Menke-Hennekam syndrome 2

Summary

Menke-Hennekam syndrome 2 (MONDO:0020769) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 65

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Menke-Hennekam syndrome 2
Mondo ID	MONDO:0020769
OMIM	618333
UMLS	C5193035
MedGen	1676668
GARD	0025243
Is cancer (heuristic)	no

Also known as: Menke-Hennekam syndrome 2 · MKHK2

Data availability: 65 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Menke-Hennekam syndrome › Menke-Hennekam syndrome 2

Related subtypes (1): Menke-Hennekam syndrome 1

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

65 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 13 conflicting classifications of pathogenicity, 6 benign/likely benign, 6 benign, 6 likely pathogenic, 3 likely benign, 2 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
137620	NM_001429.4(EP300):c.104_107del (p.Ser35fs)	EP300	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210941	NM_001429.4(EP300):c.6915_6918del (p.Asn2305fs)	EP300	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
619096	NM_001429.4(EP300):c.5489GGA[1] (p.Arg1831del)	EP300	Pathogenic	no assertion criteria provided
2503425	NM_001429.4(EP300):c.3139_3140del (p.Lys1047fs)	EP300	Likely pathogenic	no assertion criteria provided
2580919	NM_001429.4(EP300):c.4898T>G (p.Leu1633Arg)	EP300	Likely pathogenic	criteria provided, single submitter
3251937	NM_001429.4(EP300):c.369_370dup (p.Ser124fs)	EP300	Likely pathogenic	criteria provided, single submitter
3366946	NM_001429.4(EP300):c.5366GCT[1] (p.Cys1790del)	EP300	Likely pathogenic	criteria provided, single submitter
619095	NM_001429.4(EP300):c.5471A>C (p.Gln1824Pro)	EP300	Likely pathogenic	criteria provided, single submitter
973766	NM_001429.4(EP300):c.7111T>A (p.Ser2371Thr)	EP300	Likely pathogenic	criteria provided, single submitter
1049476	NM_001429.4(EP300):c.695G>C (p.Gly232Ala)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1215031	NM_001429.4(EP300):c.5926C>T (p.Pro1976Ser)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1236178	NM_001429.4(EP300):c.1303G>A (p.Val435Ile)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1350847	NM_001429.4(EP300):c.454G>A (p.Gly152Ser)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1476622	NM_001429.4(EP300):c.4756G>T (p.Ala1586Ser)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2393470	NM_001429.4(EP300):c.772A>G (p.Thr258Ala)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2653205	NM_001429.4(EP300):c.3815G>C (p.Cys1272Ser)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2703841	NM_001429.4(EP300):c.1366G>A (p.Val456Ile)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2732794	NM_001429.4(EP300):c.3872A>C (p.Lys1291Thr)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
595659	NM_001429.4(EP300):c.5683C>T (p.Pro1895Ser)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
803699	NM_001429.4(EP300):c.3624C>G (p.Ile1208Met)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931160	NM_001429.4(EP300):c.1760+20C>T	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
977155	NM_001429.4(EP300):c.1781C>T (p.Thr594Met)	EP300	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030398	NM_001429.4(EP300):c.6786G>C (p.Gln2262His)	EP300	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341708	NM_001429.4(EP300):c.2960C>T (p.Pro987Leu)	EP300	Uncertain significance	criteria provided, single submitter
1343262	NM_001429.4(EP300):c.4372C>T (p.Pro1458Ser)	EP300	Uncertain significance	criteria provided, single submitter
1699491	NM_001429.4(EP300):c.1985C>A (p.Ala662Glu)	EP300	Uncertain significance	criteria provided, single submitter
1709924	NM_001429.4(EP300):c.5192G>A (p.Arg1731His)	EP300	Uncertain significance	criteria provided, single submitter
2431613	NM_001429.4(EP300):c.4021G>A (p.Ala1341Thr)	EP300	Uncertain significance	criteria provided, single submitter
2633319	NM_001429.4(EP300):c.6435_6446dup (p.Gln2153_Leu2154insProGlnGlnGln)	EP300	Uncertain significance	criteria provided, multiple submitters, no conflicts
3235079	NM_001429.4(EP300):c.1225C>T (p.His409Tyr)	EP300	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EP300	Orphanet:353284	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EP300	HGNC:3373	ENSG00000100393	Q09472	Histone acetyltransferase p300	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EP300	Histone acetyltransferase p300	Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EP300	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
bone marrow cell	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EP300	292	ubiquitous	marker	colonic epithelium, adrenal tissue, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EP300	10,122

