pontocerebellar hypoplasia, type 2F

disease

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Also known as non-syndromic pontocerebellar hypoplasia caused by mutation in TSEN15PCH2Fpontocerebellar hypoplasia, type 2FTSEN15 non-syndromic pontocerebellar hypoplasia

Summary

pontocerebellar hypoplasia, type 2F (MONDO:0014874) is a disease caused by TSEN15 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: TSEN15 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pontocerebellar hypoplasia, type 2F
Mondo ID	MONDO:0014874
OMIM	617026
DOID	DOID:0112329
UMLS	C4310757
MedGen	934724
GARD	0016178
Is cancer (heuristic)	no

Also known as: non-syndromic pontocerebellar hypoplasia caused by mutation in TSEN15 · PCH2F · pontocerebellar hypoplasia, type 2F · pontocerebellar hypoplasia, type 2F; PCH2F · TSEN15 non-syndromic pontocerebellar hypoplasia

Data availability: 4 ClinVar variants · 3 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 2F

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
243000	NM_052965.4(TSEN15):c.455A>G (p.Tyr152Cys)	TSEN15	Pathogenic	no assertion criteria provided
243001	NM_052965.4(TSEN15):c.346C>T (p.His116Tyr)	TSEN15	Likely pathogenic	criteria provided, single submitter
183315	NM_052965.4(TSEN15):c.226T>G (p.Trp76Gly)	TSEN15	Uncertain significance	criteria provided, single submitter
3574697	NM_052965.4(TSEN15):c.192C>G (p.Phe64Leu)	TSEN15	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
TSEN15	Strong	Autosomal recessive	pontocerebellar hypoplasia, type 2F	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSEN15	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
TSEN15	HGNC:16791	ENSG00000198860	Q8WW01	tRNA-splicing endonuclease subunit Sen15	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSEN15	tRNA-splicing endonuclease subunit Sen15	Non-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)
TSEN15	Enzyme (other)	yes	4.6.1.16	tRNA_endonuc-like_dom_sf, tRNA-endonuc_su_Sen15, tRNA_intron_Endo_cat-like_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
C1 segment of cervical spinal cord	1
cardiac muscle of right atrium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSEN15	253	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSEN15	851

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSEN15	Q8WW01	7

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	TSEN15
tRNA processing in the nucleus	1	196.9×	0.008	TSEN15
Metabolism of RNA	1	41.7×	0.024	TSEN15

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tRNA splicing, via endonucleolytic cleavage and ligation	1	1404.3×	0.001	TSEN15
mRNA processing	1	78.8×	0.013	TSEN15

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
TSEN15	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TSEN15	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	TSEN15
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)
TSEN15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TSEN15