Tessadori-van Haaften neurodevelopmental syndrome 2

Summary

Tessadori-van Haaften neurodevelopmental syndrome 2 (MONDO:0030730) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Tessadori-van Haaften neurodevelopmental syndrome 2
Mondo ID	MONDO:0030730
OMIM	619759
UMLS	C5676923
MedGen	1803228
Is cancer (heuristic)	no

Also known as: Tessadori-van Haaften neurodevelopmental syndrome 2 · TEVANED2

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Tessadori-Van-Haaften neurodevelopmental syndrome › Tessadori-van Haaften neurodevelopmental syndrome 2

Related subtypes (3): Tessadori-van Haaften neurodevelopmental syndrome 1, Tessadori-Van Haaften neurodevelopmental syndrome 3, Tessadori-Van Haaften neurodevelopmental syndrome 4

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

7 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1342159	NM_021968.4(H4C11):c.274A>G (p.Lys92Glu)	H4C11	Pathogenic	no assertion criteria provided
2681786	NM_021968.4(H4C11):c.106C>T (p.Arg36Trp)	H4C11	Likely pathogenic	criteria provided, single submitter
3236106	NM_021968.4(H4C11):c.284G>A (p.Gly95Asp)	H4C11	Uncertain significance	criteria provided, single submitter
3392541	NM_021968.4(H4C11):c.269C>G (p.Ala90Gly)	H4C11	Uncertain significance	criteria provided, single submitter
3393280	NM_021968.4(H4C11):c.248C>T (p.Thr83Ile)	H4C11	Uncertain significance	criteria provided, single submitter
4078904	NM_021968.4(H4C11):c.190G>T (p.Glu64Ter)	H4C11	Uncertain significance	criteria provided, single submitter
4293824	NM_021968.4(H4C11):c.97C>T (p.Pro33Ser)	H4C11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
H4C11	Moderate	Autosomal dominant	Tessadori-van Haaften neurodevelopmental syndrome 2	3

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
H4C11	HGNC:4785	ENSG00000197238	P62805	Histone H4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
H4C11	Histone H4	Core component of nucleosome.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
H4C11	Other/Unknown	no		Histone_H4, TAF_TATA-bd_Histone-like_dom, Histone-fold

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
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
H4C11	120	ubiquitous	marker	bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H4C11	4,216

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H4C11	P62805	626

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 60. 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
Replacement of protamines by nucleosomes in the male pronucleus	1	271.9×	0.012	H4C11
HDMs demethylate histones	1	228.4×	0.012	H4C11
Packaging Of Telomere Ends	1	219.6×	0.012	H4C11
Recognition and association of DNA glycosylase with site containing an affected purine	1	203.9×	0.012	H4C11
Cleavage of the damaged purine	1	203.9×	0.012	H4C11
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	1	184.2×	0.012	H4C11
Cleavage of the damaged pyrimidine	1	184.2×	0.012	H4C11
RNA Polymerase I Promoter Opening	1	184.2×	0.012	H4C11
ChAHP complex assembly	1	184.2×	0.012	H4C11
DNA methylation	1	178.4×	0.012	H4C11
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.012	H4C11
SIRT1 negatively regulates rRNA expression	1	170.4×	0.012	H4C11
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	1	167.9×	0.012	H4C11
Nonhomologous End-Joining (NHEJ)	1	167.9×	0.012	H4C11
Inhibition of DNA recombination at telomere	1	167.9×	0.012	H4C11
Assembly of the ORC complex at the origin of replication	1	165.5×	0.012	H4C11
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.012	H4C11
Chromatin modifications during the maternal to zygotic transition (MZT)	1	163.1×	0.012	H4C11
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	1	163.1×	0.012	H4C11
PKMTs methylate histone lysines	1	160.8×	0.012	H4C11
SUMOylation of chromatin organization proteins	1	158.6×	0.012	H4C11
Deposition of new CENPA-containing nucleosomes at the centromere	1	158.6×	0.012	H4C11
Condensation of Prophase Chromosomes	1	156.4×	0.012	H4C11
Defective pyroptosis	1	156.4×	0.012	H4C11
PRC2 methylates histones and DNA	1	152.3×	0.012	H4C11
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	152.3×	0.012	H4C11
CHD6, CHD7, CHD8, CHD9 subfamily	1	148.3×	0.012	H4C11
RMTs methylate histone arginines	1	146.4×	0.012	H4C11
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.012	H4C11
Transcriptional regulation by small RNAs	1	144.6×	0.012	H4C11

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
protein localization to CENP-A containing chromatin	1	936.2×	0.003	H4C11
negative regulation of megakaryocyte differentiation	1	887.0×	0.003	H4C11
telomere organization	1	624.1×	0.003	H4C11
nucleosome assembly	1	140.4×	0.009	H4C11
chromatin organization	1	99.1×	0.010	H4C11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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
H4C11	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMREDOBRESIB	2	H4C11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
H4C11	14	Binding:14

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

1 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)
AMREDOBRESIB	2	H4C11

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	H4C11
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.