MCCC1

methylcrotonyl-CoA carboxylase subunit 1, the group of Methylcrotonyl-CoA carboxylase subunits

Basic information

Region (hg38): 3:183015218-183116075

Links

ENSG00000078070 ∙ NCBI:56922 ∙ OMIM:609010 ∙ HGNC:6936 ∙ Uniprot:Q96RQ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylcrotonyl-CoA carboxylase 1 deficiency (Definitive), mode of inheritance: AR
• 3-methylcrotonyl-CoA carboxylase 1 deficiency (Strong), mode of inheritance: AR
• 3-methylcrotonyl-CoA carboxylase 1 deficiency (Definitive), mode of inheritance: AR
• 3-methylcrotonyl-CoA carboxylase deficiency (Supportive), mode of inheritance: AR
• 3-methylcrotonyl-CoA carboxylase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-Methylcrotonyl-CoA carboxylase 1 deficiency	AR	Biochemical	Therapy may not be necessary/effective in some individuals, but medical (eg, carnitine, glycine) and dietary (eg, low protein, leucine restricted) therapy may be beneficial in some individuals; Precautions in the setting of stressors such as viral illnesses may be beneficial	Biochemical; Neurologic	4194964; 5035417; 1000869; 6441868; 2515383; 1779635; 1517917; 8598648; 9187484; 10485305; 11181649; 11170888; 11893004; 16835865; 17968484; 21734494; 22264772; 22642865; 25356967

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCCC1 gene.

• 3-methylcrotonyl-CoA_carboxylase_1_deficiency (788 variants)
• not_provided (111 variants)
• Inborn_genetic_diseases (80 variants)
• Methylcrotonyl-CoA_carboxylase_deficiency (53 variants)
• not_specified (43 variants)
• MCCC1-related_disorder (37 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCCC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020166.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	202	1	216
missense	4	31	263	17	2	317
nonsense	24	19				43
start loss		2				2
frameshift	37	43	1			81
splice donor/acceptor (+/-2bp)	6	36	1			43
Total	71	131	278	219	3

Highest pathogenic variant AF is 0.00015451774

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCCC1	protein_coding	protein_coding	ENST00000265594	19	100858

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.02e-12	0.920	125659	0	89	125748	0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.543	371	402	0.924	0.0000210	4764
Missense in Polyphen		109	154.72	0.70448		1843
Synonymous	-0.459	151	144	1.05	0.00000844	1375
Loss of Function	2.03	24	37.4	0.641	0.00000175	464

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00103	0.000966
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000380	0.000369
Middle Eastern	0.000326	0.000326
South Asian	0.000500	0.000490
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Biotin-attachment subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3- methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism. {ECO:0000269|PubMed:17360195}.
• Disease: DISEASE: 3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D) [MIM:210200]: An autosomal recessive disorder of leucine catabolism. The phenotype is variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3- hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency. {ECO:0000269|PubMed:11170888, ECO:0000269|PubMed:11181649, ECO:0000269|PubMed:11406611, ECO:0000269|PubMed:16010683, ECO:0000269|PubMed:17968484, ECO:0000269|PubMed:21071250, ECO:0000269|PubMed:22150417, ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865, ECO:0000269|PubMed:25382614, ECO:0000269|PubMed:27601257, ECO:0000269|Ref.6}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Valine, leucine and isoleucine degradation - Homo sapiens (human);3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Amino Acid metabolism;Biotin transport and metabolism;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;leucine degradation;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Valine, leucine and isoleucine degradation;Valine Leucine Isoleucine degradation (Consensus)

Recessive Scores

• pRec: 0.276

Intolerance Scores

• loftool: 0.144
• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.85

Haploinsufficiency Scores

• pHI: 0.330
• hipred: N
• hipred_score: 0.486
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mccc1

Gene ontology

• Biological process: leucine catabolic process;biotin metabolic process;protein heterooligomerization
• Cellular component: 3-methylcrotonyl-CoA carboxylase complex, mitochondrial;mitochondrion;mitochondrial matrix;cytosol;methylcrotonoyl-CoA carboxylase complex
• Molecular function: biotin carboxylase activity;methylcrotonoyl-CoA carboxylase activity;protein binding;ATP binding;biotin binding;metal ion binding