MLYCD

Summary

MLYCD (malonyl-CoA decarboxylase, HGNC:7150) is a protein-coding gene on chromosome 16q23.3, encoding Malonyl-CoA decarboxylase, mitochondrial (O95822). Catalyzes the conversion of malonyl-CoA to acetyl-CoA.

The product of this gene catalyzes the breakdown of malonyl-CoA to acetyl-CoA and carbon dioxide. Malonyl-CoA is an intermediate in fatty acid biosynthesis, and also inhibits the transport of fatty acyl CoAs into mitochondria. Consequently, the encoded protein acts to increase the rate of fatty acid oxidation. It is found in mitochondria, peroxisomes, and the cytoplasm. Mutations in this gene result in malonyl-CoA decarboyxlase deficiency.

Source: NCBI Gene 23417 — RefSeq curated summary.

At a glance

• Gene–disease (curated): malonic aciduria (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 615 total — 45 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_012213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7150
Approved symbol	MLYCD
Name	malonyl-CoA decarboxylase
Location	16q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MCD, hMCD
Ensembl gene	ENSG00000103150
Ensembl biotype	protein_coding
OMIM	606761
Entrez	23417

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000262430, ENST00000561562, ENST00000563312, ENST00000566309, ENST00000569024, ENST00000851350, ENST00000851351

RefSeq mRNA: 1 — MANE Select: NM_012213 NM_012213

CCDS: CCDS42206

Canonical transcript exons

ENST00000262430 — 5 exons

Exon	Start	End
ENSE00000695181	83906987	83907099
ENSE00000695183	83908126	83908282
ENSE00001103932	83914956	83927031
ENSE00001184412	83899115	83899672
ENSE00003891200	83912218	83912367

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 94.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5014 / max 162.6680, expressed in 1788 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155269	10.0087	1785
155270	0.4927	214

Top tissues by expression

271 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.85	gold quality
diaphragm	UBERON:0001103	94.47	gold quality
heart left ventricle	UBERON:0002084	93.87	gold quality
cardiac ventricle	UBERON:0002082	93.58	gold quality
apex of heart	UBERON:0002098	93.31	gold quality
heart right ventricle	UBERON:0002080	91.76	gold quality
right atrium auricular region	UBERON:0006631	90.67	gold quality
gastrocnemius	UBERON:0001388	90.41	gold quality
heart	UBERON:0000948	90.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.24	gold quality
cardiac atrium	UBERON:0002081	89.92	gold quality
muscle of leg	UBERON:0001383	89.51	gold quality
biceps brachii	UBERON:0001507	89.05	gold quality
vastus lateralis	UBERON:0001379	89.04	silver quality
muscle organ	UBERON:0001630	89.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.34	gold quality
quadriceps femoris	UBERON:0001377	87.91	silver quality
skeletal muscle tissue	UBERON:0001134	87.28	gold quality
triceps brachii	UBERON:0001509	86.93	gold quality
myocardium	UBERON:0002349	86.66	silver quality
muscle tissue	UBERON:0002385	86.21	gold quality
right lobe of liver	UBERON:0001114	85.99	gold quality
sural nerve	UBERON:0015488	85.93	gold quality
gluteal muscle	UBERON:0002000	85.68	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.44	silver quality
oocyte	CL:0000023	85.04	gold quality
left ventricle myocardium	UBERON:0006566	84.56	silver quality
liver	UBERON:0002107	84.55	gold quality
parotid gland	UBERON:0001831	83.94	gold quality
secondary oocyte	CL:0000655	83.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PPARGC1A

miRNA regulators (miRDB)

36 targeting MLYCD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-146B-3P	97.83	65.29	782

