BCKDK

Summary

BCKDK (branched chain keto acid dehydrogenase kinase, HGNC:16902) is a protein-coding gene on chromosome 16p11.2, encoding Branched-chain alpha-ketoacid dehydrogenase kinase (O14874). Serine/threonine-protein kinase component of macronutrients metabolism.

The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCKD. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10295 — RefSeq curated summary.

At a glance

• Gene–disease (curated): branched-chain keto acid dehydrogenase kinase deficiency (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 203 total — 9 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes
• MANE Select transcript: NM_005881

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16902
Approved symbol	BCKDK
Name	branched chain keto acid dehydrogenase kinase
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000103507
Ensembl biotype	protein_coding
OMIM	614901
Entrez	10295

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 21 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000219794, ENST00000287507, ENST00000394950, ENST00000394951, ENST00000484226, ENST00000561755, ENST00000566568, ENST00000567530, ENST00000567676, ENST00000567682, ENST00000859428, ENST00000859429, ENST00000859430, ENST00000859431, ENST00000859432, ENST00000859433, ENST00000859434, ENST00000859435, ENST00000859436, ENST00000859437, ENST00000913319, ENST00000950482, ENST00000950483

RefSeq mRNA: 3 — MANE Select: NM_005881 NM_001122957, NM_001271926, NM_005881

CCDS: CCDS10705, CCDS45467, CCDS61917

Canonical transcript exons

ENST00000219794 — 12 exons

Exon	Start	End
ENSE00000675921	31109673	31109783
ENSE00000675922	31110077	31110124
ENSE00000675924	31110401	31110499
ENSE00001599140	31110688	31110761
ENSE00002616272	31112121	31112791
ENSE00003578839	31111091	31111219
ENSE00003580852	31110205	31110324
ENSE00003611028	31109047	31109418
ENSE00003629043	31111300	31111389
ENSE00003641548	31111869	31112027
ENSE00003790585	31109511	31109579
ENSE00003847144	31108386	31108479

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 96.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.6009 / max 314.0134, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153767	66.7340	1822
153768	0.8669	583

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.36	gold quality
right adrenal gland	UBERON:0001233	95.08	gold quality
right adrenal gland cortex	UBERON:0035827	94.94	gold quality
body of pancreas	UBERON:0001150	94.79	gold quality
left adrenal gland	UBERON:0001234	94.64	gold quality
left adrenal gland cortex	UBERON:0035825	94.39	gold quality
gastrocnemius	UBERON:0001388	94.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.26	gold quality
heart left ventricle	UBERON:0002084	94.20	gold quality
parotid gland	UBERON:0001831	93.87	gold quality
right lobe of liver	UBERON:0001114	93.86	gold quality
cardiac ventricle	UBERON:0002082	93.68	gold quality
muscle of leg	UBERON:0001383	93.66	gold quality
right atrium auricular region	UBERON:0006631	93.24	gold quality
body of stomach	UBERON:0001161	93.17	gold quality
skin of leg	UBERON:0001511	92.92	gold quality
skin of abdomen	UBERON:0001416	92.72	gold quality
adrenal cortex	UBERON:0001235	92.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.50	gold quality
lower esophagus	UBERON:0013473	92.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.42	gold quality
adrenal gland	UBERON:0002369	92.17	gold quality
left coronary artery	UBERON:0001626	92.13	gold quality
mucosa of transverse colon	UBERON:0004991	91.91	gold quality
heart	UBERON:0000948	91.73	gold quality
saliva-secreting gland	UBERON:0001044	91.63	gold quality
metanephros cortex	UBERON:0010533	91.63	gold quality
minor salivary gland	UBERON:0001830	91.62	gold quality
stromal cell of endometrium	CL:0002255	91.58	gold quality
granulocyte	CL:0000094	91.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	40.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting BCKDK, 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-4698	99.84	71.41	4303
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4761-3P	96.27	66.26	524

Literature-anchored findings (GeneRIF, showing 9)

