3-methylcrotonyl-CoA carboxylase 2 deficiency: genes and variants
3-methylcrotonyl-CoA carboxylase 2 deficiency is linked to 1 analyzed protein (MCCC2). 46 DNA variants are known to cause it; 164 more are uncertain, and 4 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to 3-methylcrotonyl-CoA carboxylase 2 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.
46 disease-causing and 164 uncertain variants in MCCC2 are linked to 3-methylcrotonyl-CoA carboxylase 2 deficiency.
Known disease-causing variants in 3-methylcrotonyl-CoA carboxylase 2 deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MCCC2 R155Q | 155 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 A218T | 218 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 R155W | 155 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 H190Y | 190 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 R193H | 193 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 R193C | 193 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 A218V | 218 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 N403T | 403 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 N403S | 403 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 Y520S | 520 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 C167R | 167 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 R268T | 268 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 G352R | 352 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 Q477R | 477 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 G559D | 559 | Disease-causing (★★) | |
| MCCC2 S173L | 173 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 G214A | 214 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 D280Y | 280 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 V434L | 434 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 A524T | 524 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 T556A | 556 | Disease-causing (★★) | |
| MCCC2 I231F | 231 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 E99Q | 99 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 P310R | 310 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 P397A | 397 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 T139I | 139 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 N230D | 230 | CoA carboxyltransferase N-terminal | Disease-causing (★★) |
| MCCC2 I437V | 437 | CoA carboxyltransferase C-terminal | Disease-causing (★★) |
| MCCC2 A218S | 218 | CoA carboxyltransferase N-terminal | Disease-causing (★) |
| MCCC2 P224L | 224 | CoA carboxyltransferase N-terminal | Disease-causing (★) |
| MCCC2 P224T | 224 | CoA carboxyltransferase N-terminal | Disease-causing (★) |
| MCCC2 Y520C | 520 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 T556N | 556 | Disease-causing (★) | |
| MCCC2 L376P | 376 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 R394I | 394 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 Y318C | 318 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 A423D | 423 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 Y23C | 23 | Disease-causing (★) | |
| MCCC2 A156V | 156 | CoA carboxyltransferase N-terminal | Disease-causing (★) |
| MCCC2 Y196H | 196 | CoA carboxyltransferase N-terminal | Disease-causing (★) |
| MCCC2 G237R | 237 | CoA carboxyltransferase N-terminal | Disease-causing (★) |
| MCCC2 V481L | 481 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 T484P | 484 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 A456P | 456 | CoA carboxyltransferase C-terminal | Disease-causing (★) |
| MCCC2 H190R | 190 | CoA carboxyltransferase N-terminal | Disease-causing |
| MCCC2 H266L | 266 | CoA carboxyltransferase N-terminal | Disease-causing |
Uncertain variants in 3-methylcrotonyl-CoA carboxylase 2 deficiency that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| MCCC2 R268G | 268 | CoA carboxyltransferase N-terminal | Uncertain (★) | +7: 2 other pathogenic changes within 3 positions; R268T at the same position is pathogenic; seen in 8.2e-06 of gnomAD DNA copies; REVEL 0.850 |
| MCCC2 V481M | 481 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; V481L at the same position is pathogenic; REVEL 0.930 |
| MCCC2 T556I | 556 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; T556N at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.61 | |
| MCCC2 A524P | 524 | CoA carboxyltransferase C-terminal | Uncertain (★) | +6: in a 3D region that tolerates change poorly (3R); A524T at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.92 |
Same protein, different disease
- Methylcrotonyl-CoA carboxylase deficiency is also caused by MCCC2 variants; they fall in the same places as the 3-methylcrotonyl-CoA carboxylase 2 deficiency variants (23 disease-causing).
Diseases related to 3-methylcrotonyl-CoA carboxylase 2 deficiency
- Methylcrotonyl-CoA carboxylase deficiency, also linked to MCCC2
Frequently asked questions
Which genes are linked to 3-methylcrotonyl-CoA carboxylase 2 deficiency?
In CATVariant, 3-methylcrotonyl-CoA carboxylase 2 deficiency is linked to 1 analyzed protein: MCCC2 (Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial).
How many genetic variants are linked to 3-methylcrotonyl-CoA carboxylase 2 deficiency?
254 variants: 46 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 164 are of uncertain significance or have conflicting reports.
Which uncertain variants in 3-methylcrotonyl-CoA carboxylase 2 deficiency look disease-causing?
4 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example MCCC2 R268G, MCCC2 V481M, MCCC2 T556I and MCCC2 A524P. These are leads for expert review, not diagnoses.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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