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• Malonyl-CoA decarboxylase deficiency may result from MLYCD mutations that result in protein mistargeting. (PMID:12955715)
• The concentration of malonyl-CoA is diminished in muscle after physical training, most likely because of PGC-1alpha-mediated increases in MCD expression and activity. (PMID:16434556)
• analysis of nine novel MLYCD mutations in patients with malonyl-coenzyme A decarboxylase deficiency (PMID:17186413)
• MCD silencing suppresses lipid uptake and enhances glucose uptake in primary human myotubes. (PMID:18314420)
• Data suggest that increased expression of malonyl CoA decarboxylase, and the decreased expression of acetyl CoA carboxylase and 5’-AMP activated protein kinase are important regulators of the maturation of fatty acid oxidation in the newborn human heart. (PMID:18614968)
• This study of fatty acid oxidation and malonyl-CoA decarboxylase identifies a critical role for metabolism in both the normal pulmonary circulation (hypoxic pulmonary vasoconstriction) and pulmonary hypertension (PMID:20702857)
• Our case emphasizes the need for ongoing cardiac disease screening in patients with MCD deficiency and the benefits and limitations of current dietary interventions. (PMID:22778304)
• Structural asymmetry and disulfide bridges among subunits modulate the activity of human malonyl-CoA decarboxylase. (PMID:23482565)
• The MLYCD catalytic domain is structurally homologous to those of the GCN5-related N-acetyltransferase superfamily. (PMID:23791943)
• Our result expands the phenotype of malonyl-CoA decarboxylase deficiency and suggests attentions should be paid to the mild form of disorders, for example, malonyl-CoA decarboxylase deficiency, which usually present a severe disease course. (PMID:26858006)
• To identify the active site of MCD, molecular docking and molecular dynamics simulations were performed to explore the interactions of human mitochondrial MCD (HmMCD) and CoA derivatives. The findings reveal that the active site of HmMCD indeed resides in the prominent groove which resembles that of curacin A. (PMID:26948533)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mlycd	ENSDARG00000104732
mus_musculus	Mlycd	ENSMUSG00000074064
rattus_norvegicus	Mlycd	ENSRNOG00000014522
caenorhabditis_elegans		WBGENE00009439

Protein

Protein identifiers

Malonyl-CoA decarboxylase, mitochondrial — O95822 (reviewed: O95822)

All UniProt accessions (4): O95822, A0A087X1B8, V9GY18, V9GYW3

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homotetramer. Dimer of dimers. The two subunits within a dimer display conformational differences suggesting that at any given moment, only one of the two subunits is competent for malonyl-CoA binding and catalytic activity. Under oxidizing conditions, can form disulfide-linked homotetramers (in vitro). Associates with the peroxisomal targeting signal receptor PEX5.

Subcellular location. Cytoplasm. Mitochondrion matrix. Peroxisome. Peroxisome matrix.

Tissue specificity. Expressed in fibroblasts and hepatoblastoma cells (at protein level). Expressed strongly in heart, liver, skeletal muscle, kidney and pancreas. Expressed in myotubes. Expressed weakly in brain, placenta, spleen, thymus, testis, ovary and small intestine.

Post-translational modifications. Acetylation at Lys-472 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-472 by SIRT4 represses activity, leading to promote lipogenesis. Interchain disulfide bonds may form in peroxisomes (Potential). Interchain disulfide bonds are not expected to form in the reducing environment of the cytoplasm and mitochondria.

Disease relevance. Malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360] Autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions. Formation of interchain disulfide bonds leads to positive cooperativity between active sites and increases the affinity for malonyl-CoA and the catalytic efficiency (in vitro).

Pathway. Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis; acetyl-CoA from malonyl-CoA: step 1/1.

Miscellaneous. May be produced by alternative initiation at Met-40 of isoform mitochondrial. Alternatively, represents a proteolytic processed form of the mitochondrial form.

Isoforms (2)

UniProt ID	Names	Canonical?
O95822-1	Mitochondrial	yes
O95822-2	Cytoplasmic+peroxisomal

RefSeq proteins (1): NP_036345* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007956	Malonyl_CoA_deC_C	Domain
IPR035372	MCD_N	Domain
IPR038351	MCD_N_sf	Homologous_superfamily
IPR038917	Malonyl_CoA_deC	Family
IPR042303	Malonyl_CoA_deC_C_sf	Homologous_superfamily

Pfam: PF05292, PF17408

Enzyme classification (BRENDA):

• EC 4.1.1.9 — malonyl-CoA decarboxylase (BRENDA: 22 organisms, 67 substrates, 476 inhibitors, 38 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MALONYL-COA	0.0087–1.16	33
N-HYDROXY-L-ORNITHINE	0.025	1