• employment of multidimensional heteronuclear NMR techniques to determine the structure and dynamics of the LBD of the human branched-chain alpha-keto acid dehydrogenase complex (hbLBD) (PMID:11839747)
• This publication is about the mouse gene but contains the 5’ sequence of the human gene, including upstream open reading frame information. (PMID:15302860)
• Results demonstrate that BCKDK mutations can result in neurobehavioral deficits in humans. (PMID:24449431)
• There is a relationship between plamsa CST and BCKDK in sepsis patients. (PMID:27773658)
• our study indicates that BCKDK promotes colorectal tumorigenesis through up-regulation of the MAPK signaling pathway by phosphorylating MEK at Ser221. (PMID:28501528)
• Phosphorylation of BCKDK of BCAA catabolism at Y246 by Src promotes metastasis of colorectal cancer. (PMID:32238881)
• APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway. (PMID:32457292)
• BCKDK regulates breast cancer cell adhesion and tumor metastasis by inhibiting TRIM21 ubiquitinate talin1. (PMID:37460470)
• Cross-talk between BCKDK-mediated phosphorylation and STUB1-dependent ubiquitination degradation of BCAT1 promotes GBM progression. (PMID:38621458)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bckdk	ENSDARG00000016904
mus_musculus	Bckdk	ENSMUSG00000030802
rattus_norvegicus	Bckdk	ENSRNOG00000077965

Paralogs (4): PDK4 (ENSG00000004799), PDK2 (ENSG00000005882), PDK3 (ENSG00000067992), PDK1 (ENSG00000152256)

Protein

Protein identifiers

Branched-chain alpha-ketoacid dehydrogenase kinase — O14874 (reviewed: O14874)

Alternative names: [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial

All UniProt accessions (6): O14874, H3BNP3, H3BQP2, H3BS02, H3BTL2, H3BUV3

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle. Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex. Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively. Recognizes phosphosites having SxxE/D canonical motif.

Subunit / interactions. Homodimer. Homotetramer. Dimerizes through interaction of two opposing nucleotide-binding domains. Interacts with E2 component of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. Competes with BCKDK for binding to the E2 component; this interaction is modulated by branched-chain alpha-keto acids. At steady state, BCKDH holoenzyme contains BCKDK and BCKDHA is phosphorylated. In response to high levels of branched-chain alpha-keto acids, the inhibitory BCKDK is replaced by activating PPM1K leading to BCKDHA dephosphorylation and BCAA degradation.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Ubiquitous.

Post-translational modifications. Autophosphorylated.

Disease relevance. Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) [MIM:614923] A metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids. The disease is caused by variants affecting the gene represented in this entry. A diet enriched in branched amino acids (BCAAs) allows to normalize plasma BCAA levels. This suggests that it may be possible to treat patients with mutations in BCKDK with BCAA supplementation.

Activity regulation. Allosterically inhibited by certain thiazoles and thiophenes: thiazoles increase interaction with DBT/BCKDH-E2, whereas thiophenes reduce this interaction. Inhibited by 3,6- dichlorobenzo[b]thiophene-2-carboxylic acid (BT2). The ATP binding is mediated by both potassium and magnesium ions.

Pathway. Protein modification.

Similarity. Belongs to the PDK/BCKDK protein kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14874-1	1	yes
O14874-2	2
O14874-3	3

RefSeq proteins (3): NP_001116429, NP_001258855, NP_005872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003594	HATPase_dom	Domain
IPR004358	Sig_transdc_His_kin-like_C	Domain
IPR005467	His_kinase_dom	Domain
IPR018955	BCDHK/PDK_N	Domain
IPR036784	AK/P_DHK_N_sf	Homologous_superfamily
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR039028	BCKD/PDK	Family

Pfam: PF02518, PF10436

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[3-methyl-2-oxobutanoate dehydrogenase] + ATP = O-phospho-L-seryl-[3-methyl-2-oxobutanoate dehydrogenase] + ADP + H(+) (RHEA:17301)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)

UniProt features (56 total): binding site 12, helix 12, strand 9, modified residue 6, turn 5, sequence conflict 4, sequence variant 3, splice variant 2, transit peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9DI9	X-RAY DIFFRACTION	2.15
8F5J	X-RAY DIFFRACTION	2.54
7ZPE	X-RAY DIFFRACTION	2.64
8F5S	X-RAY DIFFRACTION	2.79
8F5F	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14874-F1	84.03	0.68

Functional residue map

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

Ligand- & substrate-binding residues (12): 335; 364; 367; 367; 370; 279; 279; 315; 328; 330; 333; 334

Post-translational modifications (6): 31, 52, 192, 233, 356, 360

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-9912481	Branched-chain ketoacid dehydrogenase kinase deficiency
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-5668914	Diseases of metabolism
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-9865118	Diseases of branched-chain amino acid catabolism

