KDM5C

Summary

KDM5C (lysine demethylase 5C, HGNC:11114) is a protein-coding gene on chromosome Xp11.22, encoding Lysine-specific demethylase 5C (P41229). Histone demethylase that specifically demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. Mutations in this gene have been associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8242 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,197 total — 102 pathogenic, 83 likely-pathogenic
• Phenotypes (HPO): 68
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 7 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_004187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11114
Approved symbol	KDM5C
Name	lysine demethylase 5C
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	DXS1272E, XE169
Ensembl gene	ENSG00000126012
Ensembl biotype	protein_coding
OMIM	314690
Entrez	8242

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 16 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000349663, ENST00000375379, ENST00000375383, ENST00000375401, ENST00000404049, ENST00000428012, ENST00000429877, ENST00000452825, ENST00000465402, ENST00000467093, ENST00000477109, ENST00000481369, ENST00000495519, ENST00000497100, ENST00000497995, ENST00000685423, ENST00000685539, ENST00000685641, ENST00000687695, ENST00000687928, ENST00000688699, ENST00000691505, ENST00000693277, ENST00000861450, ENST00000861451, ENST00000861452, ENST00000861453, ENST00000861454, ENST00000935430, ENST00000935431

RefSeq mRNA: 8 — MANE Select: NM_004187 NM_001146702, NM_001282622, NM_001353978, NM_001353979, NM_001353981, NM_001353982, NM_001353984, NM_004187

CCDS: CCDS14351, CCDS55417, CCDS65269, CCDS87747, CCDS94610, CCDS94611

Canonical transcript exons

ENST00000375401 — 26 exons

Exon	Start	End
ENSE00000000310	53224740	53225207
ENSE00000860394	53215795	53215976
ENSE00000860395	53214689	53214847
ENSE00000860397	53211497	53211655
ENSE00000860404	53198490	53198637
ENSE00000860405	53197771	53197876
ENSE00000860406	53196686	53197044
ENSE00000860410	53194139	53194738
ENSE00000860411	53193773	53193851
ENSE00001466943	53192158	53193332
ENSE00001605274	53194931	53195068
ENSE00001614347	53198764	53198888
ENSE00001636291	53217143	53217277
ENSE00001667228	53195231	53195410
ENSE00001690780	53195916	53196054
ENSE00001691478	53217796	53217966
ENSE00001764157	53193437	53193636
ENSE00001774049	53211787	53211906
ENSE00003467496	53218276	53218398
ENSE00003509543	53210414	53210576
ENSE00003537132	53201550	53201744
ENSE00003568454	53201854	53201973
ENSE00003598899	53216074	53216197
ENSE00003634992	53198977	53199158
ENSE00003648103	53220839	53220916
ENSE00003671874	53210676	53210857

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.4394 / max 169.7409, expressed in 1816 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199323	33.4394	1816

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.91	gold quality
stromal cell of endometrium	CL:0002255	95.85	gold quality
right uterine tube	UBERON:0001302	95.65	gold quality
body of uterus	UBERON:0009853	95.23	gold quality
lower esophagus mucosa	UBERON:0035834	95.22	gold quality
left ovary	UBERON:0002119	95.05	gold quality
granulocyte	CL:0000094	95.03	gold quality
right ovary	UBERON:0002118	94.84	gold quality
ectocervix	UBERON:0012249	94.80	gold quality
skin of leg	UBERON:0001511	94.60	gold quality
skin of abdomen	UBERON:0001416	94.39	gold quality
endometrium epithelium	UBERON:0004811	94.14	gold quality
endocervix	UBERON:0000458	94.02	gold quality
left uterine tube	UBERON:0001303	93.91	gold quality
mucosa of stomach	UBERON:0001199	93.88	gold quality
smooth muscle tissue	UBERON:0001135	93.82	gold quality
lymph node	UBERON:0000029	93.58	gold quality
gastrocnemius	UBERON:0001388	93.53	gold quality
vagina	UBERON:0000996	93.52	gold quality
cortical plate	UBERON:0005343	93.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.34	gold quality
minor salivary gland	UBERON:0001830	93.32	gold quality
cerebellar hemisphere	UBERON:0002245	93.26	gold quality
cerebellar cortex	UBERON:0002129	93.22	gold quality
tongue squamous epithelium	UBERON:0006919	93.20	silver quality
right lobe of thyroid gland	UBERON:0001119	93.17	gold quality
muscle of leg	UBERON:0001383	93.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.11	gold quality
olfactory bulb	UBERON:0002264	93.08	silver quality
left lobe of thyroid gland	UBERON:0001120	93.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.97
E-MTAB-6058	no	108.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
BDNF	Repression
EHMT2
EP400
FGFR1
HTT
KDM5C
KRT9
MBD2
ME3
PTEN	Repression
RRP8
SCN2A	Repression
SYN1	Repression

Upstream regulators (CollecTRI, top): ARX, BRD4, EPAS1, HIF1A, KDM5C, MBD2, PHF8, ZNF711

miRNA regulators (miRDB)

125 targeting KDM5C, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6785-5P	99.82	68.68	4428

