Bryant-Li-Bhoj neurodevelopmental syndrome 1

Summary

Bryant-Li-Bhoj neurodevelopmental syndrome 1 (MONDO:0030606) is a disease caused by H3-3A (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: H3-3A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bryant-Li-Bhoj neurodevelopmental syndrome 1
Mondo ID	MONDO:0030606
OMIM	619720
DOID	DOID:0051011
UMLS	C5676905
MedGen	1801103
GARD	0027929
Is cancer (heuristic)	no

Also known as: BRYLIB1

Data availability: 19 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 › Bryant-Li-Bhoj neurodevelopmental syndrome › Bryant-Li-Bhoj neurodevelopmental syndrome 1

Related subtypes (1): Bryant-Li-Bhoj neurodevelopmental 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

19 retrieved; paginated sample, class counts are floors:

5 pathogenic/likely pathogenic, 4 uncertain significance, 4 likely pathogenic, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1183977	NM_002107.7(H3-3A):c.121C>T (p.Arg41Cys)	H3-3A	Pathogenic/Likely pathogenic	no assertion criteria provided
1183980	NM_002107.7(H3-3A):c.363G>A (p.Met121Ile)	H3-3A	Pathogenic	criteria provided, multiple submitters, no conflicts
1183981	NM_002107.7(H3-3A):c.386G>A (p.Arg129His)	H3-3A	Pathogenic/Likely pathogenic	no assertion criteria provided
1339283	NM_002107.7(H3-3A):c.52A>G (p.Arg18Gly)	H3-3A	Pathogenic	criteria provided, single submitter
3343880	NM_002107.7(H3-3A):c.68C>T (p.Thr23Ile)	H3-3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376608	NM_002107.7(H3-3A):c.362T>C (p.Met121Thr)	H3-3A	Pathogenic	criteria provided, single submitter
520774	NM_002107.7(H3-3A):c.377A>G (p.Gln126Arg)	H3-3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
985335	NM_002107.7(H3-3A):c.137C>T (p.Thr46Ile)	H3-3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4291940	NM_002107.7(H3-3A):c.339C>G (p.Ile113Met)	H3-3A	Likely pathogenic	criteria provided, single submitter
4755433	NM_002107.7(H3-3A):c.148C>T (p.Arg50Cys)	H3-3A	Likely pathogenic	criteria provided, single submitter
983132	NM_002107.7(H3-3A):c.250C>G (p.Arg84Gly)	H3-3A	Likely pathogenic	criteria provided, single submitter
985263	NM_002107.7(H3-3A):c.326A>G (p.Asn109Ser)	H3-3A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
690374	NM_002107.7(H3-3A):c.365C>T (p.Pro122Leu)	H3-3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
985386	NM_002107.7(H3-3A):c.337A>G (p.Ile113Val)	H3-3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1183979	NM_002107.7(H3-3A):c.271G>C (p.Gly91Arg)	H3-3A	Uncertain significance	criteria provided, single submitter
2444025	NM_002107.7(H3-3A):c.137C>A (p.Thr46Asn)	H3-3A	Uncertain significance	criteria provided, single submitter
3062006	NM_002107.7(H3-3A):c.134G>A (p.Gly45Asp)	H3-3A	Uncertain significance	criteria provided, single submitter
3381184	NM_002107.7(H3-3A):c.388C>T (p.Arg130Cys)	H3-3A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4074293	NM_002107.7(H3-3A):c.244G>A (p.Asp82Asn)	H3-3A	not provided	no classification provided

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
H3-3A	Definitive	Autosomal dominant	Bryant-Li-Bhoj neurodevelopmental syndrome 1	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
H3-3A	HGNC:4764	ENSG00000163041	P84243	Histone H3.3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
H3-3A	Histone H3.3	Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.

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)
H3-3A	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, 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
ganglionic eminence	1
monocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
H3-3A	134	ubiquitous	marker	ganglionic eminence, monocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H3-3A	1,595

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H3-3A	P84243	103

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. 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	H3-3A
RNA Polymerase I Promoter Opening	1	184.2×	0.012	H3-3A
DNA methylation	1	178.4×	0.012	H3-3A
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.012	H3-3A
SIRT1 negatively regulates rRNA expression	1	170.4×	0.012	H3-3A
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	1	167.9×	0.012	H3-3A
Inhibition of DNA recombination at telomere	1	167.9×	0.012	H3-3A
Assembly of the ORC complex at the origin of replication	1	165.5×	0.012	H3-3A
Chromatin modifications during the maternal to zygotic transition (MZT)	1	163.1×	0.012	H3-3A
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	1	163.1×	0.012	H3-3A
Condensation of Prophase Chromosomes	1	156.4×	0.012	H3-3A
Defective pyroptosis	1	156.4×	0.012	H3-3A
PRC2 methylates histones and DNA	1	152.3×	0.012	H3-3A
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	152.3×	0.012	H3-3A
CHD6, CHD7, CHD8, CHD9 subfamily	1	148.3×	0.012	H3-3A
Transcriptional regulation by small RNAs	1	144.6×	0.012	H3-3A
NuRD complex assembly	1	141.0×	0.012	H3-3A
Meiotic recombination	1	129.8×	0.012	H3-3A
Interaction of NuRD complexes with transcription factors	1	126.9×	0.012	H3-3A
Transcriptional regulation of granulopoiesis	1	125.5×	0.012	H3-3A
Pre-NOTCH Transcription and Translation	1	122.8×	0.012	H3-3A
B-WICH complex positively regulates rRNA expression	1	121.5×	0.012	H3-3A
RNA Polymerase I Promoter Escape	1	121.5×	0.012	H3-3A
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.012	H3-3A
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.012	H3-3A
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.012	H3-3A
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.012	H3-3A
Regulation of PD-L1(CD274) transcription	1	108.8×	0.012	H3-3A
CHD1 and CHD2 subfamily	1	108.8×	0.012	H3-3A
Regulation of endogenous retroelements by KRAB-ZFP proteins	1	106.7×	0.012	H3-3A

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
negative regulation of chromosome condensation	1	4213.0×	0.002	H3-3A
pericentric heterochromatin formation	1	3370.4×	0.002	H3-3A
subtelomeric heterochromatin formation	1	1532.0×	0.003	H3-3A
muscle cell differentiation	1	842.6×	0.004	H3-3A
telomere organization	1	624.1×	0.004	H3-3A
oocyte maturation	1	601.9×	0.004	H3-3A
nucleus organization	1	561.7×	0.004	H3-3A
embryo implantation	1	351.1×	0.006	H3-3A
single fertilization	1	183.2×	0.008	H3-3A
positive regulation of cell growth	1	183.2×	0.008	H3-3A
male gonad development	1	156.0×	0.008	H3-3A
spermatid development	1	145.3×	0.008	H3-3A
nucleosome assembly	1	140.4×	0.008	H3-3A
multicellular organism growth	1	137.0×	0.008	H3-3A
osteoblast differentiation	1	121.2×	0.009	H3-3A
cell population proliferation	1	102.8×	0.010	H3-3A

Therapeutics

Drug target analysis

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

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
H3-3A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
H3-3A	6	Binding:6

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	H3-3A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
H3-3A	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.