MCCC2

Summary

MCCC2 (methylcrotonyl-CoA carboxylase subunit 2, HGNC:6937) is a protein-coding gene on chromosome 5q13.2, encoding Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial (Q9HCC0). Carboxyltransferase 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.

This gene encodes the small subunit of 3-methylcrotonyl-CoA carboxylase. This enzyme functions as a heterodimer and catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. Mutations in this gene are associated with 3-Methylcrotonylglycinuria, an autosomal recessive disorder of leucine catabolism. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 64087 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 3-methylcrotonyl-CoA carboxylase deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 943 total — 69 pathogenic, 92 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 36 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 36
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_022132

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6937
Approved symbol	MCCC2
Name	methylcrotonyl-CoA carboxylase subunit 2
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MCCB, MCCCβ
Ensembl gene	ENSG00000131844
Ensembl biotype	protein_coding
OMIM	609014
Entrez	64087

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 27 protein_coding, 17 nonsense_mediated_decay, 14 retained_intron, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000340941

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 3: 3, TSL 5: 1

ENST00000340941, ENST00000505435, ENST00000505787, ENST00000507169, ENST00000509358, ENST00000509539, ENST00000510895, ENST00000512218, ENST00000629193, ENST00000681968, ENST00000681991, ENST00000682045, ENST00000682175, ENST00000682214, ENST00000682231, ENST00000682438, ENST00000682499, ENST00000682541, ENST00000682640, ENST00000682667, ENST00000682687, ENST00000682727, ENST00000682876, ENST00000683098, ENST00000683163, ENST00000683258, ENST00000683339, ENST00000683403, ENST00000683429, ENST00000683665, ENST00000683789, ENST00000683847, ENST00000683882, ENST00000684024, ENST00000684132, ENST00000684254, ENST00000684310, ENST00000684316, ENST00000684473, ENST00000684474, ENST00000684530, ENST00000684652, ENST00000684686, ENST00000888940, ENST00000888941, ENST00000888942, ENST00000888943, ENST00000935385, ENST00000954856, ENST00000984624, ENST00001015640, ENST00001015641, ENST00001015642, ENST00001082691, ENST00001082692, ENST00001082693, ENST00001082694, ENST00001082695, ENST00001082696, ENST00001110147, ENST00001117499, ENST00001138914

RefSeq mRNA: 2 — MANE Select: NM_022132 NM_001363147, NM_022132

CCDS: CCDS34184, CCDS93731

Canonical transcript exons

ENST00000340941 — 17 exons

Exon	Start	End
ENSE00000972093	71641003	71641075
ENSE00001504608	71643819	71643895
ENSE00001690220	71592926	71592992
ENSE00002063117	71587340	71587554
ENSE00003469021	71635151	71635246
ENSE00003504411	71646211	71646277
ENSE00003520225	71649097	71649253
ENSE00003560687	71599659	71599760
ENSE00003561722	71632121	71632185
ENSE00003572580	71602506	71602633
ENSE00003628776	71634943	71635042
ENSE00003640142	71626640	71626753
ENSE00003641376	71604356	71604468
ENSE00003646186	71650069	71650183
ENSE00003673992	71596280	71596364
ENSE00003677817	71652669	71652754
ENSE00004793785	71656743	71658706

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.9792 / max 335.3199, expressed in 1818 samples.