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• JARID1C may have a role in X-Linked Mental Retardation (PMID:16538222)
• JARID1C appears to be one of the more frequently mutated genes in X-linked mental retardation. (PMID:16541399)
• We show that the X-linked mental retardation gene SMCX, which encodes a JmjC-domain protein, reversed histone H3 lysine 4 to di- and mono- but not unmethylated products. (PMID:17320160)
• has H3K4 tri-demethylase activity; functions as transcriptional repressor; loss of JARID1C/SMCX activity impairs REST-mediated neuronal gene regulation, thereby contributing to SMCX-associated X-linked mental retardation (PMID:17468742)
• Thus, SMCX is a novel Smad3 corepressor that may antagonize the tumor suppressing activity of the TGF-beta/Smad3 signaling pathway and thereby contribute to tumorigenesis. (PMID:18078810)
• male patients with mental retardation, short stature and hyperreflexia should be considered candidates for mutations in the JARID1C gene. (PMID:18697827)
• human NOT4 can polyubiquitinate human JARID1C/SMCX, a homolog of Jhd2, suggesting that this is likely a conserved mechanism (PMID:19346402)
• The two novel changes impair JARID1C protein function and are disease-causing mutations in the families reported. (PMID:19826449)
• identification of inactivating mutations in two genes–SETD2, a histone H3 lysine 36 methyltransferase, and JARID1C, a histone H3 lysine 4 demethylase–as well as mutations in the histone H3 lysine 27 demethylase, UTX in clear cell renal cell carcinoma (PMID:20054297)
• the JmjN domain of Jhd2 is important for its protein stability, and the plant homeodomain (PHD) finger mediates its chromatin association independent of H3K4 methylation (PMID:20538609)
• we describe clinical and genetic findings of a Brazilian family co-segregating a novel nonsense mutation (c.2172C>A) in exon 15 of KDM5C gene (PMID:21575681)
• Data show that von Hippel-Lindau (VHL) inactivation decreases H3K4Me3 levels through JARID1C, which alters gene expression and suppresses tumor growth. (PMID:21725364)
• Herein we present a large family with X Linked Intellectual Disability caused by a novel mutation c.2T > C in the start codon of the KDM5C gene (PMID:22326837)
• The KDM5C mutation carriers had higher mean scores on the abstract/visual and quantitative sections of the Stanford-Binet Intelligence Scale: Fourth Edition and lower mean short term memory scores. (PMID:22611640)
• We established that ARX polyA alterations damage the regulation of KDM5C expression. (PMID:23246292)
• DNA methylation at these three genes in blood correlated with dosage of KDM5C. (PMID:23356856)
• Mutation frequencies among CT images of clear cell RCCs were as follows: KDM5C, 6.9% (16 of 233). (PMID:24029645)
• Results indicate a KDM5C pathogenic mutational frequency of 0.7% among males with probable X-linked intellectual disability (XLID). (PMID:24583395)
• KDM5C is functionally involved in proliferation control of prostate cancer cells (PMID:25016185)
• These findings suggest that E2 recruits histone-modifying cellular proteins to the HPV LCR, resulting in transcriptional repression of E6 and E7. (PMID:25222147)
• Mutations in KDM5C gene in patients are described and their effect on gene expression, stability and catalytic activity is examined. Patient fibroblasts do not show global changes in histone methylation but several up-regulated genes were identified. (PMID:25666439)
• Data indicate the role for histone demethylase KDM5C/JARID1C in a specific phase of DNA replication in mammalian cells, through its demethylase activity on histone H3K4me3. (PMID:25712104)
• the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2, is reported. (PMID:26059843)
• BRMS1 expression in human breast cancer is negatively correlated with JARID1C expression. Our results, for the first time, portray a pivotal role of JARID1C in regulating metastatic behaviors of breast cancer cells (PMID:26182878)
• Expression of KDM5C in hepatocellular carcinoma tumor cells promoted cell migration and tumor invasion. (PMID:26503415)
• these data suggest that inactivation of JARID1C in renal cancer leads to heterochromatin disruption, genomic rearrangement, and aggressive ccRCCs. (PMID:26551685)
• study of non-synonymous mutations in the KDM5C ARID domain and evaluates effects of 2 syndromic Claes-Jensen-type disease-associated missense mutations (A77T and D87G) and 3 non-classified missense mutations (R108W, N142S, and R179H); analysis indicates, among the non-classified mutations, R108W is possibly a disease-associated mutation, and N142S and R179H are probably harmless (PMID:26580603)
• KDM5C is overexpressed in breast cancer cells and miR-138 regulates its expression. (PMID:26621457)
• Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. (PMID:26645689)
• The two mutations are present on the same maternal haplotype, suggesting that a postzygotic somatic mutation or a reversion error occurred at an early embryonic stage in the mother, leading to switched KDM5C mutations in the affected siblings. (PMID:26919706)
• Findings reveal a RACK7/KDM5C-regulated, dynamic interchange between histone H3K4me1 and H3K4me3 at active enhancers, representing an additional layer of regulation of enhancer activity. Authors propose that RACK7/KDM5C functions as an enhancer “brake” to ensure appropriate enhancer activity, which, when compromised, could contribute to tumorigenesis. (PMID:27058665)
• Results suggest that KDM5C mutations predispose to X-linked intellectual disability which accounts for 1-4% of cases in male patient. (PMID:27211531)
• The predicted structure of KDM5C was used to investigate the effects of disease-causing mutations, and it was shown that the mutations alter domain stability and inter-domain interactions. (PMID:27696497)
• Mutation in KDM5C gene is associated with cancer more frequently in males. (PMID:27869828)
• In vitro models indicated that KDM5C suppressed miR-320a transcription by directly binding to the promoter of miR-320a to prevent histone methylation. KITLG, an essential gene for ovarian development and primordial germ cell survival, was a direct target of miR-320a and that it was downregulated in 45,X fetal gonadal tissues. (PMID:27896428)
• SETD2 and KDM5C mutations were associated with prolonged overall survival in patients with metastatic clear cell renal cell carcinoma (PMID:28408295)
• HPV16 E6 protein interacts with histone demethylase KDM5C in ovarian cancer.HPV16 E6 protein destabilizes the KDM5C.KDM5C regulates cervical cancer cell EGFR and c-MET expression by modulating their super-enhancer H3K4 methylation dynamics. (PMID:29339538)
• In colon cancer cells, KDM5c might downregulate ABCC1 expression by demethylating the ABCC1 H3K4me3 in the TSS region, which can promote multidrug resistance (PMID:30257334)
• The BRD4-KDM5C-PTEN may be a new oncogenic pathway in CRPC development. (PMID:30921702)
• This article reviewed the most recent findings regarding cancer-specific metabolic reprogramming and the tumor-suppressive roles of IDH1/2, JARID1C/KDM5C and UTX/KDM6A. [review] (PMID:31221981)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm4c	ENSDARG00000061504
drosophila_melanogaster	Kdm5	FBGN0031759
caenorhabditis_elegans		WBGENE00004319