MSigDB gene sets: 307 (showing top): RRAGTTGT_UNKNOWN, LU_IL4_SIGNALING, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, AACWWCAANK_UNKNOWN, NFKB_Q6, GOBP_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS

GO Biological Process (10): L-isoleucine catabolic process (GO:0006550), L-leucine catabolic process (GO:0006552), L-valine catabolic process (GO:0006574), spermatogenesis (GO:0007283), lipid biosynthetic process (GO:0008610), amino acid catabolic process (GO:0009063), branched-chain amino acid catabolic process (GO:0009083), regulation of pyruvate decarboxylation to acetyl-CoA (GO:0010510), regulation of glucose metabolic process (GO:0010906), phosphorylation (GO:0016310)

GO Molecular Function (13): protein serine/threonine kinase activity (GO:0004674), protein serine/threonine phosphatase activity (GO:0004722), pyruvate dehydrogenase (acetyl-transferring) kinase activity (GO:0004740), ATP binding (GO:0005524), kinase activity (GO:0016301), [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity (GO:0047323), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740), transferase activity, transferring phosphorus-containing groups (GO:0016772), catalytic activity, acting on a protein (GO:0140096)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), oxoglutarate dehydrogenase complex (GO:0045252)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Diseases of branched-chain amino acid catabolism	1
Disease	1
Metabolism	1
Diseases of metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
branched-chain amino acid catabolic process	3
L-amino acid catabolic process	3
proteinogenic amino acid catabolic process	3
protein kinase activity	2
protein serine/threonine kinase activity	2
catalytic activity	2
L-leucine metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
lipid metabolic process	1
biosynthetic process	1
amino acid metabolic process	1
catabolic process	1
amino acid catabolic process	1
branched-chain amino acid metabolic process	1
carboxylic acid catabolic process	1
pyruvate decarboxylation to acetyl-CoA	1
regulation of acyl-CoA biosynthetic process	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
tricarboxylic acid cycle heteromeric enzyme complex	1
alpha-ketoacid dehydrogenase complex	1
transferase complex	1

Protein interactions and networks

STRING

3472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCKDK	PPM1K	Q8N3J5	789
BCKDK	BCKDHA	P12694	768
BCKDK	BCAT2	O15382	729
BCKDK	BCKDHB	P21953	643
BCKDK	BCAT1	P54687	583
BCKDK	CHD8	Q9HCK8	543
BCKDK	J3KPS3	J3KPS3	537
BCKDK	ALDOA	P04075	535
BCKDK	MAP4K1	Q92918	532
BCKDK	MCCC1	Q96RQ3	486
BCKDK	AARS2	Q5JTZ9	477
BCKDK	GCDH	Q92947	473
BCKDK	PKM	P14618	467
BCKDK	NUDT22	Q9BRQ3	462
BCKDK	ETFB	P38117	461

IntAct

107 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
METTL21C	BCKDK	psi-mi:“MI:0915”(physical association)	0.640
BCKDK	CETN3	psi-mi:“MI:0914”(association)	0.640
METTL21C	BCKDK	psi-mi:“MI:0914”(association)	0.640
	BCKDK	psi-mi:“MI:0915”(physical association)	0.560
BCKDK		psi-mi:“MI:0915”(physical association)	0.560
BCKDK	SPTA1	psi-mi:“MI:0915”(physical association)	0.560
GCNT3	BCKDK	psi-mi:“MI:0914”(association)	0.530
rep	SBNO1	psi-mi:“MI:0914”(association)	0.530
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
STAT3	BCKDK	psi-mi:“MI:0915”(physical association)	0.510
BCKDK	STAT3	psi-mi:“MI:0915”(physical association)	0.510
BCKDK		psi-mi:“MI:0915”(physical association)	0.510

BioGRID (177): BCKDK (Affinity Capture-MS), CETN3 (Affinity Capture-MS), WDTC1 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), BCKDK (Affinity Capture-MS), BCKDK (Affinity Capture-MS), BCKDK (Affinity Capture-MS), BCKDK (Affinity Capture-MS), BCKDK (Affinity Capture-MS), LGALS3BP (Affinity Capture-MS), CETN3 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), BCKDK (Affinity Capture-MS), WDTC1 (Affinity Capture-MS), BCKDK (Affinity Capture-MS)