Catalyzed reactions (Rhea), 1 shown:

• malonyl-CoA + H(+) = acetyl-CoA + CO2 (RHEA:18781)

UniProt features (70 total): helix 26, strand 10, modified residue 7, mutagenesis site 7, sequence conflict 4, turn 3, binding site 3, region of interest 2, active site 2, transit peptide 1, chain 1, site 1, disulfide bond 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2YGW	X-RAY DIFFRACTION	2.8
4F0X	X-RAY DIFFRACTION	3.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95822-F1	90.16	0.80

Functional residue map

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

Catalytic / active sites (3): 211 (essential for catalytic activity); 329 (proton acceptor); 423 (proton donor)

Ligand- & substrate-binding residues (3): 299–305; 329; 423

Post-translational modifications (7): 59, 168, 168, 211, 222, 389, 472

Disulfide bonds (1): 206

Mutagenesis-validated functional residues (7):

Position	Phenotype
206	abolishes formation of disulfide-linked homotetramers. abolishes the cooperative enzyme kinetics that are seen under oxi
243	does not abolish formation of disulfide-linked homotetramers. no effect on development of cooperative enzyme kinetics in
290	2-fold reduction in catalytic activity.
302	decreases catalytic activity. increases affinity for malonyl-coa.
329	110-fold reduction in catalytic activity.
423	7-fold reduction in catalytic activity.
456	3.5-fold reduction in catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390247	Beta-oxidation of very long chain fatty acids
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 251 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, MODULE_255, GCANCTGNY_MYOD_Q6, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (13): response to ischemia (GO:0002931), acetyl-CoA biosynthetic process (GO:0006085), fatty acid biosynthetic process (GO:0006633), acyl-CoA metabolic process (GO:0006637), response to nutrient (GO:0007584), regulation of glucose metabolic process (GO:0010906), fatty acid oxidation (GO:0019395), regulation of fatty acid beta-oxidation (GO:0031998), positive regulation of fatty acid oxidation (GO:0046321), malonyl-CoA catabolic process (GO:2001294), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), regulation of fatty acid oxidation (GO:0046320)

GO Molecular Function (4): identical protein binding (GO:0042802), malonyl-CoA decarboxylase activity (GO:0050080), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831)

GO Cellular Component (6): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peroxisomal lipid metabolism	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid metabolic process	2
regulation of fatty acid oxidation	2
fatty acid oxidation	2
cellular anatomical structure	2
cytoplasm	2
response to stress	1
acetyl-CoA metabolic process	1
acyl-CoA biosynthetic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
response to nutrient levels	1
response to chemical	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
lipid oxidation	1
fatty acid beta-oxidation	1
regulation of lipid catabolic process	1
positive regulation of fatty acid metabolic process	1
sulfur compound catabolic process	1
purine-containing compound catabolic process	1
nucleoside phosphate catabolic process	1
malonyl-CoA metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
regulation of fatty acid metabolic process	1
protein binding	1
carboxy-lyase activity	1
catalytic activity	1
carbon-carbon lyase activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
microbody	1
peroxisome	1

Protein interactions and networks

STRING

1227 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MLYCD	ACACA	Q13085	675
MLYCD	SREBF1	P36956	630
MLYCD	SIRT4	Q9Y6E7	597
MLYCD	CPT2	P23786	593
MLYCD	PPARA	Q07869	586
MLYCD	ACADM	P11310	578
MLYCD	CPT1A	P50416	562
MLYCD	ACADL	P28330	546
MLYCD	ACADVL	P49748	541
MLYCD	CPT1C	Q8TCG5	538
MLYCD	ACACB	O00763	535
MLYCD	ACSF3	Q4G176	526
MLYCD	PPARGC1A	Q9UBK2	522
MLYCD	SIRT5	Q9NXA8	520
MLYCD	FASN	P49327	519

IntAct

50 interactions, top by confidence:

A	B	Type	Score
MLYCD	MLYCD	psi-mi:“MI:0407”(direct interaction)	0.640
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
TMEM88	MLYCD	psi-mi:“MI:0914”(association)	0.530
FGF11	CHD1	psi-mi:“MI:0914”(association)	0.530
IL25	PPM1B	psi-mi:“MI:0914”(association)	0.530
TPST1	TPST2	psi-mi:“MI:0914”(association)	0.530
MLYCD	NUMA1	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ADCK1	MLYCD	psi-mi:“MI:0914”(association)	0.350
COQ6	TIMM44	psi-mi:“MI:0914”(association)	0.350
COQ6	NRDC	psi-mi:“MI:0914”(association)	0.350
ADCK1	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
CHCHD2	ACSL4	psi-mi:“MI:0914”(association)	0.350
TAMM41	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
TRUB2	NME6	psi-mi:“MI:0914”(association)	0.350
CHCHD2	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
COQ6	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
CAMKK2	FEZF1	psi-mi:“MI:0914”(association)	0.350
CEP135	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CEP135	WWP2	psi-mi:“MI:0914”(association)	0.350
CEP135	WDR91	psi-mi:“MI:0914”(association)	0.350
FGF11	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
IL25	MANBA	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	AREL1	psi-mi:“MI:0914”(association)	0.350
CFAP107	KDM6A	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS), MLYCD (Two-hybrid), UBALD1 (Two-hybrid), NUMA1 (Proximity Label-MS), MLYCD (Affinity Capture-MS), MLYCD (Affinity Capture-MS)

ESM2 similar proteins: A0A068ACU9, A0A0S6XGG4, A0A0S6XGG5, A0A0U5GNT1, A0A1B4XBH6, A0A1B4XBK1, A0A1B5L8S2, A0A1C8AX29, A0A1L9WUM2, A0A1W5T1Y7, A0A346RP51, A0A411KUP9, A0A481WQ01, A0A4P8W7Y2, A0A6J4B4M6, A0A7L8UVC6, A0A7L9F0X4, A0A8F4NU75, A0A8F4NUL3, A1CLZ0, A8AKP9, B7LNG1, G4MVZ4, H1AE12, O02734, O95822, P12617, P34913, P34914, P80299, P9WEU7, P9WEZ7, Q00706, Q0JJD4, Q0V6Q1, Q2KIE6, Q4WAZ8, Q4WD45, Q4WZB3, Q5AV07

Diamond homologs: O95822, P12617, Q920F5, Q99J39

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	9
Uncertain significance	217
Likely benign	276
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070667	NM_012213.3(MLYCD):c.642-2A>C	Pathogenic
1323278	NM_012213.3(MLYCD):c.368dup (p.Gln124fs)	Pathogenic
1323279	NM_012213.3(MLYCD):c.758del (p.Leu253fs)	Pathogenic
1400055	NM_012213.3(MLYCD):c.22_34dup (p.Arg12fs)	Pathogenic
1458761	NC_000016.9:g.(?83932750)(84056514_?)del	Pathogenic
1806239	NM_012213.3(MLYCD):c.175A>T (p.Lys59Ter)	Pathogenic
2013700	NM_012213.3(MLYCD):c.583del (p.Phe194_Leu195insTer)	Pathogenic
203813	NM_012213.3(MLYCD):c.475del (p.Ala159fs)	Pathogenic
2137849	NM_012213.3(MLYCD):c.393_400del (p.Leu133fs)	Pathogenic
2137851	NM_012213.3(MLYCD):c.953_954del	Pathogenic
2174042	NM_012213.3(MLYCD):c.674del (p.Met225fs)	Pathogenic
2695851	NM_012213.3(MLYCD):c.640G>T (p.Glu214Ter)	Pathogenic
2705148	NM_012213.3(MLYCD):c.2T>C (p.Met1Thr)	Pathogenic
2713597	NM_012213.3(MLYCD):c.199C>T (p.Gln67Ter)	Pathogenic
2762272	NM_012213.3(MLYCD):c.248_252del (p.Gln83fs)	Pathogenic
2762813	NM_012213.3(MLYCD):c.225C>G (p.Tyr75Ter)	Pathogenic
2827180	NM_012213.3(MLYCD):c.682A>T (p.Lys228Ter)	Pathogenic
2846533	NC_000016.10:g.83914954AG[2]	Pathogenic
2846964	NM_012213.3(MLYCD):c.343C>T (p.Gln115Ter)	Pathogenic
2847635	NM_012213.3(MLYCD):c.537_538del (p.Asn179fs)	Pathogenic
2849603	NM_012213.3(MLYCD):c.796dup (p.Gln266fs)	Pathogenic
2854885	NM_012213.3(MLYCD):c.376G>T (p.Glu126Ter)	Pathogenic
2882163	NM_012213.3(MLYCD):c.721del (p.Ser241fs)	Pathogenic
2888559	NM_012213.3(MLYCD):c.124G>T (p.Glu42Ter)	Pathogenic
2890013	NM_012213.3(MLYCD):c.22_34del (p.Leu8fs)	Pathogenic
2955855	NM_012213.3(MLYCD):c.346C>T (p.Gln116Ter)	Pathogenic
2986225	NM_012213.3(MLYCD):c.743_753dup (p.Val252fs)	Pathogenic
2987390	NM_012213.3(MLYCD):c.193G>T (p.Glu65Ter)	Pathogenic
3243344	NC_000016.9:g.(?83948541)(83949094_?)del	Pathogenic
3243345	NC_000016.9:g.(?83932750)(83941907_?)del	Pathogenic

