Kabuki syndrome 1

Summary

Kabuki syndrome 1 (MONDO:0007843) is a disease caused by KMT2D (GenCC Definitive), with 12 cohort genes and 1 clinical trial. The dominant Reactome pathway is Formation of WDR5-containing histone-modifying complexes (5 cohort genes).

At a glance

• Causal gene: KMT2D (GenCC Definitive)
• Cohort genes: 12
• ClinVar variants: 1,498
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Kabuki syndrome 1
Mondo ID	MONDO:0007843
OMIM	147920
GARD	0024579
Is cancer (heuristic)	no

Also known as: KABUK1 · Kabuki syndrome 1 · Kabuki syndrome type 1

Data availability: 1,498 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Kabuki syndrome › Kabuki syndrome 1

Related subtypes (1): Kabuki syndrome 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

231 conflicting classifications of pathogenicity, 141 uncertain significance, 125 pathogenic, 37 likely pathogenic, 29 benign/likely benign, 19 likely benign, 14 pathogenic/likely pathogenic, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012175	NM_003482.4(KMT2D):c.14826dup (p.Glu4943Ter)	KMT2D	Pathogenic	criteria provided, single submitter
1012322	NM_003482.4(KMT2D):c.4464del (p.Cys1489fs)	KMT2D	Pathogenic	criteria provided, single submitter
1027388	NM_003482.4(KMT2D):c.5642_5644+1del	KMT2D	Pathogenic	no assertion criteria provided
1027396	NM_003482.4(KMT2D):c.11320C>T (p.Gln3774Ter)	KMT2D	Pathogenic	no assertion criteria provided
1027399	NM_003482.4(KMT2D):c.5468-1G>A	KMT2D	Pathogenic	no assertion criteria provided
1028116	NM_003482.4(KMT2D):c.6110-2A>G	KMT2D	Pathogenic	criteria provided, single submitter
1030668	NM_003482.4(KMT2D):c.10688dup (p.Leu3564fs)	KMT2D	Pathogenic	criteria provided, single submitter
1033587	NM_003482.4(KMT2D):c.204_205del (p.Leu68_Cys69insTer)	KMT2D	Pathogenic	criteria provided, single submitter
1033591	NM_003482.4(KMT2D):c.7378del (p.Arg2460fs)	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1033593	NM_003482.4(KMT2D):c.7938del (p.Asp2647fs)	KMT2D	Pathogenic	criteria provided, single submitter
1065457	NM_003482.4(KMT2D):c.9773del (p.Lys3258fs)	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1065471	NM_003482.4(KMT2D):c.1491_1492del (p.Pro497_Pro498insTer)	KMT2D	Pathogenic	criteria provided, single submitter
1069469	NM_003482.4(KMT2D):c.2173_2174del (p.Leu725fs)	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1164061	NM_003482.4(KMT2D):c.7650del (p.Val2551fs)	KMT2D	Pathogenic	no assertion criteria provided
1172600	NM_003482.4(KMT2D):c.16469_16470del (p.Lys5490fs)	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1175186	NM_003482.4(KMT2D):c.14113_14123del (p.Ile4705fs)	KMT2D	Pathogenic	criteria provided, single submitter
1184993	NM_003482.4(KMT2D):c.11461C>T (p.Gln3821Ter)	KMT2D	Pathogenic	criteria provided, single submitter
1299667	NM_003482.4(KMT2D):c.14923del (p.Arg4975fs)	KMT2D	Pathogenic	no assertion criteria provided
1301886	NM_003482.4(KMT2D):c.16522-5_16522-2del	KMT2D	Pathogenic	criteria provided, single submitter
1302009	NM_003482.4(KMT2D):c.10295dup (p.Leu3432fs)	KMT2D	Pathogenic	criteria provided, single submitter
1320100	NM_003482.4(KMT2D):c.7407_7408insT (p.Pro2470fs)	KMT2D	Pathogenic	criteria provided, single submitter
1320116	NM_003482.4(KMT2D):c.15104G>A (p.Cys5035Tyr)	KMT2D	Pathogenic	criteria provided, single submitter
1320118	NM_003482.4(KMT2D):c.10109del (p.Gln3370fs)	KMT2D	Pathogenic	criteria provided, single submitter
1320193	NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs)	KMT2D	Pathogenic	criteria provided, single submitter
1333189	NM_003482.4(KMT2D):c.4379dup (p.Leu1461fs)	KMT2D	Pathogenic/Likely pathogenic	no assertion criteria provided
1333630	NM_003482.4(KMT2D):c.11731C>T (p.Gln3911Ter)	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1333901	NM_003482.4(KMT2D):c.2488G>T (p.Glu830Ter)	KMT2D	Pathogenic	criteria provided, single submitter
1343223	NM_003482.4(KMT2D):c.9872_9882dup (p.Met3295fs)	KMT2D	Pathogenic	criteria provided, single submitter
1458717	NM_003482.4(KMT2D):c.10740+1G>A	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1496460	NM_003482.4(KMT2D):c.5189-1G>C	KMT2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 31 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
KMT2D	Definitive	Autosomal dominant	Kabuki syndrome 1	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KMT2D	Orphanet:2322	Kabuki syndrome
KMT2D	Orphanet:589856	Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
KDM6A	Orphanet:2322	Kabuki syndrome
KMT2B	Orphanet:528084	Non-specific syndromic intellectual disability
KMT2B	Orphanet:589618	Dystonia 28
ALG1	Orphanet:79327	ALG1-CDG
ZBTB24	Orphanet:2268	ICF syndrome
KIDINS220	Orphanet:521390	Spastic paraplegia-intellectual disability-nystagmus-obesity syndrome
DNMT3B	Orphanet:2268	ICF syndrome
DNMT3B	Orphanet:269	Facioscapulohumeral dystrophy
HCFC1	Orphanet:369962	Methylmalonic acidemia with homocystinuria, type cblX
HCFC1	Orphanet:777	X-linked non-syndromic intellectual disability
KMT2A	Orphanet:319182	Wiedemann-Steiner syndrome
KMT2A	Orphanet:402017	Acute myeloid leukemia with t(9;11)(p22;q23)
KMT2A	Orphanet:585918	B-lymphoblastic leukemia/lymphoma with t(v;11q23.3)
KMT2A	Orphanet:589534	Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2)
KMT2A	Orphanet:589595	Mixed phenotype acute leukemia with t(v;11q23.3)
KMT2A	Orphanet:98831	Acute myeloid leukemia with 11q23 abnormalities
KMT2A	Orphanet:98835	Acute undifferentiated leukemia