ESM2 similar proteins: B6JWC1, B9FK36, O01757, O02623, O14874, O42895, O54937, O55028, O70571, O88345, P36617, P37221, P37224, P37225, P39864, P40530, P48009, P78820, P78875, P78963, P91622, Q00972, Q02332, Q09116, Q10299, Q15118, Q15119, Q15120, Q16654, Q17828, Q1KMR4, Q2KJG8, Q38970, Q61SU7, Q63065, Q64536, Q8BFP9, Q8S6N5, Q922H2, Q9BGQ3

Diamond homologs: O02623, O14874, O54937, O55028, O70571, O88345, P91622, Q00972, Q02332, Q15118, Q15119, Q15120, Q16654, Q1KMR4, Q2KJG8, Q63065, Q64536, Q8BFP9, Q922H2, Q9JK42, Q9P6P9, Q9SBJ1, Q9RDT3, A5INR0, A6QD58, A6TXG9, A7WWQ7, A8YYU2, Q2FKN7, Q2G2U4, Q2YUQ2, Q4LAJ8, Q5HJX6, Q5HK19, Q6GD71, Q6GKS6, Q7A215, Q7A305, Q7A8E0, Q8CU87

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
BCKDK	down-regulates	BCKDHA	phosphorylation
SRC	“up-regulates activity”	BCKDK	phosphorylation
SRC	“up-regulates quantity by stabilization”	BCKDK	phosphorylation
BCKDK	“up-regulates activity”	ACLY	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	9
Uncertain significance	96
Likely benign	62
Benign	6

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1285549	NM_005881.4(BCKDK):c.50_71del (p.Leu17fs)	Pathogenic
2691734	NM_005881.4(BCKDK):c.264+1G>C	Pathogenic
3391930	GRCh37/hg19 16p11.2(chr16:30907349-31334236)x1	Pathogenic
39743	NM_005881.4(BCKDK):c.466C>T (p.Arg156Ter)	Pathogenic
39744	NM_005881.4(BCKDK):c.222del (p.Met74fs)	Pathogenic
39745	NM_005881.4(BCKDK):c.671G>C (p.Arg224Pro)	Pathogenic
4294340	NM_005881.4(BCKDK):c.355_356insC (p.Asn119fs)	Pathogenic
4294342	NC_000016.10:g.31108386_31112801del	Pathogenic
4704718	NM_005881.4(BCKDK):c.453C>A (p.Tyr151Ter)	Pathogenic
1526506	GRCh37/hg19 16p11.2(chr16:30943854-31171177)	Likely pathogenic
1690662	NM_005881.4(BCKDK):c.879C>A (p.Tyr293Ter)	Likely pathogenic
2430650	NM_005881.4(BCKDK):c.433C>T (p.Gln145Ter)	Likely pathogenic
2500177	NM_005881.4(BCKDK):c.979C>T (p.Arg327Trp)	Likely pathogenic
4086232	NM_005881.4(BCKDK):c.543+1G>A	Likely pathogenic
4280147	NM_005881.4(BCKDK):c.1165_1220del (p.Leu389fs)	Likely pathogenic
4294341	NM_005881.4(BCKDK):c.936G>C (p.Arg312Ser)	Likely pathogenic
434505	NM_005881.4(BCKDK):c.453C>G (p.Tyr151Ter)	Likely pathogenic
996751	NM_005881.4(BCKDK):c.646_649del (p.Asp216fs)	Likely pathogenic

SpliceAI

1682 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31109415:GAAG:G	donor_gain	1.0000
16:31109416:AAGG:A	donor_loss	1.0000
16:31109417:AGG:A	donor_loss	1.0000
16:31109418:GGTG:G	donor_loss	1.0000
16:31109419:G:GG	donor_gain	1.0000
16:31109428:G:GT	donor_gain	1.0000
16:31109509:A:AG	acceptor_gain	1.0000
16:31109510:G:GG	acceptor_gain	1.0000
16:31109510:GC:G	acceptor_gain	1.0000
16:31109510:GCC:G	acceptor_gain	1.0000
16:31109510:GCCC:G	acceptor_gain	1.0000
16:31109510:GCCCT:G	acceptor_gain	1.0000
16:31109580:G:GG	donor_gain	1.0000
16:31109669:CCAG:C	acceptor_loss	1.0000
16:31109671:A:AG	acceptor_gain	1.0000
16:31109672:G:GA	acceptor_loss	1.0000
16:31109672:G:GG	acceptor_gain	1.0000
16:31109672:GA:G	acceptor_gain	1.0000
16:31109672:GAAA:G	acceptor_gain	1.0000
16:31109672:GAAAA:G	acceptor_gain	1.0000
16:31109781:GTG:G	donor_gain	1.0000
16:31110075:A:AG	acceptor_gain	1.0000
16:31110075:AGCAT:A	acceptor_gain	1.0000
16:31110076:G:GA	acceptor_gain	1.0000
16:31110076:GC:G	acceptor_gain	1.0000
16:31110076:GCATG:G	acceptor_gain	1.0000
16:31110125:G:GG	donor_gain	1.0000
16:31110201:GCAG:G	acceptor_loss	1.0000
16:31110202:CA:C	acceptor_loss	1.0000
16:31110203:A:AG	acceptor_gain	1.0000

