pontocerebellar hypoplasia, type 1E

disease

On this page

Also known as PCH1E

Summary

pontocerebellar hypoplasia, type 1E (MONDO:0030260) is a disease caused by SLC25A46 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: SLC25A46 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pontocerebellar hypoplasia, type 1E
Mondo ID	MONDO:0030260
OMIM	619303
DOID	DOID:0112330
UMLS	C5543328
MedGen	1788285
GARD	0016441
Is cancer (heuristic)	no

Also known as: PCH1E · pontocerebellar hypoplasia, type 1E

Data availability: 15 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 1E

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

15 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 likely pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068765	NM_138773.4(SLC25A46):c.691C>T (p.Arg231Ter)	SLC25A46	Pathogenic	no assertion criteria provided
1068766	NM_138773.4(SLC25A46):c.326+549_385-1240del	SLC25A46	Pathogenic	no assertion criteria provided
1068768	NM_138773.4(SLC25A46):c.42C>G (p.Tyr14Ter)	SLC25A46	Pathogenic	no assertion criteria provided
372241	NM_138773.4(SLC25A46):c.998C>T (p.Pro333Leu)	SLC25A46	Pathogenic	criteria provided, single submitter
372242	NM_138773.4(SLC25A46):c.1018C>T (p.Arg340Cys)	SLC25A46	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374892	NM_138773.4(SLC25A46):c.1022T>C (p.Leu341Pro)	SLC25A46	Pathogenic	no assertion criteria provided
374894	NM_138773.4(SLC25A46):c.425C>T (p.Thr142Ile)	SLC25A46	Pathogenic	no assertion criteria provided
422422	NM_138773.4(SLC25A46):c.11_12insTG (p.Arg5fs)	SLC25A46	Pathogenic	criteria provided, multiple submitters, no conflicts
938735	NM_138773.4(SLC25A46):c.462+1G>A	SLC25A46	Pathogenic	criteria provided, single submitter
1334589	NM_138773.4(SLC25A46):c.479G>A (p.Trp160Ter)	SLC25A46	Likely pathogenic	criteria provided, single submitter
3382951	NM_138773.4(SLC25A46):c.674T>G (p.Val225Gly)	SLC25A46	Likely pathogenic	criteria provided, single submitter
372240	NM_138773.4(SLC25A46):c.882_885dup (p.Asn296fs)	SLC25A46	Likely pathogenic	criteria provided, single submitter
488599	NM_138773.4(SLC25A46):c.736A>T (p.Arg246Ter)	SLC25A46	Likely pathogenic	criteria provided, single submitter
542451	NM_138773.4(SLC25A46):c.148C>A (p.Pro50Thr)	SLC25A46	Uncertain significance	criteria provided, multiple submitters, no conflicts
641936	NM_138773.4(SLC25A46):c.620+4_620+7del	SLC25A46	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
SLC25A46	Strong	Autosomal recessive	pontocerebellar hypoplasia, type 1E	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A46	Orphanet:2254	Pontocerebellar hypoplasia type 1
SLC25A46	Orphanet:90120	Hereditary motor and sensory neuropathy type 6

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
SLC25A46	HGNC:25198	ENSG00000164209	Q96AG3	Mitochondrial outer membrane protein SLC25A46	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A46	Mitochondrial outer membrane protein SLC25A46	Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization.

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)
SLC25A46	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf, SLC25A46

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
oocyte	1
secondary oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A46	290	ubiquitous	marker	sperm, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A46	1,557

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC25A46	Q96AG3	1

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
mitochondrial membrane fission	1	8426.0×	0.002	SLC25A46
peripheral nervous system neuron axonogenesis	1	4213.0×	0.002	SLC25A46
respiratory chain complex IV assembly	1	2407.4×	0.002	SLC25A46
locomotion involved in locomotory behavior	1	2407.4×	0.002	SLC25A46
mitochondrial transport	1	1203.7×	0.002	SLC25A46
optic nerve development	1	1203.7×	0.002	SLC25A46
mitochondrial fission	1	1053.2×	0.002	SLC25A46
cerebellar Purkinje cell differentiation	1	1053.2×	0.002	SLC25A46
cristae formation	1	1053.2×	0.002	SLC25A46
phospholipid homeostasis	1	991.3×	0.002	SLC25A46
myelination in peripheral nervous system	1	887.0×	0.002	SLC25A46
autophagy of mitochondrion	1	732.7×	0.002	SLC25A46
axon development	1	455.5×	0.003	SLC25A46
dendrite development	1	391.9×	0.003	SLC25A46
synapse assembly	1	230.8×	0.005	SLC25A46
protein-containing complex assembly	1	113.9×	0.009	SLC25A46

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
SLC25A46	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	SLC25A46

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)
SLC25A46	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: SLC25A46