MINPP1

Chr 10ADSomaticAR

multiple inositol-polyphosphate phosphatase 1

Also known as: HIPER1, MINPP2, MIPP, PCH16

NCBI Gene: 9562ENSG00000107789UniProt: Q9UNW1

This gene encodes multiple inositol polyphosphate phosphatase; an enzyme that removes 3-phosphate from inositol phosphate substrates. It is the only enzyme known to hydrolzye inositol pentakisphosphate and inositol hexakisphosphate. This enzyme also converts 2,3 bisphosphoglycerate (2,3-BPG) to 2-phosphoglycerate; an activity formerly thought to be exclusive to 2,3-BPG synthase/2-phosphatase (BPGM) in the Rapoport-Luebering shunt of the glycolytic pathway.[provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

{Thyroid carcinoma, follicular}MIM #188470
ADSomatic
Pontocerebellar hypoplasia, type 16MIM #619527
AR
UniProtThyroid cancer, non-medullary, 2
131
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MINPP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 68 VUS of 131 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.76LOEUF
pLI 0.000
Z-score 2.38
OE 0.44 (0.26–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.58Z-score
OE missense 0.90 (0.81–1.00)
240 obs / 266.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.26–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 9 / 20.7Missense obs/exp: 240 / 266.6Syn Z: 0.02

ClinVar Variant Classifications

131 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic10
VUS68
Likely Benign15
Benign6
Conflicting1
31
Pathogenic
10
Likely Pathogenic
68
VUS
15
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
26
0
31
Likely Pathogenic
3
2
5
0
10
VUS
0
65
3
0
68
Likely Benign
0
9
0
6
15
Benign
0
0
4
2
6
Conflicting
—1
Total678388131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MINPP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Thyroid carcinoma, follicular}

MIM #188470

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Pontocerebellar hypoplasia, type 16

MIM #619527

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biallelic Loss-of-Function Variant in MINPP1 Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder.
Al-Maraghi A et al.·Int J Mol Sci
2025Case report
Clinical and genetic characterization of patients segregating variants in KPTN, MINPP1, NGLY1, AP4B1, and SON underlying neurodevelopmental disorders: Genetic and phenotypic expansion.
Ullah A et al.·Int J Dev Neurosci
2022Cohort
Somatic mutation and germline variants of MINPP1, a phosphatase gene located in proximity to PTEN on 10q23.3, in follicular thyroid carcinomas.
Gimm O et al.·J Clin Endocrinol Metab
2001
MINPP1 -Related Pontocerebellar Hypoplasia in Five New Patients: Identification of Three Novel Variants and Further Phenotype Delineation.
Abdel-Ghafar SF et al.·Clin Genet
2026Case report
Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing.
Masih S et al.·Eur J Med Genet
2022
Hepatitis B virus P protein initiates glycolytic bypass in HBV-related hepatocellular carcinoma via a FOXO3/miRNA-30b-5p/MINPP1 axis.
Chen W et al.·J Exp Clin Cancer Res
2021
Identification of Antitumor miR-30e-5p Controlled Genes; Diagnostic and Prognostic Biomarkers for Head and Neck Squamous Cell Carcinoma.
Minemura C et al.·Genes (Basel)
2022
A family with juvenile polyposis linked to the BMPR1A locus: cryptic mutation or closely linked gene?
Chow E et al.·J Gastroenterol Hepatol
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools