Pontocerebellar hypoplasia, type 11

disease

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Also known as PCH11Pontocerebellar hypoplasia due to TBC1D23

Summary

Pontocerebellar hypoplasia, type 11 (MONDO:0054669) is a disease caused by TBC1D23 (GenCC Definitive), with 1 cohort gene.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: TBC1D23 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	pontocerebellar hypoplasia, type 11
Mondo ID	MONDO:0054669
OMIM	617695
Orphanet	611247
DOID	DOID:0112324
UMLS	C4540164
MedGen	1627627
GARD	0018029
Is cancer (heuristic)	no

Also known as: PCH11 · Pontocerebellar hypoplasia due to TBC1D23 · pontocerebellar hypoplasia, type 11

Data availability: 26 ClinVar variants · 2 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 11

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

26 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 9 pathogenic, 2 benign, 2 likely pathogenic, 2 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323676	NM_001199198.3(TBC1D23):c.1092+2T>A	TBC1D23	Pathogenic	criteria provided, single submitter
1325171	NM_001199198.3(TBC1D23):c.614_615del (p.Phe205fs)	TBC1D23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503049	NM_001199198.3(TBC1D23):c.1018del (p.Val340fs)	TBC1D23	Pathogenic	criteria provided, single submitter
397553	NM_001199198.3(TBC1D23):c.1475_1476del (p.Val492fs)	TBC1D23	Pathogenic	no assertion criteria provided
397554	NM_001199198.3(TBC1D23):c.1526delinsAA (p.Ile509fs)	TBC1D23	Pathogenic	no assertion criteria provided
397555	NM_001199198.3(TBC1D23):c.1687+2T>G	TBC1D23	Pathogenic	no assertion criteria provided
4293118	NM_001199198.3(TBC1D23):c.743_744del (p.Gln248fs)	TBC1D23	Pathogenic	criteria provided, single submitter
440764	NM_001199198.3(TBC1D23):c.1687+1G>A	TBC1D23	Pathogenic	no assertion criteria provided
4845334	NM_001199198.3(TBC1D23):c.667C>T (p.Gln223Ter)	TBC1D23	Pathogenic	criteria provided, single submitter
930943	NM_001199198.3(TBC1D23):c.1687+1G>C	TBC1D23	Pathogenic	criteria provided, single submitter
987034	NM_001199198.3(TBC1D23):c.951_954del (p.Cys317fs)	TBC1D23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323675	NM_001199198.3(TBC1D23):c.630del (p.Thr211fs)	TBC1D23	Likely pathogenic	criteria provided, single submitter
440763	NM_001199198.3(TBC1D23):c.1687+2T>A	TBC1D23	Likely pathogenic	criteria provided, single submitter
1029243	NM_001199198.3(TBC1D23):c.1327G>A (p.Asp443Asn)	TBC1D23	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029244	NM_001199198.3(TBC1D23):c.170C>T (p.Ala57Val)	TBC1D23	Uncertain significance	criteria provided, single submitter
1031925	NM_001199198.3(TBC1D23):c.1883G>T (p.Gly628Val)	TBC1D23	Uncertain significance	criteria provided, single submitter
1031926	NM_001199198.3(TBC1D23):c.538C>T (p.Pro180Ser)	TBC1D23	Uncertain significance	criteria provided, single submitter
1065496	NM_001199198.3(TBC1D23):c.1004G>T (p.Gly335Val)	TBC1D23	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436958	NM_001199198.3(TBC1D23):c.53+100G>A	TBC1D23	Uncertain significance	criteria provided, single submitter
2436959	NM_001199198.3(TBC1D23):c.1505G>A (p.Arg502Lys)	TBC1D23	Uncertain significance	criteria provided, single submitter
2503503	NM_001199198.3(TBC1D23):c.458T>C (p.Met153Thr)	TBC1D23	Uncertain significance	criteria provided, single submitter
4080518	NM_001199198.3(TBC1D23):c.1399A>G (p.Ile467Val)	TBC1D23	Uncertain significance	criteria provided, single submitter
4293255	NM_001199198.3(TBC1D23):c.1000-8C>A	TBC1D23	Uncertain significance	criteria provided, single submitter
1251837	NM_001199198.3(TBC1D23):c.876+27G>T	TBC1D23	Benign	criteria provided, multiple submitters, no conflicts
1334928	NM_001199198.3(TBC1D23):c.1554-49dup	TBC1D23	Benign	criteria provided, single submitter
801991	NM_001199198.3(TBC1D23):c.92G>C (p.Cys31Ser)	TBC1D23	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
TBC1D23	Definitive	Autosomal recessive	pontocerebellar hypoplasia, type 11	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
TBC1D23	HGNC:25622	ENSG00000036054	Q9NUY8	TBC1 domain family member 23	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBC1D23	TBC1 domain family member 23	Putative Rab GTPase-activating protein which plays a role in vesicular trafficking.

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)
TBC1D23	Other/Unknown	no		Rab-GAP-TBC_dom, Rhodanese-like_dom, Rab-GAP_TBC_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
cardiac muscle of right atrium	1
ileal mucosa	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBC1D23	253	ubiquitous	marker	cardiac muscle of right atrium, left ventricle myocardium, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBC1D23	1,023

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBC1D23	Q9NUY8	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
obsolete vesicle tethering to Golgi	1	3370.4×	0.002	TBC1D23
embryonic brain development	1	802.5×	0.004	TBC1D23
retrograde transport, endosome to Golgi	1	205.5×	0.010	TBC1D23
neuron projection development	1	122.1×	0.012	TBC1D23
vesicle-mediated transport	1	96.3×	0.012	TBC1D23
brain development	1	79.5×	0.013	TBC1D23

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
TBC1D23	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	TBC1D23

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)
TBC1D23	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TBC1D23