Cohort genes → proteins

12 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	gencc,clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
KDM6A	HGNC:12637	ENSG00000147050	O15550	Lysine-specific demethylase 6A	clinvar
KMT2B	HGNC:15840	ENSG00000272333	Q9UMN6	Histone-lysine N-methyltransferase 2B	clinvar
CCNT1	HGNC:1599	ENSG00000129315	O60563	Cyclin-T1	clinvar
ALG1	HGNC:18294	ENSG00000033011	Q9BT22	Chitobiosyldiphosphodolichol beta-mannosyltransferase	clinvar
ZBTB24	HGNC:21143	ENSG00000112365	O43167	Zinc finger and BTB domain-containing protein 24	clinvar
KIDINS220	HGNC:29508	ENSG00000134313	Q9ULH0	Kinase D-interacting substrate of 220 kDa	clinvar
DNMT3B	HGNC:2979	ENSG00000088305	Q9UBC3	DNA (cytosine-5)-methyltransferase 3B	clinvar
ATP5MF-PTCD1	HGNC:38844	ENSG00000248919		ATP5MF-PTCD1 readthrough	clinvar
HCFC1	HGNC:4839	ENSG00000172534	P51610	Host cell factor 1	clinvar
KMT2A	HGNC:7132	ENSG00000118058	Q03164	Histone-lysine N-methyltransferase 2A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
KDM6A	Lysine-specific demethylase 6A	Histone demethylase that specifically demethylates ‘Lys-27’ of histone H3, thereby playing a central role in histone code.
KMT2B	Histone-lysine N-methyltransferase 2B	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism.
CCNT1	Cyclin-T1	Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating th…
ALG1	Chitobiosyldiphosphodolichol beta-mannosyltransferase	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
ZBTB24	Zinc finger and BTB domain-containing protein 24	May be involved in BMP2-induced transcription.
KIDINS220	Kinase D-interacting substrate of 220 kDa	Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism.
DNMT3B	DNA (cytosine-5)-methyltransferase 3B	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
HCFC1	Host cell factor 1	Transcriptional coregulator.
KMT2A	Histone-lysine N-methyltransferase 2A	Histone methyltransferase that plays an essential role in early development and hematopoiesis.

