Hemiparkinsonism-hemiatrophy syndrome

Summary

Hemiparkinsonism-hemiatrophy syndrome (MONDO:0017636) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		68	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001269	Hemiparesis	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001300	Parkinsonism	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0006801	Hyperactive deep tendon reflexes	Frequent (30-79%)
HP:0006956	Dilation of lateral ventricles	Frequent (30-79%)
HP:0011331	Hemifacial atrophy	Frequent (30-79%)
HP:0012444	Brain atrophy	Frequent (30-79%)
HP:0012768	Neonatal asphyxia	Frequent (30-79%)
HP:0100556	Hemiatrophy	Frequent (30-79%)
HP:0000716	Depression	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0100308	Cerebral cortical hemiatrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hemiparkinsonism-hemiatrophy syndrome
Mondo ID	MONDO:0017636
Orphanet	306669
ICD-11	193784690
UMLS	C4545231
MedGen	1627807
GARD	0021262
Is cancer (heuristic)	no

Also known as: Hp-HA syndrome

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › parkinsonian disorder › hemiparkinsonism-hemiatrophy syndrome

Related subtypes (20): postencephalitic Parkinson disease, Parkinson disease, dystonia 12, Perry syndrome, X-linked parkinsonism-spasticity syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked dystonia-parkinsonism, autosomal dominant striatal neurodegeneration type 1, dystonia 16, parkinsonism-dystonia, infantile, cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome, carbon monoxide-induced parkinsonism, cyanide-induced parkinsonism, atypical juvenile parkinsonism, primary progressive freezing gait, encephalitis lethargica, parkinsonism with dementia of Guadeloupe, multiple system atrophy, parkinsonian type, parkinsonism with polyneuropathy, vascular parkinsonism

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
986385	NM_005324.5(H3-3B):c.354C>A (p.Val118=)	H3-3B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
H3-3B	HGNC:4765	ENSG00000132475	P84243	Histone H3.3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
H3-3B	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)
H3-3B	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
oocyte	1
secondary oocyte	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
H3-3B	308	ubiquitous	marker	oocyte, secondary oocyte, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H3-3B	1,595

Structural data

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

Cohort genes with PDB structures (top 30)

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

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

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
H3-3B	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
H3-3B	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	H3-3B

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)
H3-3B	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.