pontocerebellar hypoplasia type 2C

disease

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Also known as non-syndromic pontocerebellar hypoplasia caused by mutation in TSEN34PCH2Cpontocerebellar hypoplasia, type 2CTSEN34 non-syndromic pontocerebellar hypoplasia

Summary

pontocerebellar hypoplasia type 2C (MONDO:0012891) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pontocerebellar hypoplasia type 2C
Mondo ID	MONDO:0012891
MeSH	C567324
OMIM	612390
DOID	DOID:0060269
UMLS	C2676465
MedGen	382856
GARD	0015554
Is cancer (heuristic)	no

Also known as: non-syndromic pontocerebellar hypoplasia caused by mutation in TSEN34 · PCH2C · pontocerebellar hypoplasia, type 2C · TSEN34 non-syndromic pontocerebellar hypoplasia

Data availability: 5 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 disorder › spinal cord disorder › anterior horn disorder › spinal muscular atrophy › bulbospinal muscular atrophy › pontocerebellar hypoplasia type 2 › pontocerebellar hypoplasia type 2C

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

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2124	NM_001077446.4(TSEN34):c.172C>T (p.Arg58Trp)	TSEN34	Pathogenic	no assertion criteria provided
804160	NM_001077446.4(TSEN34):c.862_865dup (p.Leu289fs)	TSEN34	Likely pathogenic	criteria provided, single submitter
160121	NM_001077446.4(TSEN34):c.468G>C (p.Ser156=)	TSEN34	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212447	NM_001077446.4(TSEN34):c.392C>T (p.Ser131Leu)	TSEN34	Uncertain significance	criteria provided, multiple submitters, no conflicts
3367039	NM_001077446.4(TSEN34):c.905C>T (p.Thr302Ile)	TSEN34	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
TSEN34	Supportive	Autosomal recessive	pontocerebellar hypoplasia type 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSEN34	Orphanet:2524	Pontocerebellar hypoplasia type 2

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
TSEN34	HGNC:15506	ENSG00000170892	Q9BSV6	tRNA-splicing endonuclease subunit Sen34	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSEN34	tRNA-splicing endonuclease subunit Sen34	Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSEN34	Enzyme (other)	yes	4.6.1.16	tRNA_splic, tRNA_intron_Endonuc_cat-like, tRNA_endonuc-like_dom_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
blood	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSEN34	140	ubiquitous	marker	blood, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSEN34	680

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSEN34	Q9BSV6	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
tRNA processing	1	356.9×	0.008	TSEN34
tRNA processing in the nucleus	1	196.9×	0.008	TSEN34
Metabolism of RNA	1	41.7×	0.024	TSEN34

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-type intron splice site recognition and cleavage	1	5617.3×	4e-04	TSEN34
mRNA processing	1	78.8×	0.013	TSEN34

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSEN34	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TSEN34	4.6.1.16	tRNA-intron lyase

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	1	TSEN34
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
TSEN34	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TSEN34