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM5A (ENSG00000073614), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 5C — P41229 (reviewed: P41229)

Alternative names: Histone demethylase JARID1C, Jumonji/ARID domain-containing protein 1C, Protein SmcX, Protein Xe169, [histone H3]-trimethyl-L-lysine(4) demethylase 5C

All UniProt accessions (10): P41229, A0A6M4C8G8, A0A8I5KPH7, A0A8I5KQR8, A0A8I5KTT1, A0A8I5KXH7, A0A8I5KYW1, A0A8I5QL21, F8WDK1, F8WF56

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 ‘Lys-9’, H3 ‘Lys-27’, H3 ‘Lys-36’, H3 ‘Lys-79’ or H4 ‘Lys-20’. Demethylates trimethylated and dimethylated but not monomethylated H3 ‘Lys-4’. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2.

Subunit / interactions. Part of two distinct complexes, one containing E2F6, and the other containing REST. Interacts with ZMYND8.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all tissues examined. Highest levels found in brain and skeletal muscle.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic, Claes-Jensen type (MRXSCJ) [MIM:300534] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSCJ patients manifest intellectual disability associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The inhibitor KDOAM-25 and others inhibit its demethylase activity, resulting to cell cycle arrest in myeloma cells.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Domain organisation. The first PHD-type zinc finger domain recognizes and binds H3-K9Me3. Both the JmjC domain and the JmjN domain are required for enzymatic activity.

Miscellaneous. Escapes X-inactivation.

Similarity. Belongs to the JARID1 histone demethylase family.

Isoforms (5)

UniProt ID	Names	Canonical?
P41229-1	1	yes
P41229-2	2
P41229-3	3
P41229-4	4
P41229-5	5

RefSeq proteins (8): NP_001140174, NP_001269551, NP_001340907, NP_001340908, NP_001340910, NP_001340911, NP_001340913, NP_004178* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR001965	Znf_PHD	Domain
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain
IPR004198	Znf_C5HC2	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013637	Lys_sp_deMease-like_dom	Domain
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR048615	KDM5_C-hel	Domain

Pfam: PF00628, PF01388, PF02373, PF02375, PF02928, PF08429, PF21323

Enzyme classification (BRENDA):

• EC 1.14.11.67 — [histone H3]-trimethyl-L-lysine4 demethylase (BRENDA: 13 organisms, 78 substrates, 122 inhibitors, 22 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[ACETYLATED HISTONE H3 21MER]-N6,N6,N6-TRIMETHYL	0.0168–0.0955	2
[ACETYLATED HISTONE H3 21MER]-N6,N6-DIMETHYL-L-L	0.0547–0.229	2
[HISTONE H3]-N6,N6-DIMETHYL-L-LYSINE4	0.0107–0.0128	2
[HISTONE H3 N-TERMINAL 13MER] N6,N6,N6-TRIMETHYL	0.489	1
[HISTONE H3 N-TERMINAL 18MER MUTANT K14A/R17A/K1	0.514	1
[HISTONE H3 N-TERMINAL 18MER MUTANT K14AC/K18AC]	0.249	1
[HISTONE H3 N-TERMINAL 18MER] N6,N6,N6-TRIMETHYL	0.0623	1
[HISTONE H3 N-TERMINAL 21MER MUTANT K9A] N6,N6,N	0.0219	1
[HISTONE H3 N-TERMINAL 21MER MUTANT Q5A] N6,N6,N	0.4152	1
[HISTONE H3 N-TERMINAL 21MER MUTANT R2A] N6,N6,N	0.1536	1
[HISTONE H3 N-TERMINAL 21MER MUTANT R8A] N6,N6,N	0.0551	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T3A] N6,N6,N	0.009	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T6A] N6,N6,N	0.0965	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T6S] N6,N6,N	0.0147	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T6V] N6,N6,N	0.0394	1

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 2-oxoglutarate + 3 O2 = L-lysyl(4)-[histone H3] + 3 formaldehyde + 3 succinate + 3 CO2 (RHEA:60208)