Protein-family classification

Druggable: 3 · Difficult: 6 · Unknown: 3 · Druggable fraction: 0.25

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	5	3.4×	0.049
Antibody/Immunoglobulin	1	2.4×	0.570
Enzyme (other)	2	2.0×	0.570
Scaffold/PPI	1	1.4×	0.639
Other/Unknown	3	0.5×	0.993

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
KDM6A	Enzyme (other)	yes	1.14.11.68	JmjC_dom, TPR-like_helical_dom_sf, TPR_rpt
KMT2B	Transcription factor	no		SET_dom, Znf_PHD, Znf_CXXC
CCNT1	Other/Unknown	no		Cyclin_N, Cyclin-like_dom, Cyclin-like_sf
ALG1	Enzyme (other)	yes	2.4.1.142	Glyco_trans_1, ALG1-like
ZBTB24	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
KIDINS220	Scaffold/PPI	no		Ankyrin_rpt, KAP_P-loop, SAM/pointed_sf
DNMT3B	Transcription factor	no	2.1.1.37	PWWP_dom, C5_MeTfrase, Znf_FYVE_PHD
ATP5MF-PTCD1	Other/Unknown	no
HCFC1	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, Kelch-typ_b-propeller
KMT2A	Transcription factor	no		SET_dom, Bromodomain, Znf_PHD

Expression context

Cohort genes with no expression data: 0.

9 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	3
buccal mucosa cell	2
sural nerve	2
male germ line stem cell (sensu Vertebrata) in testis	2
ventricular zone	2
oocyte	2
tendon of biceps brachii	2
medial globus pallidus	1
bone marrow cell	1
left testis	1
lower esophagus mucosa	1
right testis	1
renal medulla	1
sperm	1
superior surface of tongue	1
body of pancreas	1
stromal cell of endometrium	1
Brodmann (1909) area 23	1
endothelial cell	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
KDM6A	286	ubiquitous	yes	secondary oocyte, oocyte, bone marrow cell
KMT2B	269	ubiquitous	marker	right testis, left testis, lower esophagus mucosa
CCNT1	274	ubiquitous	marker	sperm, superior surface of tongue, renal medulla
ALG1	185	ubiquitous	marker	stromal cell of endometrium, buccal mucosa cell, body of pancreas
ZBTB24	256	ubiquitous	yes	endothelial cell, Brodmann (1909) area 23, tendon of biceps brachii
KIDINS220	299	ubiquitous	marker	middle frontal gyrus, cortical plate, paraflocculus
DNMT3B	184	ubiquitous	marker	secondary oocyte, oocyte, hair follicle
ATP5MF-PTCD1	131	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, gastrocnemius
HCFC1	274	ubiquitous	marker	tendon of biceps brachii, parotid gland, skeletal muscle tissue of rectus abdominis
KMT2A	285	ubiquitous	marker	ventricular zone, colonic epithelium, sural nerve

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KDM6A	8,825
BRCA2	4,839
DNMT3B	4,378
KMT2A	4,314
CCNT1	3,235
KMT2D	3,223
KMT2B	2,639
HCFC1	2,637
ALG1	2,187
KIDINS220	2,084