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EP300	Q09472	60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 62. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	2284.0×	0.005	EP300
NFE2L2 regulating inflammation associated genes	1	2284.0×	0.005	EP300
NFE2L2 regulating ER-stress associated genes	1	2284.0×	0.005	EP300
NFE2L2 regulates pentose phosphate pathway genes	1	1427.5×	0.005	EP300
NFE2L2 regulating MDR associated enzymes	1	1427.5×	0.005	EP300
Regulation of NFE2L2 gene expression	1	1427.5×	0.005	EP300
PI5P Regulates TP53 Acetylation	1	1268.9×	0.005	EP300
RUNX3 regulates p14-ARF	1	1142.0×	0.005	EP300
Regulation of FOXO transcriptional activity by acetylation	1	1142.0×	0.005	EP300
STAT3 nuclear events downstream of ALK signaling	1	1038.2×	0.005	EP300
Regulation of gene expression by Hypoxia-inducible Factor	1	951.7×	0.005	EP300
NOTCH2 intracellular domain regulates transcription	1	951.7×	0.005	EP300
Activation of the TFAP2 (AP-2) family of transcription factors	1	951.7×	0.005	EP300
NFE2L2 regulating tumorigenic genes	1	951.7×	0.005	EP300
RUNX3 regulates NOTCH signaling	1	815.7×	0.005	EP300
TRAF3-dependent IRF activation pathway	1	761.3×	0.005	EP300
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	713.8×	0.005	EP300
FOXO-mediated transcription of cell death genes	1	713.8×	0.005	EP300
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	671.8×	0.005	EP300
Zygotic genome activation (ZGA)	1	671.8×	0.005	EP300
Polo-like kinase mediated events	1	634.4×	0.005	EP300
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	601.0×	0.005	EP300
NOTCH4 Intracellular Domain Regulates Transcription	1	571.0×	0.005	EP300
Regulation of TP53 Activity through Methylation	1	543.8×	0.005	EP300
NFE2L2 regulating anti-oxidant/detoxification enzymes	1	543.8×	0.005	EP300
CD209 (DC-SIGN) signaling	1	519.1×	0.005	EP300
Regulation of TP53 Activity through Acetylation	1	456.8×	0.005	EP300
TGFBR3 expression	1	456.8×	0.005	EP300
NOTCH3 Intracellular Domain Regulates Transcription	1	439.2×	0.005	EP300
Attenuation phase	1	407.9×	0.005	EP300

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
behavioral defense response	1	16852.0×	5e-04	EP300
negative regulation of protein oligomerization	1	16852.0×	5e-04	EP300
swimming	1	16852.0×	5e-04	EP300
peptidyl-lysine propionylation	1	16852.0×	5e-04	EP300
regulation of tubulin deacetylation	1	16852.0×	5e-04	EP300
peptidyl-lysine crotonylation	1	16852.0×	5e-04	EP300
peptidyl-lysine butyrylation	1	16852.0×	5e-04	EP300
internal protein amino acid acetylation	1	8426.0×	9e-04	EP300
N-terminal peptidyl-lysine acetylation	1	5617.3×	0.001	EP300
thigmotaxis	1	4213.0×	0.001	EP300
negative regulation of chromosome condensation	1	4213.0×	0.001	EP300
internal peptidyl-lysine acetylation	1	3370.4×	0.002	EP300
negative regulation of brown fat cell differentiation	1	2808.7×	0.002	EP300
positive regulation of TORC2 signaling	1	2106.5×	0.002	EP300
positive regulation of T-helper 17 cell lineage commitment	1	2106.5×	0.002	EP300
protein acetylation	1	1404.3×	0.003	EP300
cellular response to L-leucine	1	1404.3×	0.003	EP300
regulation of glycolytic process	1	1203.7×	0.003	EP300
regulation of cellular response to heat	1	1053.2×	0.003	EP300
regulation of androgen receptor signaling pathway	1	991.3×	0.003	EP300
host-mediated activation of viral transcription	1	887.0×	0.003	EP300
regulation of mitochondrion organization	1	842.6×	0.003	EP300
negative regulation of gluconeogenesis	1	802.5×	0.003	EP300
stimulatory C-type lectin receptor signaling pathway	1	732.7×	0.003	EP300
platelet formation	1	702.2×	0.003	EP300
megakaryocyte development	1	702.2×	0.003	EP300
DNA repair-dependent chromatin remodeling	1	674.1×	0.003	EP300
obsolete positive regulation of DNA-binding transcription factor activity	1	601.9×	0.004	EP300
positive regulation of transforming growth factor beta receptor signaling pathway	1	526.6×	0.004	EP300
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	495.6×	0.004	EP300

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EP300	9	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COENZYME_A	3	EP300
CURCUMIN	3	EP300
EPIGALOCATECHIN GALLATE	3	EP300
MOLIBRESIB	2	EP300
MIVEBRESIB	2	EP300
STREPTONIGRIN	2	EP300
BERBERINE CHLORIDE	1	EP300
PLUMBAGIN	1	EP300
INOBRODIB	1	EP300

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EP300	767	Binding:763, Functional:3, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EP300	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EP300	767

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

9 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)
COENZYME_A	3	EP300
CURCUMIN	3	EP300
EPIGALOCATECHIN GALLATE	3	EP300
MOLIBRESIB	2	EP300
MIVEBRESIB	2	EP300
STREPTONIGRIN	2	EP300
BERBERINE CHLORIDE	1	EP300
PLUMBAGIN	1	EP300
INOBRODIB	1	EP300

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	EP300
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.