UniProt features (107 total): helix 28, strand 11, sequence variant 11, turn 8, compositionally biased region 7, binding site 7, modified residue 6, cross-link 6, splice variant 5, sequence conflict 5, region of interest 4, domain 3, zinc finger region 3, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5FWJ	X-RAY DIFFRACTION	2.1
2JRZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41229-F1	72.50	0.25

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 (7): 440; 514; 516; 522; 524; 532; 602

Post-translational modifications (12): 287, 301, 317, 893, 897, 1359, 205, 229, 244, 274, 295, 1127

Mutagenesis-validated functional residues (2):

Position	Phenotype
514–516	abolishes lysine-specific histone demethylase activity.
514	abolishes lysine-specific histone demethylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 368 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GGTGTGT_MIR329, TGCGCANK_UNKNOWN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MODULE_45, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MODULE_16, MODULE_308, NKX62_Q2, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, TGCTGAY_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, MODULE_123, TGANTCA_AP1_C, RYTTCCTG_ETS2_B

GO Biological Process (6): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892), rhythmic process (GO:0048511), chromatin organization (GO:0006325), methylation (GO:0032259)

GO Molecular Function (10): DNA binding (GO:0003677), zinc ion binding (GO:0008270), histone demethylase activity (GO:0032452), histone H3K4 demethylase activity (GO:0032453), histone H3K4me/H3K4me2/H3K4me3 demethylase activity (GO:0034647), protein binding (GO:0005515), methyltransferase activity (GO:0008168), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
biological_process	1
cellular component organization	1
metabolic process	1
nucleic acid binding	1
transition metal ion binding	1
protein demethylase activity	1
histone modifying activity	1
histone H3 demethylase activity	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H3K4 demethylase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

3926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM5C	EHMT2	Q96KQ7	985
KDM5C	HDAC1	Q13547	952
KDM5C	KDM6A	O15550	884
KDM5C	SETD2	Q9BYW2	857
KDM5C	HDAC2	Q92769	815
KDM5C	REST	Q13127	795
KDM5C	ZMYND8	Q9ULU4	790
KDM5C	PBRM1	Q86U86	772
KDM5C	UTY	O14607	753
KDM5C	IQSEC2	Q5JU85	749
KDM5C	UBA1	P22314	743
KDM5C	USP9X	Q93008	732
KDM5C	RCOR1	Q9UKL0	722
KDM5C	USP9Y	O00507	722
KDM5C	DDX3X	O00571	722

IntAct

82 interactions, top by confidence:

A	B	Type	Score
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
E2F6	KDM5C	psi-mi:“MI:0914”(association)	0.600
KDM5C	REST	psi-mi:“MI:0915”(physical association)	0.560
IER2	KPNA3	psi-mi:“MI:0914”(association)	0.530
SKP2	DPYSL4	psi-mi:“MI:0914”(association)	0.530
TRIM35	MTA2	psi-mi:“MI:0914”(association)	0.530
KDM5C	TRIM28	psi-mi:“MI:0914”(association)	0.530
SNAPC4	KDM5C	psi-mi:“MI:0914”(association)	0.530
E2	KDM5C	psi-mi:“MI:0915”(physical association)	0.500
E2	BRD4	psi-mi:“MI:0914”(association)	0.500
KDM5C		psi-mi:“MI:0871”(demethylation reaction)	0.440
PEX14	KDM5C	psi-mi:“MI:0407”(direct interaction)	0.440
KDM5C	CSNK2A1	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
KDM5C	NCOR1	psi-mi:“MI:0914”(association)	0.350
REST	NCOR1	psi-mi:“MI:0914”(association)	0.350
KDM5C	UBB	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
TXNIP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
KRT2	IFT56	psi-mi:“MI:0914”(association)	0.350
ARHGAP25	UBA6	psi-mi:“MI:0914”(association)	0.350
FBXO10	BLTP3B	psi-mi:“MI:0914”(association)	0.350
IQCN	TARS3	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350

BioGRID (175): KDM5C (Affinity Capture-RNA), KDM5C (Affinity Capture-MS), KDM5C (Affinity Capture-MS), KDM5C (Affinity Capture-MS), KDM5C (Affinity Capture-MS), KDM5C (Affinity Capture-MS), KDM5C (Co-fractionation), LSM2 (Co-fractionation), PITHD1 (Co-fractionation), CSNK2A1 (Affinity Capture-MS), CSNK2B (Affinity Capture-MS), E2F6 (Affinity Capture-MS), MAX (Affinity Capture-MS), SET (Affinity Capture-MS), XPO1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P5, A1L1R0, A8E7C5, A8PJX4, A9UZS7, B3MG50, B3N9E4, B4GDK5, B4HR78, B4KSY3, B4P238, E7EXT2, E7F187, F7AEX0, O43076, O80452, O88379, P0CU29, P40486, P41229, P41230, P69735, P83093, P91133, Q05B18, Q09305, Q0E9G3, Q12874, Q14738, Q17N71, Q292G3, Q2PE14, Q38JA7, Q58CP9, Q7PTC5, Q7Q9F6, Q7Z3E5, Q80Y84, Q851S7, Q8R2R3

Diamond homologs: A0A1W2PPD8, A1A5Q5, A1YVX4, B2RXH2, C0SUT9, F4I240, F4I6G4, F4KIX0, O64752, O75164, O94953, P29375, P39956, P41229, P41230, P47156, Q03833, Q10RP4, Q1LVC2, Q23541, Q30DN6, Q336N8, Q38JA7, Q3U2K5, Q3UXZ9, Q53WJ1, Q5F3R2, Q5N712, Q5RD88, Q5XUN4, Q61T02, Q62240, Q62315, Q6B0I6, Q6BDA0, Q6IQX0, Q80Y84, Q8BW72, Q8GUI6, Q8VCD7