Intra-cohort edges

A	B	Sources
DNMT3B	ZBTB24	string_interaction
HCFC1	KMT2A	biogrid_interaction, intact
KDM6A	KMT2D	intact, string_interaction
KMT2A	KMT2B	intact, string_interaction
KMT2A	KMT2D	string_interaction
KMT2B	KMT2D	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KMT2A	Q03164	60
DNMT3B	Q9UBC3	47
CCNT1	O60563	29
BRCA2	P51587	14
KMT2D	O14686	11
HCFC1	P51610	11
KDM6A	O15550	5
KMT2B	Q9UMN6	4
KIDINS220	Q9ULH0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG1	Q9BT22	93.24
ZBTB24	O43167	56.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 116. Enrichment computed across 12 evidence-associated genes (10 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of WDR5-containing histone-modifying complexes	5	132.8×	2e-08	KMT2D, KDM6A, KMT2B, HCFC1, KMT2A
Epigenetic regulation by WDR5-containing histone modifying complexes	4	61.7×	2e-05	KMT2D, KDM6A, KMT2B, KMT2A
Chromatin organization	4	32.6×	2e-04	KMT2D, KDM6A, KMT2B, KMT2A
Chromatin modifying enzymes	4	28.9×	2e-04	KMT2D, KDM6A, KMT2B, KMT2A
Epigenetic regulation of gene expression	4	28.6×	2e-04	KMT2D, KDM6A, KMT2B, KMT2A
PKMTs methylate histone lysines	3	48.2×	5e-04	KMT2D, KMT2B, KMT2A
Transcriptional regulation by RUNX1	3	43.9×	6e-04	KMT2D, KMT2B, KMT2A
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	3	36.1×	9e-04	KMT2D, KMT2B, KMT2A
Gene expression (Transcription)	5	8.9×	0.001	KMT2D, KDM6A, KMT2B, CCNT1, KMT2A
Activation of HOX genes during differentiation	2	87.8×	0.003	KMT2D, KDM6A
RNA Polymerase II Transcription	4	9.0×	0.007	KMT2D, KMT2B, CCNT1, KMT2A
Deactivation of the beta-catenin transactivating complex	2	46.6×	0.008	KMT2D, KMT2B
Defective ALG1 causes CDG-1k	1	1142.0×	0.008	ALG1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	2	43.1×	0.008	KMT2D, KDM6A
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	2	39.4×	0.009	KMT2D, KDM6A
Interactions of Tat with host cellular proteins	1	571.0×	0.013	CCNT1
Impaired BRCA2 translocation to the nucleus	1	380.7×	0.017	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	380.7×	0.017	BRCA2
Formation of the beta-catenin:TCF transactivating complex	2	24.0×	0.017	KMT2D, KMT2B
Generic Transcription Pathway	4	6.0×	0.017	KMT2D, KMT2B, CCNT1, KMT2A
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome	1	228.4×	0.024	KMT2D
Activation of anterior HOX genes in hindbrain development during early embryogenesis	2	18.3×	0.027	KMT2D, KDM6A
ARMS-mediated activation	1	163.1×	0.030	KIDINS220
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	2	16.6×	0.030	KMT2D, KDM6A
Prolonged ERK activation events	1	142.8×	0.032	KIDINS220
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	95.2×	0.047	BRCA2
HDR through MMEJ (alt-NHEJ)	1	87.8×	0.047	BRCA2
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	87.8×	0.047	KMT2A
Diseases of DNA Double-Strand Break Repair	1	81.6×	0.047	BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	81.6×	0.047	BRCA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
methylation	4	61.9×	3e-05	KMT2D, KMT2B, DNMT3B, KMT2A
beta-catenin-TCF complex assembly	1	1532.0×	0.018	KMT2D
positive regulation of DNA-templated transcription	4	10.2×	0.018	BRCA2, KMT2B, HCFC1, KMT2A
negative regulation of DNA methylation-dependent heterochromatin formation	1	766.0×	0.021	KMT2A
mitotic recombination-dependent replication fork processing	1	766.0×	0.021	BRCA2
release from viral latency	1	510.7×	0.027	HCFC1
oocyte growth	1	383.0×	0.031	KMT2D
negative regulation of mammary gland epithelial cell proliferation	1	306.4×	0.033	BRCA2
response to potassium ion	1	191.5×	0.036	KMT2A
establishment of protein localization to telomere	1	191.5×	0.036	BRCA2
regulation of DNA-templated transcription	3	8.6×	0.036	KMT2D, BRCA2, HCFC1
positive regulation of transcription by RNA polymerase II	4	5.4×	0.036	KMT2D, CCNT1, HCFC1, KMT2A
T-helper 2 cell differentiation	1	170.2×	0.037	KMT2A
response to UV-C	1	153.2×	0.037	BRCA2
telomere maintenance via recombination	1	139.3×	0.037	BRCA2
positive regulation of DNA-templated transcription, elongation	1	117.8×	0.037	CCNT1
nerve growth factor signaling pathway	1	117.8×	0.037	KIDINS220
positive regulation of intracellular estrogen receptor signaling pathway	1	109.4×	0.037	KMT2D
regulation of short-term neuronal synaptic plasticity	1	102.1×	0.037	KMT2A
regulation of DNA damage checkpoint	1	102.1×	0.037	BRCA2
inner cell mass cell proliferation	1	90.1×	0.037	BRCA2
embryonic hemopoiesis	1	90.1×	0.037	KMT2A
centrosome duplication	1	85.1×	0.037	BRCA2
definitive hemopoiesis	1	85.1×	0.037	KMT2A
response to X-ray	1	80.6×	0.037	BRCA2
host-mediated activation of viral transcription	1	80.6×	0.037	CCNT1
chromatin remodeling	2	13.3×	0.037	KDM6A, HCFC1
dolichol-linked oligosaccharide biosynthetic process	1	76.6×	0.038	ALG1
female gonad development	1	73.0×	0.039	BRCA2
regulation of cyclin-dependent protein serine/threonine kinase activity	1	66.6×	0.039	CCNT1

