MLYCD

malonyl-CoA decarboxylase

Basic information

Region (hg38): 16:83899115-83951445

Links

ENSG00000103150

∙ NCBI:23417 ∙ OMIM:606761 ∙ HGNC:7150 ∙ Uniprot:O95822 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

malonic aciduria (Definitive), mode of inheritance: AR
malonic aciduria (Strong), mode of inheritance: AR
malonic aciduria (Strong), mode of inheritance: AR
malonic aciduria (Supportive), mode of inheritance: AR
malonic aciduria (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Malonyl-CoA decarboxylase deficiency	AR	Biochemical; Cardiovascular	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	Biochemical; Cardiovascular; Neurologic	6145813; 3709568; 8259873; 10417274; 9869665; 10455107; 12955715; 16275149; 20549361; 22104738; 22778304; 31395333

ClinVar

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

Deficiency_of_malonyl-CoA_decarboxylase (564 variants)
Inborn_genetic_diseases (113 variants)
not_provided (47 variants)
not_specified (36 variants)
MLYCD-related_disorder (16 variants)
Intellectual_disability (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MLYCD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012213.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	262 clinvar	6 clinvar	269
missense	2 clinvar	3 clinvar	220 clinvar	20 clinvar	1 clinvar	246
nonsense	18 clinvar	2 clinvar				20
start loss	1	2				3
frameshift	25 clinvar	7 clinvar	1 clinvar			33
splice donor/acceptor (+/-2bp)	3 clinvar	6 clinvar				9
Total	49	20	222	282	7

Highest pathogenic variant AF is 0.000060319

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MLYCD	protein_coding	protein_coding	ENST00000262430	5	17057

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000648	0.980	124764	0	34	124798	0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.76	330	252	1.31	0.0000152	3102
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000122
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000164	0.000159
Middle Eastern	0.00	0.00
South Asian	0.000425	0.000425
Other	0.00	0.00

dbNSFP

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.;
Pathway: beta-Alanine metabolism - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;Malonyl-coa decarboxylase deficiency;Malonic Aciduria;Propanoate Metabolism;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;Metabolism of lipids;Metabolism of proteins;Beta-oxidation of very long chain fatty acids;Peroxisomal lipid metabolism;Metabolism;Peroxisomal protein import;Fatty acid metabolism;Propanoate metabolism;Pyruvate metabolism (Consensus)

Recessive Scores

pRec: 0.178

Haploinsufficiency Scores

pHI: 0.176
hipred: N
hipred_score: 0.112
ghis: 0.514

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.803

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mlycd
Phenotype: homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Gene ontology

Biological process: response to ischemia;acetyl-CoA biosynthetic process;protein targeting to peroxisome;fatty acid biosynthetic process;acyl-CoA metabolic process;regulation of glucose metabolic process;fatty acid oxidation;regulation of fatty acid beta-oxidation;positive regulation of fatty acid oxidation;malonyl-CoA catabolic process
Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;peroxisome;peroxisomal matrix;cytosol
Molecular function: signaling receptor binding;identical protein binding;malonyl-CoA decarboxylase activity