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
KDM5C	“up-regulates activity”	H3C1	demethylation
KDM5C	“up-regulates activity”	H3-4	demethylation
BRD4	“up-regulates quantity by expression”	KDM5C	“transcriptional regulation”
KDM5C	“down-regulates quantity by repression”	PTEN	“transcriptional regulation”
KDM5C	“up-regulates activity”	“Histone H3”	demethylation
CNOT4	“down-regulates quantity by destabilization”	KDM5C	ubiquitination
HIF1A	“up-regulates quantity by expression”	KDM5C	“transcriptional regulation”
RNF4	“up-regulates activity”	KDM5C	sumoylation
EPAS1	“up-regulates quantity by expression”	KDM5C	“transcriptional regulation”
KDM5C	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
KDM5C	“down-regulates quantity by repression”	SYN1	“transcriptional regulation”
KDM5C	“down-regulates quantity by repression”	BDNF	“transcriptional regulation”
2-oxoglutarate(2-)	“up-regulates activity”	KDM5C	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	11	5.8×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 7 cancer types — CCRCC, HNSC, LUAD, OVT, PAAD, PCM, RCC.

Clinical variants and AI predictions

ClinVar

1197 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	102
Likely pathogenic	83
Uncertain significance	414
Likely benign	271
Benign	82

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034062	NM_004187.5(KDM5C):c.3244dup (p.Arg1082fs)	Pathogenic
1174937	NM_004187.5(KDM5C):c.80C>T (p.Pro27Leu)	Pathogenic
1185761	NM_004187.5(KDM5C):c.1013dup (p.Leu339fs)	Pathogenic
1191492	NM_004187.5(KDM5C):c.2851C>T (p.Arg951Ter)	Pathogenic
1209852	NM_004187.5(KDM5C):c.2116C>T (p.Gln706Ter)	Pathogenic
1319929	NM_004187.5(KDM5C):c.1361_1362del (p.Pro454fs)	Pathogenic
1334775	NM_004187.5(KDM5C):c.2517_2622del	Pathogenic
1342084	NM_004187.5(KDM5C):c.2779C>T (p.Gln927Ter)	Pathogenic
1361205	NM_004187.5(KDM5C):c.807dup (p.Thr270fs)	Pathogenic
1362416	NM_004187.5(KDM5C):c.2064del (p.Ile689fs)	Pathogenic
1381696	NM_004187.5(KDM5C):c.1766del (p.Cys589fs)	Pathogenic
1452263	NM_004187.5(KDM5C):c.3170del (p.Val1057fs)	Pathogenic
1455486	NM_004187.5(KDM5C):c.2908C>T (p.Gln970Ter)	Pathogenic
1455857	NM_004187.5(KDM5C):c.1180_1181del (p.Leu394fs)	Pathogenic
155698	GRCh38/hg38 Xp11.22(chrX:51707794-53229764)x0	Pathogenic
1679365	NM_004187.5(KDM5C):c.12dup (p.Ser5fs)	Pathogenic
1684146	NM_004187.5(KDM5C):c.2427_2430del (p.Glu810fs)	Pathogenic
1685904	NM_004187.5(KDM5C):c.997G>C (p.Gly333Arg)	Pathogenic
1685906	NM_004187.5(KDM5C):c.994C>T (p.Arg332Ter)	Pathogenic
1703597	GRCh37/hg19 Xp11.22(chrX:53104986-54034505)	Pathogenic
1710735	NM_004187.5(KDM5C):c.202C>T (p.Arg68Ter)	Pathogenic
1735378	NM_004187.5(KDM5C):c.3835C>T (p.Gln1279Ter)	Pathogenic
1773537	NM_004187.5(KDM5C):c.147del (p.Ala50fs)	Pathogenic
1803987	NM_004187.5(KDM5C):c.2214C>A (p.Cys738Ter)	Pathogenic
1805730	NM_004187.5(KDM5C):c.2813_2816dup (p.Pro940fs)	Pathogenic
195601	NM_004187.5(KDM5C):c.3126_3128delinsCAGG (p.Asp1043fs)	Pathogenic
196375	NM_004187.5(KDM5C):c.351+1G>T	Pathogenic
197228	NM_004187.5(KDM5C):c.486T>A (p.Tyr162Ter)	Pathogenic
1992549	NM_004187.5(KDM5C):c.1762C>T (p.Gln588Ter)	Pathogenic
2045699	NM_004187.5(KDM5C):c.3409_3410delinsT (p.Ala1137fs)	Pathogenic

SpliceAI

3800 predictions. Top by Δscore:

Variant	Effect	Δscore
X:53193431:CCTCA:C	donor_loss	1.0000
X:53193432:CTCA:C	donor_loss	1.0000
X:53193433:TCACC:T	donor_loss	1.0000
X:53193434:CACCT:C	donor_loss	1.0000
X:53193435:A:AC	donor_gain	1.0000
X:53193435:ACCT:A	donor_gain	1.0000
X:53193436:C:CC	donor_gain	1.0000
X:53193436:C:CT	donor_loss	1.0000
X:53193436:CCT:C	donor_gain	1.0000
X:53193436:CCTC:C	donor_gain	1.0000
X:53193438:T:TA	donor_gain	1.0000
X:53193632:CAGAT:C	acceptor_gain	1.0000
X:53193633:AGAT:A	acceptor_gain	1.0000
X:53193634:GAT:G	acceptor_gain	1.0000
X:53193634:GATCT:G	acceptor_loss	1.0000
X:53193635:AT:A	acceptor_gain	1.0000
X:53193635:ATCT:A	acceptor_loss	1.0000
X:53193636:TCTA:T	acceptor_loss	1.0000
X:53193637:C:CC	acceptor_gain	1.0000
X:53193644:G:C	acceptor_gain	1.0000
X:53193644:G:GC	acceptor_gain	1.0000
X:53193645:T:C	acceptor_gain	1.0000
X:53193645:T:TC	acceptor_gain	1.0000
X:53193648:C:CT	acceptor_gain	1.0000
X:53193649:A:T	acceptor_gain	1.0000
X:53193776:TCTTA:T	donor_loss	1.0000
X:53193778:TTACC:T	donor_loss	1.0000
X:53193779:TACCT:T	donor_loss	1.0000
X:53193780:A:AT	donor_loss	1.0000
X:53193781:CCT:C	donor_loss	1.0000

AlphaMissense

10118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:53194344:A:G	L1278P	1.000
X:53195264:G:C	F1089L	1.000
X:53195264:G:T	F1089L	1.000
X:53195265:A:G	F1089S	1.000
X:53195266:A:G	F1089L	1.000
X:53195290:A:G	W1081R	1.000
X:53195290:A:T	W1081R	1.000
X:53195942:A:G	W1032R	1.000
X:53195942:A:T	W1032R	1.000
X:53198813:C:A	W773C	1.000
X:53198813:C:G	W773C	1.000
X:53198815:A:G	W773R	1.000
X:53198815:A:T	W773R	1.000
X:53198853:A:G	L760P	1.000
X:53198865:A:G	L756P	1.000
X:53198881:A:C	Y751D	1.000
X:53198883:C:G	R750P	1.000
X:53198887:A:C	Y749D	1.000
X:53198887:A:G	Y749H	1.000
X:53198887:A:T	Y749N	1.000
X:53198980:A:G	L747P	1.000
X:53199030:G:C	C730W	1.000
X:53199031:C:G	C730S	1.000
X:53199031:C:T	C730Y	1.000
X:53199032:A:G	C730R	1.000
X:53199032:A:T	C730S	1.000
X:53199057:G:C	C721W	1.000
X:53199058:C:T	C721Y	1.000
X:53199059:A:G	C721R	1.000
X:53199067:G:T	A718D	1.000

dbSNP variants (sampled 300 via entrez): RS1000108942 (X:53222472 C>T), RS1000912288 (X:53190992 C>A), RS1001026454 (X:53190761 C>T), RS1001142994 (X:53201259 A>C), RS1001186364 (X:53182524 C>T), RS1001339648 (X:53176640 A>C,G), RS1001392021 (X:53177003 C>G,T), RS1001492708 (X:53200822 T>C), RS1001588893 (X:53195691 C>A), RS1001817214 (X:53205477 C>T), RS1001858962 (X:53186890 A>C), RS1002097153 (X:53202975 C>A,T), RS1002164776 (X:53204879 A>G), RS1002173704 (X:53213334 T>C), RS1002288281 (X:53213609 A>C,T)

Disease associations

OMIM: gene MIM:314690 | disease phenotypes: MIM:300534, MIM:309510, MIM:300705, MIM:147920, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic X-linked intellectual disability Claes-Jensen type	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked syndromic intellectual disability	Definitive	XL

Mondo (7): syndromic X-linked intellectual disability Claes-Jensen type (MONDO:0010355), X-linked syndromic intellectual disability (MONDO:0020119), neurodevelopmental disorder (MONDO:0700092), chromosome Xp11.22 duplication syndrome (MONDO:0010406), intellectual disability (MONDO:0001071), Kabuki syndrome (MONDO:0016512), plasma cell myeloma (MONDO:0009693)

Orphanet (8): KDM5C-related syndromic X-linked intellectual disability (Orphanet:85279), X-linked non-syndromic intellectual disability (Orphanet:777), Kabuki syndrome (Orphanet:2322), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), Rare genetic intellectual disability (Orphanet:183757), OBSOLETE: X-linked syndromic intellectual disability (Orphanet:98464), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000221	Furrowed tongue
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000297	Facial hypotonia
HP:0000303	Mandibular prognathia
HP:0000319	Smooth philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000350	Small forehead
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000699	Diastema
HP:0000711	Restlessness
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000744	Low frustration tolerance
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000767	Pectus excavatum

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002394_216	Monocyte percentage of white cells	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D065886	Neurodevelopmental Disorders	F03.625
C537705	Kabuki syndrome (supp.)
C564494	Mental Retardation, X-Linked, Syndromic, Jarid1c-Related (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2163176 (SINGLE PROTEIN), CHEMBL6066033 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 7,561 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL70927	DEFERIPRONE	4	7,561

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.14.11.- Histone demethylases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
IOX2	Inhibition	6.8	pIC50
GSK-J1	Inhibition	6.26	pIC50
PBIT	Inhibition	5.31	pIC50
GSK-J4	Inhibition	4.82	pIC50

Binding affinities (BindingDB)

