MLYCD

protein-coding

malonyl-CoA decarboxylase

Gene summary

The product of this gene catalyzes the breakdown of malonyl-CoA to acetyl-CoA and carbon dioxide. Malonyl-CoA is an intermediate in fatty acid biosynthesis, and also inhibits the transport of fatty acyl CoAs into mitochondria. Consequently, the encoded protein acts to increase the rate of fatty acid oxidation. It is found in mitochondria, peroxisomes, and the cytoplasm. Mutations in this gene result in malonyl-CoA decarboyxlase deficiency. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012213.3

Inheritance

ClinVar variants

P:73U:244B:307

Top phenotype

Malonyl-CoA decarboxylase deficiency

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr16:83,899,115-83,951,445

External References & Databases

Ensembl (ENSG00000103150)

Transcript & Mutation Effects

hg38 • Region Span ~52.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

malonic aciduriaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009556

Submitter: Labcorp Genetics (formerly Invitae)

malonic aciduriaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009556

Submitter: G2P

malonic aciduriaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009556

Submitter: ClinGen

malonic aciduriaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009556

Submitter: PanelApp Australia

malonic aciduriaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009556

Submitter: Orphanet

Clinical Genomic Database (CGD)

Malonyl-CoA decarboxylase deficiencyAR

Manifestation: Biochemical; Cardiovascular; Neurologic

Intervention: Biochemical; Cardiovascular

Rationale: Dietary measures (low-fat, high-carbohydrate diet, with one report describing benefit from long-chain triglyceride restriction and medium-chain triglyceride supplementation) can normalize urinary organic acid excretion and prevent hypoglycemic episodes; During infectious/febrile illnesses, inpatient care to reduce morbidity and mortalitiy may be beneficial; Surveillance for cardiac manifestations may allow early management, which may be beneficial

Refs: 6145813; 3709568; 8259873; 10417274; 9869665; 10455107; 12955715; 16275149; 20549361; 22104738; 22778304; 31395333

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MLYCD variants in ClinVar

7 Conditions Cataloged

Deficiency of malonyl-CoA decarboxylaseTotal: 585

Inborn genetic diseasesTotal: 125

not specifiedTotal: 66

not providedTotal: 62

MLYCD-related disorderTotal: 22

Intellectual disabilityTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012213.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	282 clinvar	4 clinvar	287
missense	1 clinvar	4 clinvar	240 clinvar	21 clinvar		266
nonsense	18 clinvar	3 clinvar				21
start loss	1 clinvar	2 clinvar				3
frameshift	24 clinvar	9 clinvar				33
splice donor/acceptor (+/-2bp)	4 clinvar	7 clinvar	3 clinvar			14
Total	48	25	244	303	4	624

Highest pathogenic variant AF is 0.00006031899

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012213.3	RefSeq	NP_036345.2	5	MANE Select
ENST00000262430.6	Ensembl	ENSP00000262430.4	5	MANE Select
ENST00000561562.5	Ensembl	ENSP00000484042.1	4	Standard
ENST00000563312.5	Ensembl	ENSP00000477143.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

beta-Alanine metabolism - Homo sapiens (human)
Propanoate metabolism - Homo sapiens (human)
Peroxisome - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
Metformin Pathway, Pharmacodynamic

Biological Process

response to ischemia
acetyl-CoA biosynthetic process
protein targeting to peroxisome
fatty acid biosynthetic process
acyl-CoA metabolic process

Molecular Function

signaling receptor binding
identical protein binding
malonyl-CoA decarboxylase activity

Cellular Component

cytoplasm
mitochondrion
mitochondrial matrix
peroxisome
peroxisomal matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262430
Coding exons: 5
Length: 17057
Individuals with no LoFs: 124764
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 124798
p: 0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.76	330	252	1.31	0.0000152	3102
Missense (PolyPhen)		92	82.179	1.1195		877
Synonymous	-3.92	170	116	1.46	0.00000785	1050
Loss of Function	2.06	8	17.3	0.464	8.35e-7	200

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00042	0.00042	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation. {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:18314420, ECO:0000269|PubMed:23482565}.;
Disease: DISEASE: Malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360]: Autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. {ECO:0000269|PubMed:10417274}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.178

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.803

Gene Damage Prediction

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