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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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MINPP1
multiple inositol-polyphosphate phosphatase 1
Chromosome 10 Β· 10q23.2
NCBI Gene: 9562Ensembl: ENSG00000107789.16HGNC: HGNC:7102UniProt: Q9UNW1
47PubMed Papers
22Diseases
0Drugs
16Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activityintracellular monoatomic cation homeostasisinositol hexakisphosphate phosphatase activityprotein bindingpontocerebellar hypoplasia, type 16pontocerebellar hypoplasiafollicular thyroid carcinomathyroid cancer, nonmedullary, 2
✦AI Summary

MINPP1 (multiple inositol-polyphosphate phosphatase 1) is a histidine phosphatase that hydrolyzes highly phosphorylated inositol polyphosphates, particularly inositol hexakisphosphate (IP6) and inositol pentakisphosphate, into less phosphorylated derivatives 1. By regulating inositol polyphosphate pools, MINPP1 controls the availability of intracellular calcium and iron, which are critical for neuronal development and homeostasis 2. Additionally, MINPP1 exhibits dual substrate specificity, functioning as a 2,3-bisphosphoglycerate 3-phosphatase in glycolytic regulation 3. Loss-of-function MINPP1 mutations cause pontocerebellar hypoplasia type 16 (PCH16), characterized by accumulation of IP6 and subsequent pathological metal chelation that impairs neuronal differentiation and causes brain atrophy 2, 4. MINPP1 variants are also associated with follicular thyroid carcinoma, where LOH at the MINPP1 locus occurs in approximately 25% of tumors, potentially acting as a low-penetrance predisposition allele 5. Recent evidence demonstrates MINPP1 promotes ferroptosis in hepatitis B virus-associated hepatocellular carcinoma via the MINPP1-ZRANB1-CTSB axis 3. MINPP1 expression increases under cellular stress conditions and influences apoptotic responses 6. Higher MINPP1 plasma levels correlate with improved CD4+ T-cell recovery in HIV-positive patients receiving antiretroviral therapy 7.

Sources cited
1
MINPP1 prevents IP6 accumulation; loss-of-function mutations cause pontocerebellar hypoplasia with impaired neuronal differentiation and ion homeostasis defects
PMID: 33257696
2
Biallelic MINPP1 loss-of-function variants cause PCH16 with elevated lipid levels and disrupted inositol metabolism
PMID: 40508022
3
MINPP1 is a histidine phosphatase that hydrolyzes inositol pentakisphosphate and hexakisphosphate; localized to chromosome 10q23
PMID: 10087200
4
MINPP1 LOH occurs in ~25% of follicular thyroid tumors; somatic and germline variants suggest role in follicular thyroid carcinoma pathogenesis
PMID: 11297621
5
MINPP1 promotes ferroptosis in HBV-related hepatocellular carcinoma through the MINPP1-ZRANB1-CTSB axis via glycolytic bypass mechanism
PMID: 41035046
6
MINPP1 expression increases under cellular stress conditions and may promote ER stress-induced apoptosis
PMID: 27038811
7
High plasma MINPP1 levels correlate with better CD4+ T-cell recovery in HIV-positive patients on antiretroviral therapy
PMID: 35920599
Disease Associationsβ“˜22
pontocerebellar hypoplasia, type 16Open Targets
0.76Strong
pontocerebellar hypoplasiaOpen Targets
0.61Moderate
follicular thyroid carcinomaOpen Targets
0.56Moderate
thyroid cancer, nonmedullary, 2Open Targets
0.47Moderate
neurodegenerative diseaseOpen Targets
0.42Moderate
pontocerebellar hypoplasia type 7Open Targets
0.37Weak
Non-syndromic pontocerebellar hypoplasiaOpen Targets
0.35Weak
Thyroid adenomaOpen Targets
0.33Weak
cutaneous melanomaOpen Targets
0.25Weak
bipolar disorderOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
periodontitisOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.05Suggestive
hypothyroidismOpen Targets
0.04Suggestive