3 measured of 26 human assays (26 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4’-(phenethylcarbamoyl)-[2,2’-bipyridine]-4-carboxylic acid (N3)	IC50	61 nM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
3-((1-methyl-1Hpyrrolo[2,3-b]pyridin-3-yl)amino)isonicotinic acid (N12)	IC50	550 nM	US-10336727: Histone demethylase inhibitors

ChEMBL bioactivities

170 potent at pChembl≥5 of 192 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.23	IC50	5.84	nM	CHEMBL4536443
8.21	IC50	6.24	nM	CHEMBL4542928
8.06	IC50	8.8	nM	CHEMBL5199483
8.00	IC50	9.92	nM	CHEMBL3787669
7.92	IC50	12	nM	CHEMBL3774692
7.87	IC50	13.6	nM	CHEMBL5569973
7.85	IC50	14	nM	CHEMBL4438830
7.85	IC50	14	nM	CHEMBL4454253
7.68	IC50	21	nM	CHEMBL3775040
7.68	IC50	21	nM	CHEMBL3775451
7.66	IC50	22	nM	CHEMBL3775516
7.64	IC50	23	nM	CHEMBL3775899
7.64	IC50	23	nM	CHEMBL3774940
7.62	IC50	24	nM	CHEMBL3775814
7.61	IC50	24.8	nM	CHEMBL4782583
7.60	IC50	25	nM	CHEMBL5287732
7.57	IC50	27	nM	CHEMBL4078388
7.52	IC50	30	nM	CHEMBL3108956
7.52	IC50	30	nM	CHEMBL3775362
7.52	IC50	30	nM	CHEMBL4592908
7.50	IC50	32	nM	CHEMBL3774665
7.47	IC50	34	nM	CHEMBL3775545
7.46	IC50	35	nM	CHEMBL4440395
7.42	IC50	38	nM	CHEMBL4516101
7.39	IC50	41	nM	CHEMBL3774392
7.39	IC50	41	nM	CHEMBL3775465
7.34	IC50	46	nM	CHEMBL3775668
7.32	IC50	48	nM	CHEMBL4585876
7.30	IC50	50	nM	CHEMBL3775956
7.30	IC50	50	nM	CHEMBL3775277
7.29	IC50	51	nM	CHEMBL3775894
7.28	IC50	52	nM	CHEMBL3775953
7.28	IC50	53	nM	CHEMBL4466130
7.27	IC50	54	nM	CHEMBL3775121
7.27	IC50	54	nM	CHEMBL4558689
7.26	IC50	55	nM	CHEMBL4088737
7.24	IC50	57	nM	CHEMBL3775130
7.23	IC50	59	nM	CHEMBL4567766
7.23	IC50	59	nM	CHEMBL3787669
7.22	IC50	60	nM	CHEMBL3775095
7.20	IC50	63.1	nM	CHEMBL3771180
7.20	IC50	63	nM	CHEMBL4520178
7.19	IC50	64	nM	CHEMBL3774922
7.19	IC50	65	nM	CHEMBL3774537
7.19	IC50	65	nM	CHEMBL4088737
7.18	IC50	65.5	nM	CHEMBL3785583
7.17	IC50	67	nM	CHEMBL3775977
7.16	IC50	70	nM	CHEMBL3775548
7.16	IC50	69	nM	CHEMBL4078388
7.12	IC50	76	nM	CHEMBL3775135

