143	157	0.912	0.00000940	1285
Loss of Function	1.44	18	25.9	0.695	0.00000146	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00306	0.00306
Ashkenazi Jewish	0.000601	0.000595
East Asian	0.000326	0.000326
Finnish	0.000370	0.000370
European (Non-Finnish)	0.00116	0.00116
Middle Eastern	0.000326	0.000326
South Asian	0.000560	0.000555
Other	0.00149	0.00147

dbNSFP

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}.
• Pathway: Pantothenate and CoA biosynthesis - Homo sapiens (human);Pantothenate and CoA Biosynthesis;Coenzyme A biosynthesis;Metabolism;Vitamin B5 (pantothenate) metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;coenzyme A biosynthesis (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.510
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.67

Haploinsufficiency Scores

• pHI: 0.0215
• hipred: N
• hipred_score: 0.170
• ghis: 0.544

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.952

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Coasy

Zebrafish Information Network

• Gene name: coasy
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: coenzyme biosynthetic process;coenzyme A biosynthetic process;phosphorylation
• Cellular component: nucleoplasm;mitochondrial outer membrane;mitochondrial matrix;cytosol;extracellular exosome
• Molecular function: dephospho-CoA kinase activity;pantetheine-phosphate adenylyltransferase activity;protein binding;ATP binding