migraine disorderOpen Targets
0.03Suggestive
glioblastomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.01Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
Pontocerebellar hypoplasia 16UniProt
Thyroid cancer, non-medullary, 2UniProt
Pathogenic Variants16
NM_004897.5(MINPP1):c.75_94del (p.Leu27fs)Pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜…β˜†β˜†2025β†’ Residue 27
NM_004897.5(MINPP1):c.1401del (p.Ser468fs)Pathogenic
not provided|Pontocerebellar hypoplasia, type 16
β˜…β˜…β˜†β˜†2024β†’ Residue 468
NM_004897.5(MINPP1):c.422G>A (p.Trp141Ter)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2025β†’ Residue 141
NM_004897.5(MINPP1):c.204G>A (p.Trp68Ter)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2025β†’ Residue 68
NM_004897.5(MINPP1):c.903G>A (p.Trp301Ter)Pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2024β†’ Residue 301
NM_004897.5(MINPP1):c.940G>T (p.Glu314Ter)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2024β†’ Residue 314
NM_004897.5(MINPP1):c.1097_1098del (p.Leu366fs)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2023β†’ Residue 366
NM_004897.5(MINPP1):c.687dup (p.Asp230Ter)Likely pathogenic
MINPP1-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 230
NM_004897.5(MINPP1):c.157T>G (p.Tyr53Asp)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2022β†’ Residue 53
NM_004897.5(MINPP1):c.851C>A (p.Ala284Asp)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2021β†’ Residue 284
NM_004897.5(MINPP1):c.1210C>T (p.Arg404Ter)Likely pathogenic
Pontocerebellar hypoplasia, type 16
β˜…β˜†β˜†β˜†2021β†’ Residue 404
NM_004897.5(MINPP1):c.1027_1028del (p.Ile343fs)Pathogenic
Pontoneocerebellar hypoplasia
β˜…β˜†β˜†β˜†β†’ Residue 343
NM_004897.5(MINPP1):c.300del (p.Lys101fs)Pathogenic
Pontocerebellar hypoplasia, type 16
β˜†β˜†β˜†β˜†2022β†’ Residue 101
NM_004897.5(MINPP1):c.223_224insGGGGG (p.Glu75fs)Pathogenic
Pontocerebellar hypoplasia, type 16
β˜†β˜†β˜†β˜†2022β†’ Residue 75
NM_004897.5(MINPP1):c.122C>T (p.Ser41Leu)Pathogenic
Thyroid cancer, nonmedullary, 2
β˜†β˜†β˜†β˜†2001β†’ Residue 41
NM_004897.5(MINPP1):c.809A>G (p.Gln270Arg)Pathogenic
Thyroid cancer, nonmedullary, 2
β˜†β˜†β˜†β˜†2001β†’ Residue 270
View on ClinVar β†—
Related Genes
TALDO1Protein interaction100%GPIProtein interaction100%ALDOAProtein interaction97%PLCG2Protein interaction96%DERAProtein interaction96%H6PDProtein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
60%
Brain
25%
Ovary
21%
Lung
20%
Heart
17%
Gene Interaction Network
Click a node to explore
MINPP1TALDO1GPIALDOAPLCG2DERAH6PD
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9UNW1
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.77LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.38–0.77]
RankingsWhere MINPP1 stands among ~20K protein-coding genes
  • #9,238of 20,598
    Most Researched47
  • #2,415of 5,498
    Most Pathogenic Variants16
  • #6,170of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedMINPP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Somatic mutation and germline variants of MINPP1, a phosphatase gene located in proximity to PTEN on 10q23.3, in follicular thyroid carcinomas.
PMID: 11297621
J Clin Endocrinol Metab Β· 2001
1.00
2
MINPP1 promotes ferroptosis in HBV-related hepatocellular carcinoma by regulating CTSB K33-linked deubiquitination via ZRANB1.
PMID: 41035046
Biol Direct Β· 2025
0.90
3
MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia.
PMID: 33257696
Nat Commun Β· 2020
0.80
4
Biallelic Loss-of-Function Variant in
PMID: 40508022
Int J Mol Sci Β· 2025
0.70
5
Clinical and genetic characterization of patients segregating variants in KPTN, MINPP1, NGLY1, AP4B1, and SON underlying neurodevelopmental disorders: Genetic and phenotypic expansion.
PMID: 36181241
Int J Dev Neurosci Β· 2022
0.60