SpliceAI

1822 predictions. Top by Δscore:

Variant	Effect	Δscore
16:83907096:G:GG	donor_gain	1.0000
16:83907097:TGA:T	donor_gain	1.0000
16:83907098:GA:G	donor_gain	1.0000
16:83907098:GAG:G	donor_gain	1.0000
16:83907100:G:GG	donor_gain	1.0000
16:83908111:T:G	acceptor_gain	1.0000
16:83908112:A:AG	acceptor_gain	1.0000
16:83908113:A:G	acceptor_gain	1.0000
16:83908278:TCCAG:T	donor_loss	1.0000
16:83908279:CCAG:C	donor_loss	1.0000
16:83908280:CAGG:C	donor_loss	1.0000
16:83912363:TGCAG:T	donor_loss	1.0000
16:83912365:CAGG:C	donor_loss	1.0000
16:83912365:CAGGT:C	donor_loss	1.0000
16:83912366:AGGTA:A	donor_loss	1.0000
16:83912367:GGTAA:G	donor_loss	1.0000
16:83912368:GTAAG:G	donor_loss	1.0000
16:83912369:T:G	donor_loss	1.0000
16:83899669:CCGG:C	donor_loss	0.9900
16:83899670:CGGGT:C	donor_loss	0.9900
16:83899671:GG:G	donor_gain	0.9900
16:83899672:GG:G	donor_gain	0.9900
16:83899673:G:GG	donor_gain	0.9900
16:83899674:T:C	donor_loss	0.9900
16:83906982:TTCA:T	acceptor_loss	0.9900
16:83906983:TCAGG:T	acceptor_loss	0.9900
16:83906984:CAG:C	acceptor_loss	0.9900
16:83906985:A:AG	acceptor_gain	0.9900
16:83906985:A:C	acceptor_loss	0.9900
16:83906985:AG:A	acceptor_gain	0.9900

AlphaMissense

3166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:83914986:A:C	S327R	0.998
16:83914988:T:A	S327R	0.998
16:83914988:T:G	S327R	0.998
16:83915278:T:C	L424P	0.998
16:83915302:G:C	R432P	0.998
16:83915287:G:A	G427E	0.997
16:83915016:T:A	W337R	0.996
16:83915016:T:C	W337R	0.996
16:83915020:T:C	L338P	0.996
16:83915220:T:G	Y405D	0.996
16:83915224:T:C	L406P	0.996
16:83915258:C:A	N417K	0.996
16:83915258:C:G	N417K	0.996
16:83915271:T:C	F422L	0.996
16:83915273:C:A	F422L	0.996
16:83915273:C:G	F422L	0.996
16:83915274:C:G	H423D	0.996
16:83915286:G:T	G427W	0.996
16:83915287:G:T	G427V	0.996
16:83915289:G:C	A428P	0.996
16:83915366:C:A	N453K	0.996
16:83915366:C:G	N453K	0.996
16:83899614:T:C	L157P	0.995
16:83907062:T:A	W202R	0.995
16:83907062:T:C	W202R	0.995
16:83912287:T:C	S290P	0.995
16:83914999:T:A	I331K	0.995
16:83915008:T:C	F334S	0.995
16:83915215:C:A	A403D	0.995
16:83915290:C:A	A428E	0.995