AlphaMissense

2680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31109748:T:C	F114L	1.000
16:31109750:C:A	F114L	1.000
16:31109750:C:G	F114L	1.000
16:31110295:G:C	G172R	1.000
16:31111123:C:A	P250H	1.000
16:31111201:T:C	L276P	1.000
16:31111206:A:G	K278E	1.000
16:31111208:G:C	K278N	1.000
16:31111208:G:T	K278N	1.000
16:31111876:G:C	D315H	1.000
16:31112126:G:A	G367D	1.000
16:31112132:G:A	G369E	1.000
16:31109701:T:C	L98P	0.999
16:31109716:C:A	A103D	0.999
16:31109749:T:C	F114S	0.999
16:31109773:T:A	I122K	0.999
16:31109773:T:G	I122R	0.999
16:31109776:T:C	L123P	0.999
16:31110287:T:C	L169S	0.999
16:31110296:G:A	G172D	0.999
16:31110438:T:C	L194P	0.999
16:31110447:G:T	R197M	0.999
16:31110459:G:C	R201P	0.999
16:31110700:G:C	G219R	0.999
16:31110701:G:A	G219D	0.999
16:31110701:G:T	G219V	0.999
16:31111098:T:C	C242R	0.999
16:31111099:G:A	C242Y	0.999
16:31111100:T:G	C242W	0.999
16:31111123:C:G	P250R	0.999

dbSNP variants (sampled 300 via entrez): RS1000243212 (16:31115669 G>A), RS1000478853 (16:31114704 T>A,C), RS1000654361 (16:31116639 GGGCACGGT>G), RS1000720645 (16:31115397 A>C), RS1000984143 (16:31117000 G>T), RS1001117994 (16:31118114 C>G,T), RS1001187935 (16:31114990 T>A,C), RS1001232586 (16:31117808 C>T), RS1001676990 (16:31116232 G>A,T), RS1002045092 (16:31117318 G>A,T), RS1002056919 (16:31109863 C>A,G,T), RS1002117247 (16:31117093 C>G,T), RS1002123246 (16:31113648 A>G), RS1002358085 (16:31111493 A>C,G), RS1002772744 (16:31110862 T>C)

Disease associations

OMIM: gene MIM:614901 | disease phenotypes: MIM:614923, MIM:615135, MIM:618974, MIM:248600

GenCC curated gene-disease

Disease	Classification	Inheritance
branched-chain keto acid dehydrogenase kinase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
branched-chain keto acid dehydrogenase kinase deficiency	Definitive	AR

Mondo (6): branched-chain keto acid dehydrogenase kinase deficiency (MONDO:0013970), breast ductal adenocarcinoma (MONDO:0005590), maple syrup urine disease, mild variant (MONDO:0014057), Li-Ghorbani-Weisz-Hubshman syndrome (MONDO:0033547), maple syrup urine disease type 1A (MONDO:0023691), intellectual disability (MONDO:0001071)

Orphanet (3): Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency (Orphanet:308410), Maple syrup urine disease (Orphanet:511), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000293	Full cheeks
HP:0000350	Small forehead
HP:0000407	Sensorineural hearing impairment
HP:0000422	Abnormal nasal bridge morphology
HP:0000518	Cataract
HP:0000711	Restlessness
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000958	Dry skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001271	Polyneuropathy
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001999	Abnormal facial shape
HP:0002069	Bilateral tonic-clonic seizure
HP:0002123	Generalized myoclonic seizure
HP:0002197	Generalized-onset seizure
HP:0002208	Coarse hair