Highest expression (Bgee): ventricle myocardium, adrenal gland cortex, secondary oocyte, adrenal gland, lobe of liver.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MCCC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 36 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	8.9e-39	+0.74	5:71590554:G:C
Brain Cerebellar Hemisphere	eqtl	4.3e-35	+0.71	5:71595072:A:G
Nerve Tibial	eqtl	1.9e-28	+0.29	5:71594043:G:A
Cells Cultured fibroblasts	eqtl	4.1e-24	+0.26	5:71586708:G:A
Muscle Skeletal	eqtl	3.3e-21	-0.24	5:71634682:T:C
Esophagus Gastroesophageal Junction	eqtl	2.3e-20	+0.34	5:71535173:T:C
Skin Not Sun Exposed Suprapubic	eqtl	8.9e-20	+0.33	5:71503682:C:G
Artery Tibial	eqtl	5.5e-18	+0.29	5:71618624:T:G
Colon Sigmoid	eqtl	3.0e-16	+0.29	5:71590554:G:C
Esophagus Muscularis	eqtl	1.1e-15	+0.26	5:71467108:G:A
Artery Aorta	eqtl	2.0e-13	+0.26	5:71596200:GATTAAGT:G
Skin Sun Exposed Lower leg	eqtl	3.3e-12	+0.25	5:71609582:C:T
Muscle Skeletal	sqtl	4.3e-09	-0.36	5:71633683:A:C
Pituitary	eqtl	1.9e-08	+0.28	5:71590554:G:C
Brain Hypothalamus	eqtl	3.8e-08	+0.36	5:71594043:G:A
Brain Caudate basal ganglia	eqtl	7.2e-08	+0.28	5:71590146:C:T
Breast Mammary Tissue	eqtl	7.8e-08	-0.16	5:71467261:A:G
Testis	sqtl	2.2e-06	-0.40	5:71491873:A:G
Adipose Subcutaneous	eqtl	6.4e-06	+0.13	5:71551996:A:G
Brain Frontal Cortex BA9	eqtl	1.6e-05	+0.17	5:71633683:A:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
56873	16.0853	1788
56872	11.9276	1752
56874	3.5111	1445
56871	2.9590	1358
56875	2.2731	999
56876	0.2231	85