dbSNP variants (sampled 300 via entrez): RS1000167635 (16:83900823 A>G), RS1000193978 (16:83922114 T>C), RS1000249069 (16:83926001 C>T), RS1000255153 (16:83924399 G>T), RS1000293437 (16:83904629 A>G,T), RS1000443001 (16:83920515 C>G,T), RS1000682348 (16:83914815 A>AATCTT), RS1000704984 (16:83900852 G>A,C), RS1000733378 (16:83911114 C>G,T), RS1000787950 (16:83918414 CAG>C), RS1000841724 (16:83918304 A>G), RS1000957865 (16:83914716 C>A), RS1000987139 (16:83924863 T>A), RS1001029380 (16:83898073 G>C), RS1001135072 (16:83903724 A>G)

Disease associations

OMIM: gene MIM:606761 | disease phenotypes: MIM:248360

GenCC curated gene-disease

Disease	Classification	Inheritance
malonic aciduria	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
malonic aciduria	Definitive	AR

Mondo (2): malonic aciduria (MONDO:0009556), intellectual disability (MONDO:0001071)

Orphanet (2): Malonic aciduria (Orphanet:943), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001302	Pachygyria
HP:0001332	Dystonia
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001638	Cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001946	Ketosis
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002188	Delayed CNS myelination
HP:0002643	Neonatal respiratory distress
HP:0003128	Lactic acidosis
HP:0004322	Short stature
HP:0011664	Left ventricular noncompaction cardiomyopathy
HP:0011968	Feeding difficulties
HP:0012120	Methylmalonic aciduria
HP:0012450	Chronic constipation

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002935_4	Lead levels	3.000000e-07
GCST003830_13	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	1.000000e-06
GCST012034_9	Sleep (1/2-day periodicity)	2.000000e-08
GCST90011898_48	Alanine aminotransferase levels	1.000000e-19
GCST90011900_144	Serum alkaline phosphatase levels	1.000000e-24

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C535702	Malonic aciduria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4698 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Decarboxylases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 10h [PMID: 20832306]	Inhibition	9.3	pIC50

ChEMBL bioactivities

370 potent at pChembl≥5 of 381 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	IC50	0.07	nM	CHEMBL205986
9.54	IC50	0.29	nM	CHEMBL380487
9.30	IC50	0.5	nM	CHEMBL1258253
9.22	IC50	0.6	nM	CHEMBL1258254
9.07	IC50	0.85	nM	CHEMBL205506
9.05	IC50	0.9	nM	CHEMBL1257549
9.05	IC50	0.9	nM	CHEMBL1258367
9.01	IC50	0.98	nM	CHEMBL204287
9.00	IC50	1	nM	CHEMBL202688
8.96	IC50	1.1	nM	CHEMBL1257909
8.94	IC50	1.14	nM	CHEMBL206852
8.89	IC50	1.3	nM	CHEMBL1258699
8.85	IC50	1.4	nM	CHEMBL1258139
8.84	IC50	1.45	nM	CHEMBL202689
8.80	IC50	1.6	nM	CHEMBL1258935
8.80	IC50	1.6	nM	CHEMBL1258140
8.77	IC50	1.7	nM	CHEMBL1257548
8.74	IC50	1.8	nM	CHEMBL1257669
8.70	IC50	1.99	nM	CHEMBL202746
8.66	IC50	2.2	nM	CHEMBL1258820
8.64	IC50	2.3	nM	CHEMBL1258936
8.58	IC50	2.65	nM	CHEMBL203835
8.57	IC50	2.7	nM	CHEMBL1258591
8.51	IC50	3.1	nM	CHEMBL1257791
8.49	IC50	3.2	nM	CHEMBL1258590
8.48	IC50	3.3	nM	CHEMBL1258368
8.40	IC50	4	nM	CHEMBL1257668
8.35	IC50	4.5	nM	CHEMBL1257792
8.33	IC50	4.7	nM	CHEMBL1258020
8.31	IC50	4.9	nM	CHEMBL1258019
8.30	IC50	5	nM	CHEMBL211177
8.30	IC50	5	nM	CHEMBL209844
8.29	IC50	5.1	nM	CHEMBL1258700
8.24	IC50	5.7	nM	CHEMBL1258701
8.17	IC50	6.7	nM	CHEMBL1258481
8.15	IC50	7	nM	CHEMBL208825
8.15	IC50	7	nM	CHEMBL209108
8.10	IC50	8	nM	CHEMBL400455
8.10	IC50	8	nM	CHEMBL380868
8.10	IC50	8	nM	CHEMBL378459
8.10	IC50	7.943	nM	CHEMBL400455
8.10	IC50	7.943	nM	CHEMBL380868
8.09	IC50	8.1	nM	CHEMBL1258137
8.06	IC50	8.7	nM	CHEMBL1258018
8.05	IC50	9	nM	CHEMBL208770
8.05	IC50	9	nM	CHEMBL210138
8.05	IC50	8.9	nM	CHEMBL1258366
8.00	IC50	10	nM	CHEMBL379321
7.96	IC50	11	nM	CHEMBL379161
7.96	IC50	11	nM	CHEMBL1258138

