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 (37 variants)
• not provided (2 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.

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			1	237	6	244
missense		1	179	12	2	194
nonsense	15	1				16
start loss	1	2				3
frameshift	21					21
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	5				6
splice region			1	16	2	19
non coding			21	59	28	108
Total	38	9	204	308	36

Highest pathogenic variant AF is 0.0000394

Variants in MLYCD

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

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

Position	Type	Phenotype	Significance	ClinVar
16-83899122-C-A		not specified	Likely benign (Aug 01, 2017)
16-83899134-T-C		Deficiency of malonyl-CoA decarboxylase	Uncertain significance (Jun 14, 2016)
16-83899138-G-A		not specified • Deficiency of malonyl-CoA decarboxylase • MLYCD-related disorder	Benign/Likely benign (Mar 05, 2018)
16-83899139-G-C		not specified	Likely benign (Aug 15, 2017)
16-83899145-A-C		MLYCD-related disorder • Deficiency of malonyl-CoA decarboxylase	Pathogenic/Likely pathogenic (Aug 01, 2023)
16-83899145-A-T		Deficiency of malonyl-CoA decarboxylase	Pathogenic/Likely pathogenic (Sep 03, 2023)
16-83899146-T-C		Deficiency of malonyl-CoA decarboxylase	Pathogenic (Dec 02, 2023)
16-83899151-G-A		Deficiency of malonyl-CoA decarboxylase • Inborn genetic diseases	Uncertain significance (Jan 18, 2023)
16-83899152-G-A		Deficiency of malonyl-CoA decarboxylase	Conflicting classifications of pathogenicity (Jun 20, 2022)
16-83899152-G-T		Deficiency of malonyl-CoA decarboxylase	Uncertain significance (Feb 17, 2022)
16-83899153-C-G		Deficiency of malonyl-CoA decarboxylase	Likely benign (Feb 16, 2023)
16-83899153-C-T		Deficiency of malonyl-CoA decarboxylase	Likely benign (Dec 31, 2023)
16-83899156-C-T		not specified • Deficiency of malonyl-CoA decarboxylase	Likely benign (Sep 21, 2023)
16-83899157-G-A		Deficiency of malonyl-CoA decarboxylase • not specified • MLYCD-related disorder	Conflicting classifications of pathogenicity (Aug 22, 2022)
16-83899157-GGGCCAGGCTTGAC-G		Deficiency of malonyl-CoA decarboxylase	Pathogenic (Sep 19, 2023)
16-83899158-G-C		Deficiency of malonyl-CoA decarboxylase	Uncertain significance (Aug 04, 2023)
16-83899157-G-GGGCCAGGCTTGAC		Deficiency of malonyl-CoA decarboxylase	Pathogenic (Nov 05, 2023)
16-83899162-A-G		Deficiency of malonyl-CoA decarboxylase	Likely benign (Nov 30, 2023)
16-83899165-C-A		Deficiency of malonyl-CoA decarboxylase	Likely benign (Jan 12, 2024)
16-83899165-C-G		Deficiency of malonyl-CoA decarboxylase	Likely benign (Dec 31, 2023)
16-83899168-G-A		Deficiency of malonyl-CoA decarboxylase	Likely benign (Dec 06, 2023)
16-83899171-G-A		Deficiency of malonyl-CoA decarboxylase	Likely benign (Oct 08, 2023)
16-83899171-G-T		Deficiency of malonyl-CoA decarboxylase	Likely benign (Oct 15, 2023)
16-83899174-C-G		Deficiency of malonyl-CoA decarboxylase	Likely benign (Jul 16, 2023)
16-83899174-C-T		Deficiency of malonyl-CoA decarboxylase	Likely benign (Oct 08, 2023)

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