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	96.12	gold quality
right adrenal gland cortex	UBERON:0035827	95.81	gold quality
secondary oocyte	CL:0000655	95.67	gold quality
right adrenal gland	UBERON:0001233	95.67	gold quality
right lobe of liver	UBERON:0001114	95.60	gold quality
heart left ventricle	UBERON:0002084	95.58	gold quality
cardiac ventricle	UBERON:0002082	95.48	gold quality
tongue squamous epithelium	UBERON:0006919	95.21	silver quality
left adrenal gland	UBERON:0001234	95.11	gold quality
heart right ventricle	UBERON:0002080	95.11	gold quality
liver	UBERON:0002107	94.82	gold quality
rectum	UBERON:0001052	94.81	gold quality
left adrenal gland cortex	UBERON:0035825	94.68	gold quality
adrenal gland	UBERON:0002369	94.36	gold quality
apex of heart	UBERON:0002098	94.32	gold quality
adrenal cortex	UBERON:0001235	94.24	gold quality
esophagus squamous epithelium	UBERON:0006920	93.98	gold quality
corpus epididymis	UBERON:0004359	93.86	gold quality
ileal mucosa	UBERON:0000331	93.77	gold quality
nephron tubule	UBERON:0001231	93.77	gold quality
epithelium of esophagus	UBERON:0001976	93.77	gold quality
heart	UBERON:0000948	93.57	gold quality
choroid plexus epithelium	UBERON:0003911	93.39	gold quality
gastrocnemius	UBERON:0001388	93.18	gold quality
epithelium of mammary gland	UBERON:0003244	93.14	gold quality
endometrium	UBERON:0001295	93.07	gold quality
mammary duct	UBERON:0001765	92.96	gold quality
muscle of leg	UBERON:0001383	92.95	gold quality
adult mammalian kidney	UBERON:0000082	92.94	gold quality
right atrium auricular region	UBERON:0006631	92.90	gold quality
squamous epithelium	UBERON:0006914	92.77	gold quality
adrenal tissue	UBERON:0018303	92.73	gold quality
kidney	UBERON:0002113	92.68	gold quality
cardiac atrium	UBERON:0002081	92.60	gold quality
hair follicle	UBERON:0002073	92.38	gold quality
body of pancreas	UBERON:0001150	92.31	gold quality
right lobe of thyroid gland	UBERON:0001119	92.29	gold quality
myocardium	UBERON:0002349	92.22	gold quality
cervix squamous epithelium	UBERON:0006922	92.02	silver quality
left lobe of thyroid gland	UBERON:0001120	92.01	gold quality
oocyte	CL:0000023	91.97	gold quality
prostate gland	UBERON:0002367	91.72	gold quality
caput epididymis	UBERON:0004358	91.70	gold quality
thyroid gland	UBERON:0002046	91.67	gold quality
calcaneal tendon	UBERON:0003701	91.49	gold quality
kidney epithelium	UBERON:0004819	91.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.40	gold quality
palpebral conjunctiva	UBERON:0001812	91.29	gold quality
upper leg skin	UBERON:0004262	91.22	gold quality
cortex of kidney	UBERON:0001225	91.07	gold quality
pancreas	UBERON:0001264	91.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.02	gold quality
body of stomach	UBERON:0001161	90.97	gold quality
colonic mucosa	UBERON:0000317	90.74	gold quality
transverse colon	UBERON:0001157	90.72	gold quality
mucosa of transverse colon	UBERON:0004991	90.62	gold quality
esophagus mucosa	UBERON:0002469	90.61	gold quality
metanephros cortex	UBERON:0010533	90.59	gold quality
muscle organ	UBERON:0001630	90.54	gold quality
minor salivary gland	UBERON:0001830	90.47	gold quality
thoracic mammary gland	UBERON:0005200	90.43	gold quality
mammary gland	UBERON:0001911	90.39	gold quality
islet of Langerhans	UBERON:0000006	90.36	gold quality
saliva-secreting gland	UBERON:0001044	90.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.30	gold quality
renal medulla	UBERON:0000362	90.23	gold quality
stomach	UBERON:0000945	90.08	gold quality
tonsil	UBERON:0002372	90.07	gold quality
mouth mucosa	UBERON:0003729	90.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.96	gold quality
right uterine tube	UBERON:0001302	89.95	gold quality
descending thoracic aorta	UBERON:0002345	89.94	gold quality
metanephros	UBERON:0000081	89.87	gold quality
urinary bladder	UBERON:0001255	89.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.58	gold quality
skin of abdomen	UBERON:0001416	89.56	gold quality
duodenum	UBERON:0002114	89.53	gold quality
skin of leg	UBERON:0001511	89.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.36	gold quality
zone of skin	UBERON:0000014	89.15	gold quality
gingival epithelium	UBERON:0001949	89.12	silver quality
ventricular zone	UBERON:0003053	89.07	gold quality
gall bladder	UBERON:0002110	89.03	gold quality
gingiva	UBERON:0001828	88.99	gold quality
parotid gland	UBERON:0001831	88.97	gold quality
large intestine	UBERON:0000059	88.89	gold quality
esophagus	UBERON:0001043	88.89	gold quality
colon	UBERON:0001155	88.88	gold quality
intestine	UBERON:0000160	88.87	gold quality
thoracic aorta	UBERON:0001515	88.78	gold quality
renal glomerulus	UBERON:0000074	88.77	gold quality
small intestine	UBERON:0002108	88.72	gold quality
endometrium epithelium	UBERON:0004811	88.70	gold quality
deltoid	UBERON:0001476	88.63	gold quality
ascending aorta	UBERON:0001496	88.61	gold quality
lower esophagus mucosa	UBERON:0035834	88.54	gold quality
sperm	CL:0000019	88.44	silver quality
metanephric glomerulus	UBERON:0004736	88.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.20	gold quality
right ovary	UBERON:0002118	88.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	128.92
E-GEOD-99795	no	267.69
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	142.7
Corpus callosum	tissue	120.4
Hippocampal formation	tissue	117.1
Putamen	tissue	115.6
Prefrontal cortex	tissue	114.3
Cerebral cortex	tissue	114.3	not detected
Temporal cortex	tissue	114.1
Motor cortex	tissue	113.6
Thalamus	tissue	113.5
Amygdala	tissue	112.4
Substantia nigra	tissue	112.4
Ventral forebrain	tissue	112.4
Medulla oblongata	tissue	112.0
Midbrain	tissue	110.0
Liver	tissue	109.5	high
Entorhinal cortex	tissue	108.4
Somatosensory cortex	tissue	106.9
Insular cortex	tissue	106.6
Occipital cortex	tissue	104.8
Retrosplenial cortex	tissue	101.2
Basal ganglia	tissue	100.9	low
Periaqueductal gray	tissue	98.1
Septum	tissue	97.6
Retrosplenial and cingulate cortex	tissue	96.6
Superior colliculi	tissue	95.2
Pons	tissue	90.2
Hypothalamus	tissue	88.2
Olfactory bulb	tissue	68.9
Kidney	tissue	68.1	high
Cerebellum	tissue	58.6	not detected
Heart muscle	tissue	50.6	high
Breast	tissue	47.4	medium
Prostate	tissue	39.2	high
Thyroid gland	tissue	38.8	high
Tongue	tissue	34.1
Rectum	tissue	32.6	high
Adrenal gland	tissue	32.6	medium
Colon	tissue	27.9	high
Parathyroid gland	tissue	27.3	high
Epididymis	tissue	27.1	medium
Duodenum	tissue	26.3	high
Urinary bladder	tissue	24.6	high
Salivary gland	tissue	23.7	medium
Stomach 1	tissue	22.5	high
Pancreas	tissue	22.0	high
Skeletal muscle	tissue	21.8	not detected
Choroid plexus	tissue	20.1
Tonsil	tissue	19.4	medium
Caudate putamen	tissue	19.2
Adipose tissue	tissue	18.4	not detected
Cervix	tissue	18.3	medium
Small intestine	tissue	17.2	medium
Seminal vesicle	tissue	16.2	high
Esophagus	tissue	16.0	medium
Frontal cortex	tissue	14.7
Fallopian tube	tissue	14.2	medium
Lymph node	tissue	12.7	medium
Gallbladder	tissue	11.7	high
Thymus	tissue	11.6
Placenta	tissue	11.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (142.7), White matter (120.4), Subiculum (117.1), Dorsal spinal cord (116.0), Ventral hippocampus (107.2).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 1.87e-10, LOEUF 0.832, missense Z 0.459 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000340941 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 15)