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002544_4	Parkinson’s disease	2.000000e-12
GCST008103_175	Bipolar disorder	8.000000e-06
GCST008115_45	Bipolar I disorder	5.000000e-07
GCST010659_21	Waist circumference	4.000000e-15
GCST010660_5	Triglyceride levels	4.000000e-06
GCST010662_12	Systolic blood pressure	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4879410 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9923231	BCKDK, PRSS53, VKORC1	1A	484.38	9	warfarin;acenocoumarol;phenprocoumon
rs61162043	BCKDK, VKORC1	3	2.75	1	warfarin

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Pyruvate dehydrogenase kinase (PDHK) family

Binding affinities (BindingDB)

158 measured of 159 human assays (159 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(6-chloro-2,4-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid, ATROP-2	IC50	4 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(6-chloro-2,4-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	4.2 nM	US-12466803: BCKDK inhibitors and/or degraders
ammonium 3-(3-ethyl-2,4,5-trifluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylate	IC50	6.7 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(3-Chloro-2,4,5-trifluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	7.4 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(2,4,6-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	7.6 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Fluoro-3-(2,4,6-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	10 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Chloro-3-(2,4-difluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	11 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(4-chloro-2,6-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	11 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(4-chloro-2-fluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	12 nM	US-12466803: BCKDK inhibitors and/or degraders
Ammonium 6-chloro-3-(2,4,5-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylate	IC50	12.1 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(3-ethyl-2,4,5-trifluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	13 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Fluoro-3-(2,4,5-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	15 nM	US-12466803: BCKDK inhibitors and/or degraders
ammonium 6-chloro-3-(5-chloro-2,4-difluorophenyl)-1-benzothiophene-2-carboxylate	IC50	15 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(2,4-difluoro-3-methylphenyl)-1-benzothiophene-2-carboxylic acid	IC50	15 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(3-ethyl-2,4-difluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	16 nM	US-12466803: BCKDK inhibitors and/or degraders
ammonium 6-chloro-3-(2,3,4,5-tetrafluorophenyl)-1-benzothiophene-2-carboxylate	IC50	16 nM	US-12466803: BCKDK inhibitors and/or degraders
ammonium 6-chloro-3-(4-chloro-2,5-difluoro-3-methylphenyl)-1-benzothiophene-2-carboxylate	IC50	17 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(3-cyclopropyl-2,4-difluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	17 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(5-chloro-2,4-difluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	18 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(4-chloro-2-fluoro-3-methylphenyl)-1-benzothiophene-2-carboxylic acid	IC50	18 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2,4-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	20 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(3-ethyl-2,4-difluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	20 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2,4,5-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	21 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Chloro-3-(2,4,5-trifluoro-3-methylphenyl)-1-benzothiophene-2-carboxylic acid	IC50	22 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(4,5-Dichloro-2-fluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	24 nM	US-12466803: BCKDK inhibitors and/or degraders
6-fluoro-3-(2,3,4,5-tetrafluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	24 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2,4-difluoro-3-methylphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	24 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(4-chloro-2-fluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	26 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Chloro-3-(2,4,5-trifluoro-3-methoxyphenyl)-1-benzofuran-2-carboxylic acid	IC50	28 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Fluoro-3-(2,4,5-trifluoro-3-methoxyphenyl)-1-benzofuran-2-carboxylic acid	IC50	33 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(2,4-difluoro-5-methylphenyl)-1-benzothiophene-2-carboxylic acid	IC50	33 nM	US-12466803: BCKDK inhibitors and/or degraders
6-fluoro-3-(2,3,5,6-tetrafluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	33 nM	US-12466803: BCKDK inhibitors and/or degraders
6-Fluoro-3-(2,4,5-trifluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	34 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2-chloro-4,6-difluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	36 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(3-chloro-2,6-difluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	37 nM	US-12466803: BCKDK inhibitors and/or degraders
6-fluoro-3-(2,4,5-trifluoro-3-methylphenyl)-1-benzothiophene-2-carboxylic acid	IC50	41 nM	US-12466803: BCKDK inhibitors and/or degraders
6-fluoro-3-(2,4,6-trifluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	46 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(2,4,5-trifluorophenyl)-1-benzothiophene-2-carboxylic acid	IC50	47 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(6-chloro-2-fluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	47 nM	US-12466803: BCKDK inhibitors and/or degraders
ammonium 6-chloro-3-(4-chloro-2-fluoro-5-methylphenyl)-1-benzothiophene-2-carboxylate	IC50	50 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(4-cyano-2,6-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	56 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(4-chloro-2-fluoro-3-methylphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	59 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(4-chloro-2-fluoro-5-methylphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	59 nM	US-12466803: BCKDK inhibitors and/or degraders
6-chloro-3-(2,6-difluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid	IC50	74 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2,6-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	78 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2,5-dichloro-3-fluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	82 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2,4-difluoro-5-methylphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	93 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(5,7-Difluoro-3,4-dihydro-2H-1-benzopyran-6-yl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	110 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(3-chloro-2-fluoro-4-methylphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	110 nM	US-12466803: BCKDK inhibitors and/or degraders
3-(2-chloro-4,6-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid	IC50	110 nM	US-12466803: BCKDK inhibitors and/or degraders