PubChem BioAssay actives

382 with measured affinity, of 439 total; 50 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-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-N,N-bis(2-methylpropyl)benzamide	261285: Inhibition of MCD	ic50	0.0001	uM
N-(2-cyanoethyl)-N-ethyl-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzamide	261285: Inhibition of MCD	ic50	0.0003	uM
3-[4-carbamoyl-1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidin-4-yl]benzoic acid	517536: Inhibition of human MCD	ic50	0.0005	uM
4-(3-carboxyphenyl)-1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid	517536: Inhibition of human MCD	ic50	0.0006	uM
[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-pyrrolidin-1-ylmethanone	261285: Inhibition of MCD	ic50	0.0008	uM
3-[1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidin-4-yl]benzoic acid	517536: Inhibition of human MCD	ic50	0.0009	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-N-methylsulfonyl-4-phenylpiperidine-4-carboxamide	517536: Inhibition of human MCD	ic50	0.0009	uM
[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-piperidin-1-ylmethanone	261285: Inhibition of MCD	ic50	0.0010	uM
N-benzyl-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-N-methylbenzamide	261285: Inhibition of MCD	ic50	0.0010	uM
[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-morpholin-4-ylmethanone	261285: Inhibition of MCD	ic50	0.0011	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-4-phenylpiperidine-4-carboxylic acid	517536: Inhibition of human MCD	ic50	0.0011	uM
3-[4-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperazin-1-yl]benzoic acid	517536: Inhibition of human MCD	ic50	0.0013	uM
4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-N-methoxy-N-methylbenzamide	261285: Inhibition of MCD	ic50	0.0014	uM
4-(4-fluorophenyl)-1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid	517536: Inhibition of human MCD	ic50	0.0014	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-[3-(2H-tetrazol-5-yl)phenyl]piperazin-1-yl]-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0016	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-(2-fluorophenyl)-4-(2H-tetrazol-5-yl)piperidin-1-yl]-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0016	uM
2-[1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidin-4-yl]benzoic acid	517536: Inhibition of human MCD	ic50	0.0017	uM
3-[1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidin-4-yl]benzamide	517536: Inhibition of human MCD	ic50	0.0018	uM
4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-N-methyl-N-(2-phenylethyl)benzamide	261285: Inhibition of MCD	ic50	0.0020	uM
3-[4-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperazin-1-yl]benzamide	517536: Inhibition of human MCD	ic50	0.0022	uM
3-[4-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperazin-1-yl]-N-methylbenzamide	517536: Inhibition of human MCD	ic50	0.0023	uM
4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-N-(2-phenylethyl)benzamide	261285: Inhibition of MCD	ic50	0.0027	uM
2-[2-[4-(4-aminophenyl)piperazin-1-yl]-1,3-thiazol-5-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol	517536: Inhibition of human MCD	ic50	0.0027	uM
3-[1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidin-4-yl]-N-methylbenzamide	517536: Inhibition of human MCD	ic50	0.0031	uM
2-[2-[4-(3-aminophenyl)piperazin-1-yl]-1,3-thiazol-5-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol	517536: Inhibition of human MCD	ic50	0.0032	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-4-phenyl-N-(2,2,2-trifluoroethyl)piperidine-4-carboxamide	517536: Inhibition of human MCD	ic50	0.0033	uM
4-[1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperidin-4-yl]benzoic acid	517536: Inhibition of human MCD	ic50	0.0040	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-4-phenylpiperidin-4-ol	517536: Inhibition of human MCD	ic50	0.0045	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-N-methyl-4-phenylpiperidine-4-carboxamide	517536: Inhibition of human MCD	ic50	0.0047	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-4-phenylpiperidine-4-carboxamide	517536: Inhibition of human MCD	ic50	0.0049	uM
3-methylpentan-3-yl (3S)-3-[[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]butanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0050	uM