• factors other than the genotype at the MCCA and MCCB loci have a major influence on the phenotype of MCC deficiency (PMID:16010683)
• The amino-termini containing 20 amino acids (MCCbeta) were both necessary and sufficient for targeting. Structural requirements for mitochondrial import were defined by site-directed mutagenesis. (PMID:16023992)
• The Kd value of soraphen A for the BC domains of human ACC1 and ACC2 is 1 nM. This high binding affinity is mainly due to the extensive interactions between soraphen A and the human biotin carboxylase domain (PMID:17876819)
• Molecular analyses revealed novel mutations in one of the causative genes, MCCA or MCCB, in all five of the MCC deficiency patients (PMID:17968484)
• identified two novel MCCA and four novel MCCB mutant alleles from five MCC-deficient patients (PMID:21071250)
• study reports eight different mutant alleles of MCCC1 or MCCC2 including six novel mutations in Korean patients with 3-methylcrotonyl-CoA carboxylase (MCC) deficiency (PMID:22150417)
• Mutation in 3-methylcrotonyl CoA carboxylase 2 gene is associated with 3-methylcrotonyl-CoA carboxylase deficiency. (PMID:22264772)
• Novel mutation in MCCC2 gene was identified in Chinese population. (PMID:25382614)
• This study reports data mainly obtained from the Portuguese newborn screening program collected over a ten-year period. Analysis of the MCCC1 and MCCC2 genes yielded 26 previously unreported mutations and a variant of clinically unknown significance. (PMID:27601257)
• MCCC2 overexpression predicts an unfavorable prognosis and promotes cell proliferation in breast cancer (PMID:30895811)
• Mutations on MCCC1 and MCCC2 genes are the major genetic causes for the increased C5-OH in neonates (PMID:31901042)
• MCCC2 overexpression predicts poorer prognosis and promotes cell proliferation in colorectal cancer. (PMID:32205097)
• [Analysis of MCCC2 gene variant in a pedigree affected with 3-methylcrotonyl coenzyme A carboxylase deficiency]. (PMID:33423264)
• MCCC2 is a novel mediator between mitochondria and telomere and functions as an oncogene in colorectal cancer. (PMID:37828426)
• ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis. (PMID:38783226)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mccc2	ENSDARG00000017571
mus_musculus	Mccc2	ENSMUSG00000021646
rattus_norvegicus	Mccc2	ENSRNOG00000017752
drosophila_melanogaster	Mccc2	FBGN0042083
caenorhabditis_elegans		WBGENE00303021