ChEMBL bioactivities

53 potent at pChembl≥5 of 61 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.32	Kd	4.8	nM	CHEMBL6143249
8.22	IC50	6	nM	CHEMBL6102266
8.17	IC50	6.7	nM	CHEMBL6173779
8.00	IC50	10	nM	CHEMBL6162740
7.82	IC50	15	nM	CHEMBL6143249
7.70	IC50	20	nM	CHEMBL6177075
7.47	IC50	34	nM	CHEMBL6172636
7.39	IC50	41	nM	CHEMBL6173277
7.34	IC50	46	nM	CHEMBL6143249
7.22	IC50	60	nM	CHEMBL6173779
7.17	IC50	67	nM	CHEMBL6162740
6.96	IC50	110	nM	CHEMBL6171670
6.68	IC50	210	nM	CHEMBL6177075
6.64	IC50	230	nM	CHEMBL6074548
6.62	IC50	240	nM	CHEMBL6173277
6.42	IC50	380	nM	CHEMBL6074548
6.33	IC50	470	nM	CHEMBL6078430
6.32	Kd	480	nM	CHEMBL6074548
6.31	IC50	490	nM	CHEMBL6166381
6.27	IC50	540	nM	CHEMBL6171670
6.24	IC50	580	nM	CHEMBL6078430
6.22	IC50	600	nM	CHEMBL6091967
6.22	Kd	600	nM	CHEMBL6091967
6.12	IC50	750	nM	CHEMBL6091967
6.10	IC50	800	nM	CHEMBL6150712
6.06	IC50	880	nM	CHEMBL6078439
6.05	IC50	900	nM	CHEMBL6171147
6.04	IC50	920	nM	CHEMBL5281064
6.02	IC50	950	nM	CHEMBL6172636
6.00	IC50	1000	nM	CHEMBL6083170
5.96	IC50	1100	nM	CHEMBL1448105
5.89	IC50	1300	nM	CHEMBL6101895
5.89	IC50	1300	nM	CHEMBL6103238
5.89	IC50	1300	nM	CHEMBL6170584
5.85	IC50	1400	nM	CHEMBL6078129
5.82	IC50	1500	nM	CHEMBL6103476
5.80	IC50	1600	nM	CHEMBL6078430
5.80	IC50	1600	nM	CHEMBL6078437
5.72	IC50	1900	nM	CHEMBL6102462
5.64	IC50	2300	nM	CHEMBL6074439
5.58	IC50	2600	nM	CHEMBL6120618
5.58	IC50	2600	nM	CHEMBL6102382
5.54	IC50	2900	nM	CHEMBL6102939
5.51	IC50	3100	nM	CHEMBL6150712
5.41	IC50	3900	nM	CHEMBL1448105
5.25	IC50	5600	nM	CHEMBL5281064
5.25	IC50	5600	nM	CHEMBL6170584
5.23	IC50	5900	nM	CHEMBL6083088
5.20	IC50	6300	nM	CHEMBL6133889
5.17	IC50	6800	nM	CHEMBL6074606

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
daidzein	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
daidzin	affects cotreatment, decreases expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
genistin	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
glycitein	affects cotreatment, decreases expression	1
glycitin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arbutin	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Bucladesine	affects cotreatment, increases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4824991	Binding	Inhibition of human recombinant BCKDK incubated for 60 mins by ADP-Glo kinase assay	Fragment-based lead discovery to identify novel inhibitors that target the ATP binding site of pyruvate dehydrogenase kinases. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SE86	HAP1 BCKDK (-)	Cancer cell line	Male

Clinical trials (associated diseases)

209 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
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
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
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
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)
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
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
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