tert-butyl (3S)-3-[[(5R)-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]butanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0050	uM
2-[4-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]piperazin-1-yl]benzoic acid	517536: Inhibition of human MCD	ic50	0.0051	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-(trifluoromethyl)phenyl]sulfonyl-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0057	uM
4-(2-amino-1,3-thiazol-4-yl)-7-[[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]sulfanyl]chromen-2-one	517536: Inhibition of human MCD	ic50	0.0067	uM
3-methylpentan-3-yl 3-[[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0070	uM
tert-butyl (3S)-3-[[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]butanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0070	uM
5-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-N-(2-methylpropanoyl)anilino]pentanoic acid	311036: Inhibition of human recombinant MCD	ic50	0.0079	uM
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-methyl-N-[4-(2H-tetrazol-5-yl)butyl]propanamide	311036: Inhibition of human recombinant MCD	ic50	0.0079	uM
tert-butyl (3R)-3-[[(5R)-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]butanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0080	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-(4-fluorophenyl)piperazin-1-yl]-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0081	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-(3-fluorophenyl)piperazin-1-yl]-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0087	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-(4-nitrophenyl)piperazin-1-yl]-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0089	uM
N-[(4-cyanophenyl)methyl]-N-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]pyridine-4-carboxamide	267728: Inhibition of MCD	ic50	0.0090	uM
2,4,6-trimethylheptan-4-yl 3-[[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0090	uM
tert-butyl (3R)-3-[[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]butanoate	268132: Inhibition of malonyl-coenzyme A decarboxylase	ic50	0.0100	uM
4-[[(3,5-dichlorobenzoyl)-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]amino]methyl]benzoic acid	267728: Inhibition of MCD	ic50	0.0110	uM
1,1,1,3,3,3-hexafluoro-2-[2-[4-(3-fluorophenyl)piperidin-1-yl]-1,3-thiazol-5-yl]propan-2-ol	517536: Inhibition of human MCD	ic50	0.0110	uM
1-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-4-phenylpiperidine-4-carbonitrile	517536: Inhibition of human MCD	ic50	0.0110	uM
2-[2-[4-(3,4-difluorophenyl)piperazin-1-yl]-1,3-thiazol-5-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol	517536: Inhibition of human MCD	ic50	0.0110	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Leflunomide	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-thujone	affects cotreatment, increases expression	1
spathulenol	affects cotreatment, increases expression	1
linalool	affects cotreatment, increases expression	1
caryophyllene	affects cotreatment, increases expression	1
sabinene	affects cotreatment, increases expression	1
linalyl acetate	affects cotreatment, increases expression	1
fipronil	increases expression	1
myrcene	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
Eucalyptol	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases expression	1
Camphor	affects cotreatment, increases expression	1
Phenobarbital	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 8 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1261133	Binding	Inhibition of human MCD	Design and synthesis of a new class of malonyl-CoA decarboxylase inhibitors with anti-obesity and anti-diabetic activities. — Bioorg Med Chem Lett
CHEMBL859666	Functional	Glucose oxidation rate in isolated working hearts of Sprague-Dawley rat at 20 uM relative to DMSO	Synthesis and structure-activity relationship of small-molecule malonyl coenzyme A decarboxylase inhibitors. — J Med Chem

Clinical trials (associated diseases)

200 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01289158	Not specified	UNKNOWN	Combined Malonic and Methylmalonic Aciduria (CMAMMA): Gene Identification and Outcome Study
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)