Paralogs (1): PCCB (ENSG00000114054)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1925288) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
decreased mean corpuscular volume	1
increased erythrocyte cell number	1
decreased mean corpuscular hemoglobin	1
increased prepulse inhibition	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mycobacterium tuberculosis CDC1551	P9WQH6	99.8%	Diamond
Mycobacterium tuberculosis H37Rv	P9WQH7	99.8%	Diamond
Bos taurus	Q2TBR0	96.1%	Diamond
Sus scrofa	P79384	95.2%	Diamond
Mycobacterium leprae TN	P53002	88.7%	Diamond
Roseobacter denitrificans OCh 114	Q168G2	83.5%	Diamond
Cereibacter sphaeroides 2.4.1	Q3J4E3	83.5%	Diamond
Rhodococcus erythropolis	Q06101	71.7%	Diamond
Saccharopolyspora erythraea NRRL 2338	P53003	70.6%	Diamond
Dictyostelium discoideum	Q8T2J9	69.2%	Diamond
Propionigenium modestum	O54028	66.6%	Diamond
Veillonella parvula	Q57079	66.6%	Diamond
Arabidopsis thaliana	Q9LDD8	62.0%	Diamond
Haloferax mediterranei ATCC 33500	I3R7F1	61.1%	Diamond
Propionibacterium freudenreichii subsp. shermanii	Q8GBW6	59.2%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P54541	56.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CARTPT	protein-coding	9607
LINC02197	ncRNA	102724392
BDP1	protein-coding	55814

Protein

Protein identifiers

Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial — Q9HCC0 (reviewed: Q9HCC0)

Alternative names: 3-methylcrotonyl-CoA carboxylase 2, 3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit, 3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta

All UniProt accessions (23): A0A0D9SFE9, A0A0S2Z5R4, A0A140VK29, A0A804HHS4, A0A804HIH3, A0A804HIQ3, A0A804HJ24, A0A804HJ31, A0A804HJ84, A0A804HJC1, A0A804HJL2, A0A804HJW2, A0A804HJW5, A0A804HK37, A0A804HKE8, A0A804HKH3, A0A804HKN6, A0A804HL02, A0A804HLJ9, D6R9R1, D6RD67, D6RDF7, Q9HCC0

UniProt curated annotations — full annotation on UniProt →

Function. Carboxyltransferase 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.

Subunit / interactions. Probably a dodecamer composed of six biotin-containing alpha subunits (MCCC1) and six beta (MCCC2) subunits.

Subcellular location. Mitochondrion matrix.

Disease relevance. 3-methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D) [MIM:210210] 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. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 2/3.

Similarity. Belongs to the AccD/PCCB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HCC0-1	1	yes
Q9HCC0-2	2

RefSeq proteins (2): NP_001350076, NP_071415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011762	COA_CT_N	Domain
IPR011763	COA_CT_C	Domain
IPR029045	ClpP/crotonase-like_dom_sf	Homologous_superfamily
IPR034733	AcCoA_carboxyl_beta	Domain
IPR045190	MCCB/AccD1-like	Family

Pfam: PF01039

Enzyme classification (BRENDA)

• EC 6.4.1.4 — methylcrotonoyl-CoA carboxylase (BRENDA: 25 organisms, 44 substrates, 33 inhibitors, 45 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-METHYLCROTONOYL-COA	0.0098–31	19
ATP	0.01–21	11
HCO3-	0.0008–2.2	7
(E)-CROTONOYL-COA	0.138–0.225	2
(2Z)-3-ETHYLCROTONOYL-COA	0.022	1
3-METHYLCROTONYL-COA	0.074	1
BICARBONATE	2.8	1
CROTONOYL-COA	0.11	1

