Pontocerebellar hypoplasia, type 16

disease

On this page

Also known as PCH16

Summary

Pontocerebellar hypoplasia, type 16 (MONDO:0030438) is a disease caused by MINPP1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: MINPP1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pontocerebellar hypoplasia, type 16
Mondo ID	MONDO:0030438
OMIM	619527
DOID	DOID:0112333
UMLS	C5561987
MedGen	1794197
GARD	0025561
Is cancer (heuristic)	no

Also known as: PCH16

Data availability: 22 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 16

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

22 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 7 likely pathogenic, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1801152	NM_004897.5(MINPP1):c.1401del (p.Ser468fs)	LOC126860990	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1285618	NM_004897.5(MINPP1):c.223_224insGGGGG (p.Glu75fs)	LOC130004261	Pathogenic	no assertion criteria provided
1285620	NM_004897.5(MINPP1):c.300del (p.Lys101fs)	MINPP1	Pathogenic	no assertion criteria provided
1285621	NM_004897.5(MINPP1):c.75_94del (p.Leu27fs)	MINPP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3377176	NM_004897.5(MINPP1):c.903G>A (p.Trp301Ter)	MINPP1	Pathogenic	criteria provided, single submitter
1285623	NM_004897.5(MINPP1):c.1210C>T (p.Arg404Ter)	LOC126860990	Likely pathogenic	criteria provided, single submitter
4082278	NM_004897.5(MINPP1):c.204G>A (p.Trp68Ter)	LOC130004261	Likely pathogenic	criteria provided, single submitter
1285619	NM_004897.5(MINPP1):c.157T>G (p.Tyr53Asp)	MINPP1	Likely pathogenic	criteria provided, single submitter
1325784	NM_004897.5(MINPP1):c.851C>A (p.Ala284Asp)	MINPP1	Likely pathogenic	criteria provided, single submitter
3064384	NM_004897.5(MINPP1):c.940G>T (p.Glu314Ter)	MINPP1	Likely pathogenic	criteria provided, single submitter
3775954	NM_004897.5(MINPP1):c.1097_1098del (p.Leu366fs)	MINPP1	Likely pathogenic	criteria provided, single submitter
4082279	NM_004897.5(MINPP1):c.422G>A (p.Trp141Ter)	MINPP1	Likely pathogenic	criteria provided, single submitter
1285624	NM_004897.5(MINPP1):c.992T>G (p.Ile331Ser)	MINPP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1285622	NM_004897.5(MINPP1):c.1456G>A (p.Glu486Lys)	LOC126860990	Uncertain significance	criteria provided, single submitter
1526394	NM_004897.5(MINPP1):c.1202G>A (p.Arg401Gln)	LOC126860990	Uncertain significance	criteria provided, single submitter
1342137	NM_004897.5(MINPP1):c.1008C>G (p.Ser336Arg)	MINPP1	Uncertain significance	criteria provided, single submitter
1526393	NM_004897.5(MINPP1):c.682T>C (p.Phe228Leu)	MINPP1	Uncertain significance	criteria provided, single submitter
3064832	NM_004897.5(MINPP1):c.56T>C (p.Leu19Pro)	MINPP1	Uncertain significance	criteria provided, single submitter
3891662	NM_004897.5(MINPP1):c.1063C>T (p.Gln355Ter)	MINPP1	Uncertain significance	criteria provided, single submitter
3891663	NM_004897.5(MINPP1):c.125C>T (p.Ser42Leu)	MINPP1	Uncertain significance	criteria provided, single submitter
3891664	NM_004897.5(MINPP1):c.991A>G (p.Ile331Val)	MINPP1	Uncertain significance	criteria provided, single submitter
4082280	NM_004897.5(MINPP1):c.1299_1304dup (p.Gln435_Met436insValGln)	MINPP1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
MINPP1	Strong	Autosomal recessive	pontocerebellar hypoplasia, type 16	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MINPP1	Orphanet:284339	Pontocerebellar hypoplasia type 7
MINPP1	Orphanet:319487	Familial papillary or follicular thyroid carcinoma

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
MINPP1	HGNC:7102	ENSG00000107789	Q9UNW1	Multiple inositol polyphosphate phosphatase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MINPP1	Multiple inositol polyphosphate phosphatase 1	Multiple inositol polyphosphate phosphatase that hydrolyzes 1D-myo-inositol 1,3,4,5,6-pentakisphosphate (InsP5[2OH]) and 1D-myo-inositol hexakisphosphate (InsP6) to a range of less phosphorylated inositol phosphates.

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)
MINPP1	Enzyme (other)	yes	3.1.3.62	His_Pase_clade-2, Histidine_acid_Pase_euk, His_PPase_superfam

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
adrenal tissue	1
tibia	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MINPP1	275	ubiquitous	marker	trabecular bone tissue, tibia, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MINPP1	821

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MINPP1	Q9UNW1	90.42

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
Synthesis of IPs in the ER lumen	1	11420.0×	3e-04	MINPP1
Inositol phosphate metabolism	1	475.8×	0.003	MINPP1
Metabolism	1	11.6×	0.086	MINPP1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intracellular monoatomic cation homeostasis	1	1123.5×	0.002	MINPP1
inositol phosphate metabolic process	1	991.3×	0.002	MINPP1
bone mineralization	1	271.8×	0.004	MINPP1
ossification	1	227.7×	0.004	MINPP1

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
MINPP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MINPP1	3.1.3.62	multiple inositol-polyphosphate phosphatase

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	1	MINPP1
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)
MINPP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: MINPP1