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 5 · Undrugged: 7

Druggability breadth: 9 of 12 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KDM6A	DEFERIPRONE
CCNT1	PALBOCICLIB
KMT2A	FLUORESCEIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KMT2A	535	4
CCNT1	34	4
KDM6A	1	4
DNMT3B	1	2
HCFC1	1	2
KMT2D	0	0
BRCA2	0	0
KMT2B	0	0
ALG1	0	0
ZBTB24	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DEFERIPRONE	4	KDM6A
PALBOCICLIB	4	CCNT1
ABEMACICLIB	4	CCNT1
RIBOCICLIB	4	CCNT1
TRILACICLIB	4	CCNT1
FLUORESCEIN	4	KMT2A
METHYSERGIDE	4	KMT2A
OXCARBAZEPINE	4	KMT2A
TRYPAN BLUE FREE ACID	4	KMT2A
RALOXIFENE HYDROCHLORIDE	4	KMT2A
IDARUBICIN	4	KMT2A
DULOXETINE	4	KMT2A
PYRITHIONE ZINC	4	KMT2A
HYDROCORTISONE VALERATE	4	KMT2A
PROMETHAZINE HYDROCHLORIDE	4	KMT2A
THIORIDAZINE HYDROCHLORIDE	4	KMT2A
METHYSERGIDE MALEATE	4	KMT2A
THIOTHIXENE	4	KMT2A
METHANTHELINE	4	KMT2A
ROSE BENGAL FREE ACID	4	KMT2A
BENZYL BENZOATE	4	KMT2A
NOMIFENSINE MALEATE	4	KMT2A
ANTAZOLINE	4	KMT2A
CARBOPLATIN	4	KMT2A
FLUVOXAMINE MALEATE	4	KMT2A
MITOXANTRONE HYDROCHLORIDE	4	KMT2A
ESTRADIOL VALERATE	4	KMT2A
EPHEDRINE SULFATE	4	KMT2A
DACTINOMYCIN	4	KMT2A
DAUNORUBICIN HYDROCHLORIDE	4	KMT2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CCNT1	617	Binding:614, ADMET:3
KMT2A	188	Binding:180, Functional:8
DNMT3B	76	Binding:75, Functional:1
KDM6A	40	Binding:36, Functional:4
KMT2B	15	Binding:15
KMT2D	11	Binding:11
HCFC1	8	Binding:8
ZBTB24	3	Binding:3
ALG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KDM6A	1.14.11.68	[histone H3]-trimethyl-L-lysine27 demethylase
ALG1	2.4.1.142	chitobiosyldiphosphodolichol beta-mannosyltransferase
DNMT3B	2.1.1.37	DNA (cytosine-5-)-methyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CCNT1	617
KMT2A	188

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
DEFERIPRONE	4	KDM6A
PALBOCICLIB	4	CCNT1
ABEMACICLIB	4	CCNT1
RIBOCICLIB	4	CCNT1
TRILACICLIB	4	CCNT1
FLUORESCEIN	4	KMT2A
METHYSERGIDE	4	KMT2A
OXCARBAZEPINE	4	KMT2A
TRYPAN BLUE FREE ACID	4	KMT2A
RALOXIFENE HYDROCHLORIDE	4	KMT2A
IDARUBICIN	4	KMT2A
DULOXETINE	4	KMT2A
PYRITHIONE ZINC	4	KMT2A
HYDROCORTISONE VALERATE	4	KMT2A
PROMETHAZINE HYDROCHLORIDE	4	KMT2A
THIORIDAZINE HYDROCHLORIDE	4	KMT2A
METHYSERGIDE MALEATE	4	KMT2A
THIOTHIXENE	4	KMT2A
METHANTHELINE	4	KMT2A
ROSE BENGAL FREE ACID	4	KMT2A
BENZYL BENZOATE	4	KMT2A
NOMIFENSINE MALEATE	4	KMT2A
ANTAZOLINE	4	KMT2A
CARBOPLATIN	4	KMT2A
FLUVOXAMINE MALEATE	4	KMT2A
MITOXANTRONE HYDROCHLORIDE	4	KMT2A
ESTRADIOL VALERATE	4	KMT2A
EPHEDRINE SULFATE	4	KMT2A
DACTINOMYCIN	4	KMT2A
DAUNORUBICIN HYDROCHLORIDE	4	KMT2A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	KDM6A, CCNT1, KMT2A
B	Phased (≥1) drug, not yet approved	2	DNMT3B, HCFC1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ALG1
E	Difficult family or no structure, no drug	6	KMT2D, BRCA2, KMT2B, ZBTB24, KIDINS220, ATP5MF-PTCD1

Undrugged target profiles

7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
KMT2D	11	KDM6A, KMT2A
KMT2B	15	KMT2A
ZBTB24	3	DNMT3B
BRCA2	0	—
ALG1	1	—
KIDINS220	0	—
ATP5MF-PTCD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03855631	Not specified	COMPLETED	Exploiting Epigenome Editing in Kabuki Syndrome: a New Route Towards Gene Therapy for Rare Genetic Disorders