Catalyzed reactions (Rhea)

• 3-methylbut-2-enoyl-CoA + hydrogencarbonate + ATP = 3-methyl-(2E)-glutaconyl-CoA + ADP + phosphate + H(+) (RHEA:13589)

UniProt features (135 total): sequence variant 61, helix 31, strand 22, turn 8, modified residue 6, domain 2, region of interest 2, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

14 structures by resolution:

PDB	Title	Method	Resolution (Å)
8XL6	Structure of human 3-methylcrotonyl-CoA carboxylase at apo-state (MCC-Apo)	ELECTRON MICROSCOPY	2.29
8XL8	Structure of human 3-methylcrotonyl-CoA carboxylase in complex with propionyl-CoA …	ELECTRON MICROSCOPY	2.36
8JAW	Human MCC in MCCD state	ELECTRON MICROSCOPY	2.51
8JAK	Human MCC in MCCU state	ELECTRON MICROSCOPY	2.52
8J7D	Human 3-methylcrotonyl-CoA carboxylase in BCCP-H1 state	ELECTRON MICROSCOPY	2.7
8J4Z	Human 3-methylcrotonyl-CoA carboxylase in BCCP-CTS state with substrate	ELECTRON MICROSCOPY	2.73
8XL7	Structure of human 3-methylcrotonyl-CoA carboxylase in complex with acetyl-CoA (MCC-ACO)	ELECTRON MICROSCOPY	2.85
8J99	Human 3-methylcrotonyl-CoA carboxylase in BCS-mcoa state	ELECTRON MICROSCOPY	2.87
8JXL	Human 3-methylcrotonyl-CoA carboxylase in MCCU state with MCoA	ELECTRON MICROSCOPY	2.98
8JXN	Human 3-methylcrotonyl-CoA carboxylase in BCCP-H1 state with MCoA	ELECTRON MICROSCOPY	3.2
8JXM	Human 3-methylcrotonyl-CoA carboxylase in BCCP-H2 state with MCoA	ELECTRON MICROSCOPY	3.49
8K2V	3-Methylcrotonyl-CoA Carboxylase in MCCD state with Acetyl CoA	ELECTRON MICROSCOPY	3.52
8J78	Human 3-methylcrotonyl-CoA carboxylase in BCCP-H2 state	ELECTRON MICROSCOPY	3.88
8J73	Methylcrotonoyl-CoA carboxylase core-Dimer	ELECTRON MICROSCOPY	4.16

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCC0-F1	94.82	0.93

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH enhanced · IF enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6)

Type	Positions
N6-succinyllysine	495, 70, 141
N6-acetyllysine	511, 70, 495

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 13; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-9909438	3-Methylcrotonyl-CoA carboxylase deficiency ⚕	—
R-HSA-3371599	Defective HLCS causes multiple carboxylase deficiency ⚕	—
R-HSA-3323169	Defects in biotin (Btn) metabolism ⚕	—
R-HSA-3296482	Defects in vitamin and cofactor metabolism ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9865118	Diseases of branched-chain amino acid catabolism ⚕	—
R-HSA-5668914	Diseases of metabolism ⚕	—
R-HSA-196780	Biotin transport and metabolism	—
R-HSA-70895	Branched-chain amino acid catabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	—

MSigDB gene sets: 276 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_COENZYME_A_METABOLIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, PRAMOONJAGO_SOX4_TARGETS_DN, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, SMID_BREAST_CANCER_LUMINAL_B_UP, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (3): L-leucine catabolic process (GO:0006552), branched-chain amino acid catabolic process (GO:0009083), coenzyme A metabolic process (GO:0015936)

GO Molecular Function (5): methylcrotonoyl-CoA carboxylase activity (GO:0004485), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), methylcrotonoyl-CoA carboxylase complex (GO:1905202)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Metabolism	2
Diseases of metabolism	2
Metabolism of water-soluble vitamins and cofactors	1
Defects in biotin (Btn) metabolism	1
Metabolism of amino acids and derivatives	1
Diseases of branched-chain amino acid catabolism	1
Metabolism of vitamins and cofactors	1
Defects in vitamin and cofactor metabolism	1
Disease	1

