3-methylcrotonyl-CoA carboxylase deficiency: genes and variants
Explore variant evidence for 3-methylcrotonyl-CoA carboxylase deficiency across 2 analyzed proteins (MCCC2, MCCC1). Linked ClinVar records include 30 pathogenic or likely pathogenic variants, 3 variants of uncertain significance and 4 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-21. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to 3-methylcrotonyl-CoA carboxylase deficiency
MCCC2: Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
It partners with MCCC1 to catalyze an essential carboxylation step in mitochondrial leucine catabolism. Biallelic pathogenic variants cause 3-methylcrotonyl-CoA carboxylase deficiency, which can produce hypoglycemia, acidosis, neurologic symptoms, or remain clinically mild.
23 ClinVar pathogenic / likely pathogenic and 4 uncertain variants in MCCC2 have source records linked to 3-methylcrotonyl-CoA carboxylase deficiency. Association strength is not clinical gene validity.
MCCC1: Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
It provides one subunit of mitochondrial methylcrotonyl-CoA carboxylase, an enzyme required for leucine degradation. Biallelic loss-of-function variants cause 3-methylcrotonyl-CoA carboxylase deficiency, with clinical severity ranging from asymptomatic biochemical abnormalities to metabolic decompensation.
7 ClinVar pathogenic / likely pathogenic and 3 uncertain variants in MCCC1 have source records linked to 3-methylcrotonyl-CoA carboxylase deficiency. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to 3-methylcrotonyl-CoA carboxylase deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MCCC1 T465I | 465 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| MCCC2 C167R | 167 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 G352R | 352 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 Q477R | 477 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC1 R66C | 66 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| MCCC1 E288G | 288 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| MCCC1 M325R | 325 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| MCCC1 R385S | 385 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| MCCC1 R444H | 444 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| MCCC2 R155W | 155 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 H190Y | 190 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 R193C | 193 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 G214A | 214 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 A218V | 218 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 V339M | 339 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 L355F | 355 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 N403S | 403 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 V434L | 434 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 G475R | 475 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 Y520S | 520 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 A524T | 524 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 L317F | 317 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC1 I434M | 434 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| MCCC2 E99Q | 99 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 T139I | 139 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 P310R | 310 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 P397A | 397 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 N230D | 230 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 I437V | 437 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| MCCC2 Y169D | 169 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★) |
Which prediction tools work for 3-methylcrotonyl-CoA carboxylase deficiency
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- AlphaMissense: 98 out of 100
- REVEL: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- ESM1b (LLR): 96 out of 100
- SIFT: 96 out of 100
- CATVariant: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 88 out of 100
- phyloP: 78 out of 100
- Pangolin: 63 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SpliceAI: 61 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- 3-methylcrotonyl-CoA carboxylase 2 deficiency also has ClinVar records linked to MCCC2 variants; they fall partly in the same places as the 3-methylcrotonyl-CoA carboxylase deficiency variants (46 pathogenic / likely pathogenic).
- 3-methylcrotonyl-CoA carboxylase 1 deficiency also has ClinVar records linked to MCCC1 variants; they fall mostly in different places as the 3-methylcrotonyl-CoA carboxylase deficiency variants (21 pathogenic / likely pathogenic).
Diseases related to 3-methylcrotonyl-CoA carboxylase deficiency
- 3-methylcrotonyl-CoA carboxylase 2 deficiency, also linked to MCCC2
- 3-methylcrotonyl-CoA carboxylase 1 deficiency, also linked to MCCC1
Frequently asked questions
Which genes have records linked to 3-methylcrotonyl-CoA carboxylase deficiency?
This view contains 2 analyzed proteins: MCCC2, MCCC1. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 30 pathogenic or likely pathogenic variants, 3 variants of uncertain significance and 4 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 138 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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