pontocerebellar hypoplasia, type 1D

disease

On this page

Also known as PCH1D

Summary

pontocerebellar hypoplasia, type 1D (MONDO:0054844) is a disease caused by EXOSC9 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: EXOSC9 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pontocerebellar hypoplasia, type 1D
Mondo ID	MONDO:0054844
OMIM	618065
DOID	DOID:0112323
UMLS	C4748058
MedGen	1648387
GARD	0016289
Is cancer (heuristic)	no

Also known as: PCH1D · pontocerebellar hypoplasia, type 1D

Data availability: 14 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system malformation › pontocerebellar hypoplasia › pontocerebellar hypoplasia, type 1D

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

14 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic/likely pathogenic, 4 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1397502	NM_005033.3(EXOSC9):c.685C>T (p.Arg229Ter)	EXOSC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687055	NM_005033.3(EXOSC9):c.239T>G (p.Leu80Arg)	EXOSC9	Pathogenic	no assertion criteria provided
1687056	NM_005033.3(EXOSC9):c.484dup (p.Arg162fs)	EXOSC9	Pathogenic	no assertion criteria provided
1687057	NM_005033.3(EXOSC9):c.151G>C (p.Gly51Arg)	EXOSC9	Pathogenic	no assertion criteria provided
2143770	NM_005033.3(EXOSC9):c.634C>T (p.Arg212Ter)	EXOSC9	Pathogenic	criteria provided, multiple submitters, no conflicts
2578183	NM_005033.3(EXOSC9):c.20C>G (p.Ser7Ter)	EXOSC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
549845	NM_005033.3(EXOSC9):c.41T>C (p.Leu14Pro)	EXOSC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
549846	NM_005033.3(EXOSC9):c.481C>T (p.Arg161Ter)	EXOSC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3385106	NM_005033.3(EXOSC9):c.827+1G>A	EXOSC9	Likely pathogenic	criteria provided, single submitter
1309898	NM_005033.3(EXOSC9):c.538C>T (p.Arg180Cys)	EXOSC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1313162	NM_005033.3(EXOSC9):c.390G>T (p.Trp130Cys)	EXOSC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1359781	NM_005033.3(EXOSC9):c.263C>T (p.Pro88Leu)	EXOSC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
3255122	NM_005033.3(EXOSC9):c.545C>T (p.Pro182Leu)	EXOSC9	Uncertain significance	criteria provided, single submitter
3902001	NM_005033.3(EXOSC9):c.97A>G (p.Arg33Gly)	EXOSC9	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
EXOSC9	Strong	Autosomal recessive	pontocerebellar hypoplasia, type 1D	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EXOSC9	Orphanet:2254	Pontocerebellar hypoplasia type 1

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
EXOSC9	HGNC:9137	ENSG00000123737	Q06265	Exosome complex component RRP45	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EXOSC9	Exosome complex component RRP45	Non-catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EXOSC9	Scaffold/PPI	no		ExoRNase_PH_dom1, ExoRNase_PH_dom2, Ribosomal_Su5_D2-typ_SF

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
calcaneal tendon	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EXOSC9	285	ubiquitous	marker	secondary oocyte, oocyte, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EXOSC9	2,532

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EXOSC9	Q06265	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
mRNA decay by 3’ to 5’ exoribonuclease	1	713.8×	0.003	EXOSC9
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	1	634.4×	0.003	EXOSC9
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	1	634.4×	0.003	EXOSC9
KSRP (KHSRP) binds and destabilizes mRNA	1	634.4×	0.003	EXOSC9
ATF4 activates genes in response to endoplasmic reticulum stress	1	407.9×	0.003	EXOSC9
Nuclear RNA decay	1	308.6×	0.004	EXOSC9
Major pathway of rRNA processing in the nucleolus and cytosol	1	61.7×	0.016	EXOSC9

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
U1 snRNA 3’-end processing	1	5617.3×	0.001	EXOSC9
U5 snRNA 3’-end processing	1	5617.3×	0.001	EXOSC9
exonucleolytic trimming to generate mature 3’-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	2407.4×	0.001	EXOSC9
nuclear polyadenylation-dependent rRNA catabolic process	1	2407.4×	0.001	EXOSC9
TRAMP-dependent tRNA surveillance pathway	1	2407.4×	0.001	EXOSC9
U4 snRNA 3’-end processing	1	2106.5×	0.001	EXOSC9
nuclear mRNA surveillance	1	1872.4×	0.001	EXOSC9
rRNA catabolic process	1	991.3×	0.002	EXOSC9
nuclear-transcribed mRNA catabolic process	1	766.0×	0.002	EXOSC9
mRNA catabolic process	1	495.6×	0.003	EXOSC9
RNA catabolic process	1	455.5×	0.003	EXOSC9
RNA processing	1	218.9×	0.006	EXOSC9
positive regulation of cell growth	1	183.2×	0.007	EXOSC9
rRNA processing	1	141.6×	0.008	EXOSC9
immune response	1	47.1×	0.023	EXOSC9
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	EXOSC9

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
EXOSC9	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	EXOSC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
EXOSC9	7	Binding:7

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)
MOLIBRESIB	2	EXOSC9

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	EXOSC9
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.

Cohort genes: EXOSC9