GO top-level categories

23 GO namespaces:

Category	Terms
cytoplasm	2
L-leucine metabolic process	1
branched-chain amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
amino acid catabolic process	1
branched-chain amino acid metabolic process	1
carboxylic acid catabolic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
CoA carboxylase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
L-leucine catabolic process	BP	mutant phenotype
methylcrotonoyl-CoA carboxylase complex	CC	direct assay
mitochondrial matrix	CC	direct assay
mitochondrion	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,554 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCCC2	MCCC1	Q96RQ3	980
MCCC2	USHBP1	Q8N6Y0	957
MCCC2	MCC	P23508	908
MCCC2	BTD	P43251	780
MCCC2	PCCA	P05165	776
MCCC2	BCKDHB	P21953	620
MCCC2	IVD	P26440	576
MCCC2	HLCS	P50747	532
MCCC2	BCKDHA	P12694	518
MCCC2	ACADSB	P45954	505
MCCC2	HMGCL	P35914	491
MCCC2	ECI2	O75521	480
MCCC2	SUCLG2	Q96I99	472
MCCC2	HSDL2	Q6YN16	471
MCCC2	HIBADH	P31937	461

IntAct

Human interaction partners of MCCC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
MCCC1	physical association	0.820	4
CFTR	physical association	0.520	1
HSPB2	physical association	0.370	1
ALDH1L1	association	0.350	2
CYB5B	association	0.350	2

BioGRID (192 interactions; top human partners by supporting records): ECH1 (Affinity Capture-MS; 4 records), MCCC1 (Co-fractionation; 4 records), PCCA (Affinity Capture-MS; 4 records), PARK2 (Affinity Capture-MS; 3 records), AGR2 (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-MS; 2 records), CFTR (PCA; 2 records), CUL3 (Affinity Capture-MS; 2 records), MYC (Affinity Capture-MS; 2 records), PRNP (Affinity Capture-MS; 2 records), RECK (Affinity Capture-MS; 2 records), TP53 (Affinity Capture-MS; 2 records), ACACA (Affinity Capture-MS), ADRB2 (Affinity Capture-MS), ARL5A (Proximity Label-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
MCCC2	“form complex”	“Methylcrotonyl-CoA carboxylase complex”	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
3-Methylcrotonyl-CoA carboxylase	2	MCCC1, MCCC2

Disease & clinical

Genetic variants

Variant evidence for MCCC2: 943 ClinVar records (161 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

943 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	69
Likely pathogenic	92
Uncertain significance	286
Likely benign	309
Benign	61

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 161 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1919	NM_022132.5(MCCC2):c.517dup (p.Ser173fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1928	NM_022132.5(MCCC2):c.1574+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	4
286933	NM_022132.5(MCCC2):c.214C>T (p.Arg72Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1924	NM_022132.5(MCCC2):c.803G>C (p.Arg268Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
582906	NM_022132.5(MCCC2):c.735dup (p.Val247fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
963404	NM_022132.5(MCCC2):c.181G>T (p.Glu61Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1098284	NM_022132.5(MCCC2):c.592C>T (p.Gln198Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
449392	NM_022132.5(MCCC2):c.449_450del (p.Val150fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
938097	NM_022132.5(MCCC2):c.512-1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1402549	NM_022132.5(MCCC2):c.1144_1147inv (p.Lys382_Lys383delinsPheTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
575151	NM_022132.5(MCCC2):c.653C>T (p.Ala218Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
1036699	NM_022132.5(MCCC2):c.1300G>C (p.Val434Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
535829	NM_022132.5(MCCC2):c.1216+2T>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
950084	NM_022132.5(MCCC2):c.578G>A (p.Arg193His)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
1474479	NM_022132.5(MCCC2):c.383+2del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4

Per-variant reference — Sugi Variant

Explore MCCC2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 1,986):

Position(s)	Effect	Δscore	Sites
5:71592924–71592925	acceptor_loss	1.0000	6
5:71592989	donor_gain	1.0000
5:71592993–71592994	donor_loss	1.0000	5
5:71599657–71599658	acceptor_loss	1.0000	4
5:71599761–71599762	donor_loss	1.0000	3
5:71632119–71632120	acceptor_loss	1.0000	5
5:71632186–71632187	donor_loss	1.0000	5
5:71634920	acceptor_gain	1.0000
5:71635146	acceptor_gain	1.0000
5:71635149–71635150	acceptor_loss	1.0000	6

AlphaMissense

1,468 missense substitutions predicted likely pathogenic (of 3,655 scored), across 391 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M473	9	0.893	0.970
M452	9	0.864	0.972
F387	8	0.972	0.995
D340	8	0.966	0.990
D529	8	0.954	0.985
F185	8	0.941	0.994
F407	8	0.941	0.999
F400	8	0.937	0.993
F195	8	0.911	0.991
D274	8	0.910	0.961
H266	8	0.907	0.979
D528	8	0.896	0.970
D92	8	0.870	0.920
N403	8	0.870	0.986
D172	8	0.854	0.960
D228	8	0.846	0.943
D137	8	0.845	0.942
F240	7	0.965	0.995
F347	7	0.962	0.992
E414	7	0.948	0.993

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.19e-07
Kidney Chromophobe (TCGA)	unfavorable	0.000331

Disease associations

OMIM: gene MIM:609014 | disease phenotypes: MIM:210210, MIM:210200, MIM:271150

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
3-methylcrotonyl-CoA carboxylase 2 deficiency	Definitive	Autosomal recessive	5
3-methylcrotonyl-CoA carboxylase deficiency	Definitive	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
3-methylcrotonyl-CoA carboxylase deficiency	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (4): 3-methylcrotonyl-CoA carboxylase 2 deficiency (MONDO:0008862), 3-methylcrotonyl-CoA carboxylase deficiency (MONDO:0018950), autism spectrum disorder (MONDO:0005258), spinal muscular atrophy, type IV (MONDO:0010056)

Orphanet (3): 3-methylcrotonyl-CoA carboxylase deficiency (Orphanet:6), Proximal spinal muscular atrophy type 4 (Orphanet:83420), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

36 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001051	Seborrheic dermatitis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001531	Failure to thrive in infancy
HP:0001596	Alopecia
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001987	Hyperammonemia
HP:0001992	Organic aciduria
HP:0001993	Ketoacidosis
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002179	Opisthotonus
HP:0002919	Ketonuria
HP:0003108	Hyperglycinuria
HP:0003202	Skeletal muscle atrophy
HP:0003234	Decreased circulating carnitine concentration
HP:0003353	Propionyl-CoA carboxylase deficiency
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0004357	Abnormal circulating leucine concentration
HP:0008281	Acute hyperammonemia
HP:0010911	Hyperleucinemia
HP:0011968	Feeding difficulties
HP:0100021	Cerebral palsy
HP:0100022	Abnormality of movement
HP:0100659	Abnormal cerebral vascular morphology

GWAS associations

2 associations:

Study	Trait	p-value
GCST008953_3	Chromosomal aberration frequency (chromatid type)	6e-6
GCST009391_809	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0009862	chromatid-type aberration frequency
EFO:0010394	sphingomyelin 18:1 measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C535309	3-methylcrotonyl CoA carboxylase 2 deficiency *(supp.)*
C563948	Spinal Muscular Atrophy, Type IV *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067224 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.99	Kd	101.9	nM	CHEMBL5653589
6.99	ED50	101.9	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148729: Binding affinity to human MCCC2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1019	uM

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
bisphenol F	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
methylselenic acid	decreases expression	1
beta-lapachone	decreases expression	1
methylparaben	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Irinotecan	decreases expression, affects cotreatment, affects response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, decreases expression	1
Demecolcine	increases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651771	Binding	Binding affinity to human MCCC2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
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NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
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NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
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NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MCCC2 across ~30M SureChEMBL compounds — explore on Sugi Predict.