pontocerebellar hypoplasia type 2B
diseaseOn this page
Also known as non-syndromic pontocerebellar hypoplasia caused by mutation in TSEN2PCH2Bpontocerebellar hypoplasia, type 2BTSEN2 non-syndromic pontocerebellar hypoplasia
Summary
pontocerebellar hypoplasia type 2B (MONDO:0012890) is a disease caused by TSEN2 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: TSEN2 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 33
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | pontocerebellar hypoplasia type 2B |
| Mondo ID | MONDO:0012890 |
| MeSH | C567325 |
| OMIM | 612389 |
| DOID | DOID:0060268 |
| UMLS | C2676466 |
| MedGen | 393505 |
| GARD | 0015553 |
| Is cancer (heuristic) | no |
Also known as: non-syndromic pontocerebellar hypoplasia caused by mutation in TSEN2 · PCH2B · pontocerebellar hypoplasia type 2B · pontocerebellar hypoplasia, type 2B · TSEN2 non-syndromic pontocerebellar hypoplasia
Data availability: 33 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 2B
Related subtypes (4): pontocerebellar hypoplasia type 2A, pontocerebellar hypoplasia type 2C, pontocerebellar hypoplasia type 2D, 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
33 retrieved; paginated sample, class counts are floors:
11 likely pathogenic, 11 uncertain significance, 5 conflicting classifications of pathogenicity, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1031439 | NM_025265.4(TSEN2):c.770_776delinsCA (p.Tyr257fs) | TSEN2 | Pathogenic | criteria provided, single submitter |
| 180670 | NM_025265.4(TSEN2):c.934G>A (p.Gly312Arg) | TSEN2 | Pathogenic | no assertion criteria provided |
| 180671 | NM_025265.4(TSEN2):c.691C>T (p.Gln231Ter) | TSEN2 | Pathogenic | no assertion criteria provided |
| 2682520 | NM_025265.4(TSEN2):c.958A>T (p.Lys320Ter) | TSEN2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3251458 | NM_025265.4(TSEN2):c.57C>A (p.Tyr19Ter) | TSEN2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1334772 | NM_025265.4(TSEN2):c.904G>A (p.Glu302Lys) | TSEN2 | Likely pathogenic | no assertion criteria provided |
| 180669 | NM_025265.4(TSEN2):c.960+1_960+5del | TSEN2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 212442 | NM_025265.4(TSEN2):c.1337A>G (p.Gln446Arg) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 212443 | NM_025265.4(TSEN2):c.138CAA[1] (p.Asn48del) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 3588355 | NM_025265.4(TSEN2):c.200del (p.Gly67fs) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 3588357 | NM_025265.4(TSEN2):c.580C>T (p.Gln194Ter) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 3588358 | NM_025265.4(TSEN2):c.695_699del (p.Arg232fs) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 4814061 | NM_025265.4(TSEN2):c.1260_1264del (p.Cys421fs) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 495252 | NM_025265.4(TSEN2):c.1037A>G (p.Tyr346Cys) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 495253 | NM_025265.4(TSEN2):c.353_354del (p.Gln118fs) | TSEN2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 632396 | NM_025265.4(TSEN2):c.1048C>T (p.Arg350Ter) | TSEN2 | Likely pathogenic | criteria provided, single submitter |
| 1334773 | NM_025265.4(TSEN2):c.1354C>T (p.Arg452Ter) | TSEN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 160101 | NM_025265.4(TSEN2):c.1013C>G (p.Thr338Arg) | TSEN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 160105 | NM_025265.4(TSEN2):c.1272T>C (p.Ile424=) | TSEN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 160108 | NM_025265.4(TSEN2):c.1389C>T (p.Asp463=) | TSEN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2125 | NM_025265.4(TSEN2):c.926A>G (p.Tyr309Cys) | TSEN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 160111 | NM_025265.4(TSEN2):c.322G>T (p.Val108Phe) | TSEN2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 160114 | NM_025265.4(TSEN2):c.608C>T (p.Thr203Ile) | TSEN2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 160115 | NM_025265.4(TSEN2):c.653C>T (p.Pro218Leu) | TSEN2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 212444 | NM_025265.4(TSEN2):c.431A>G (p.Asn144Ser) | TSEN2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2437385 | NM_025265.4(TSEN2):c.1016T>G (p.Phe339Cys) | TSEN2 | Uncertain significance | criteria provided, single submitter |
| 2444490 | NM_025265.4(TSEN2):c.23C>A (p.Ala8Asp) | TSEN2 | Uncertain significance | criteria provided, single submitter |
| 2573067 | NM_025265.4(TSEN2):c.1087G>A (p.Gly363Arg) | TSEN2 | Uncertain significance | criteria provided, single submitter |
| 2573068 | NM_025265.4(TSEN2):c.1355G>T (p.Arg452Leu) | TSEN2 | Uncertain significance | criteria provided, single submitter |
| 2690283 | NM_025265.4(TSEN2):c.703CAT[1] (p.His236del) | TSEN2 | 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 |
|---|---|---|---|---|
| TSEN2 | Strong | Autosomal recessive | pontocerebellar hypoplasia type 2B | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TSEN2 | 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 |
|---|---|---|---|---|---|
| TSEN2 | HGNC:28422 | ENSG00000154743 | Q8NCE0 | tRNA-splicing endonuclease subunit Sen2 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TSEN2 | tRNA-splicing endonuclease subunit Sen2 | 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) |
|---|---|---|---|---|
| TSEN2 | Enzyme (other) | yes | 4.6.1.16 | tRNA_splic, tRNA_intron_Endonuc_cat-like, tRNA_intron_Endonuc_N |
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 |
|---|---|
| buccal mucosa cell | 1 |
| mucosa of transverse colon | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TSEN2 | 225 | ubiquitous | marker | buccal mucosa cell, mucosa of transverse colon, primordial germ cell in gonad |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TSEN2 | 1,088 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TSEN2 | Q8NCE0 | 5 |
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 | TSEN2 |
| tRNA processing in the nucleus | 1 | 196.9× | 0.008 | TSEN2 |
| Metabolism of RNA | 1 | 41.7× | 0.024 | TSEN2 |
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 |
|---|---|---|---|---|
| tRNA-type intron splice site recognition and cleavage | 1 | 5617.3× | 7e-04 | TSEN2 |
| tRNA splicing, via endonucleolytic cleavage and ligation | 1 | 1404.3× | 0.001 | TSEN2 |
| tRNA processing | 1 | 842.6× | 0.002 | TSEN2 |
| mRNA processing | 1 | 78.8× | 0.013 | TSEN2 |
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 |
|---|---|---|
| TSEN2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| TSEN2 | 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 | TSEN2 |
| 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) |
|---|---|---|
| TSEN2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: TSEN2