PubChem BioAssay actives

204 with measured affinity, of 281 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
5-[4-[[hexyl(methyl)amino]methyl]phenyl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1624962: Inhibition of full-length human N-terminal FLAG/His-tagged KDM5C (2 to 1560 residues) expressed in baculovirus infected Sf9 insect cells using H3(1-21)K4(Me3)-GGK(Biotin)/2-OG as substrate measured after 1 hr by Alphalisa assay	ic50	0.0058	uM
5-[4-[2-[hexyl(methyl)amino]ethyl]phenyl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1624962: Inhibition of full-length human N-terminal FLAG/His-tagged KDM5C (2 to 1560 residues) expressed in baculovirus infected Sf9 insect cells using H3(1-21)K4(Me3)-GGK(Biotin)/2-OG as substrate measured after 1 hr by Alphalisa assay	ic50	0.0062	uM
2-[1-[2-[hexyl(methyl)amino]ethyl]triazol-4-yl]pyridine-4-carboxylic acid	1872462: Inhibition of N-terminal FLAG/His-tagged full-length human KDM5C (2 to 1560 residues) expressed in baculovirus infected Sf9 insect cells using peptide substrate incubated for 2 hrs by Alpha Screen assay	ic50	0.0088	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	2106950: Inhibition of KDM5C (unknown origin) incubated for 2 hrs by Alphascreen assay	ic50	0.0099	uM
2-(2-amino-1,3-thiazol-4-yl)pyridine-4-carboxylic acid	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0120	uM
2-[[[2-[2-[butyl(methyl)amino]ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	2106950: Inhibition of KDM5C (unknown origin) incubated for 2 hrs by Alphascreen assay	ic50	0.0136	uM
8-[4-[2-[4-[3-[2-(dimethylamino)ethyl]phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0140	uM
7-oxo-5-phenyl-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627990: Inhibition of KDM5C (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/2-OG as substrate/co-factor by TR-FRET assay	ic50	0.0140	uM
8-[4-[2-[4-(1,3-benzodioxol-5-ylmethyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0210	uM
8-[4-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0210	uM
8-[4-[2-[4-[[4-(trifluoromethyl)phenyl]methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0220	uM
8-[4-[2-[4-[(4-chlorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0230	uM
8-[4-[2-[4-[(3,4-dichlorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0230	uM
4-[1-[2-[1-(4-oxo-3H-pyrido[3,4-d]pyrimidin-8-yl)pyrazol-4-yl]ethyl]piperidin-4-yl]benzonitrile	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0240	uM
1-(4-methoxyphenyl)-N-(2-methyl-2-morpholin-4-ylpropyl)-3-phenylpyrazole-4-carboxamide	1690875: Inhibition of KDM5C (unknown origin)	ic50	0.0248	uM
[(3R)-3-[6-methyl-4-(1-methylpyrazol-4-yl)-2-pyridinyl]pyrrolidin-1-yl]-(5-propan-2-yl-1H-pyrazol-3-yl)methanone	1934024: Inhibition of KDM5C (unknown origin ) by Alphascreen assay	ic50	0.0250	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxamide	1885333: Inhibition of KDM5C (unknown origin) in presence of 4 uM 2-OG	ic50	0.0270	uM
lithium 2-[(furan-2-ylmethylamino)methyl]pyridine-4-carboxylate	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0300	uM
8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0300	uM
2-(4-methoxycarbonyl-2-pyridinyl)pyridine-4-carboxylic acid	1066182: Inhibition of recombinant JARID1C (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	0.0300	uM
8-[4-[2-[4-(4-methylsulfonylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0320	uM
8-[4-[2-[4-(4-methoxyphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0340	uM
8-[4-[2-[4-[3-(2-morpholin-4-ylethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0350	uM
8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0380	uM
8-[4-[2-(4-benzylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0410	uM
8-[4-[2-[4-[(3-methoxyphenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0410	uM
8-[4-[2-(4-thiophen-2-ylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0460	uM
8-[4-[2-[4-[4-[2-(dimethylamino)ethyl]phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0480	uM
8-[4-[2-[4-(pyridin-3-ylmethyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0500	uM
8-[4-[2-(4-pyridin-4-ylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0500	uM
8-[4-[2-[4-(3,5-dichlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0510	uM
8-[4-[2-[4-(4-fluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0520	uM
8-[4-[2-[4-[4-(2-morpholin-4-ylethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0530	uM
8-[4-[2-[4-(2,4-difluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0540	uM
8-[4-[2-[4-(3-pyrimidin-5-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0540	uM
N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide	1453522: Inhibition of recombinant human N-terminal FLAG-tagged KDM5C expressed in baculovirus infected Sf9 insect cells using H3K4me3 peptide as substrate after 30 to 45 mins by TR-FRET assay	ic50	0.0550	uM
8-[4-[2-[4-[(5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0570	uM
8-[4-[2-[4-(3-pyridin-3-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0590	uM
lithium 2-[(benzylamino)methyl]pyridine-4-carboxylate	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0600	uM
8-[4-[2-[4-(3-tert-butylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0630	uM
2-(1-benzylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281025: Inhibition of KDM5C catalytic domain (1 -764 aa) (unknown origin) expressed in Sf9 cells using H3K4Me3 peptide as substrate by RFMS assay	ic50	0.0631	uM
4-[[methyl-[3-[1-(4-oxo-3H-pyrido[3,4-d]pyrimidin-8-yl)pyrazol-4-yl]propyl]amino]methyl]benzonitrile	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0640	uM
2-(1-benzylpyrazol-4-yl)oxy-2,3,4a,5,6,7,8,8a-octahydro-1H-pyrido[3,4-d]pyrimidin-4-one	1801992: Demethylase AlphaScreen Assay from Article 10.1038/nchembio.2087: “Structural analysis of human KDM5B guides histone demethylase inhibitor development.”	ic50	0.0650	uM
8-[4-[2-[4-(3-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0650	uM
5-(1-tert-butylpyrazol-4-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627221: Inhibition of KDM5C (unknown origin)	ic50	0.0655	uM
8-[4-[2-[4-(4-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0670	uM
8-[4-[2-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0700	uM
4-[[methyl-[2-[1-(4-oxo-3H-pyrido[3,4-d]pyrimidin-8-yl)pyrazol-4-yl]ethyl]amino]methyl]benzonitrile	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0760	uM
8-[4-[2-[(4-fluorophenyl)methyl-methylamino]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282545: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay	ic50	0.0780	uM
8-[4-[2-[4-(3-pyridin-2-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556104: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay	ic50	0.0790	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
FR900359	decreases phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
fumonisin B1	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, decreases methylation	1
Bortezomib	decreases expression	1
Decitabine	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	decreases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

ChEMBL screening assays

49 unique, capped per target: 49 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2167518	Binding	Inhibition of human KDM5C catalytic domain expressed in Sf9 cells using methyl lysine peptide substrate by AlphaScreen assay	Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases. — J Med Chem

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2ZM	Abcam HEK293T KDM5C KO 1	Transformed cell line	Female
CVCL_B2ZN	Abcam HEK293T KDM5C KO 2	Transformed cell line	Female
CVCL_C6MY	USZ22-EMC2	Cancer cell line	Male
CVCL_SU45	HAP1 KDM5C (-) 1	Cancer cell line	Male
CVCL_SU46	HAP1 KDM5C (-) 2	Cancer cell line	Male
CVCL_SU47	HAP1 KDM5C (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays