MINPP1

protein-coding

multiple inositol-polyphosphate phosphatase 1, the group of MicroRNA protein coding host genes|Phosphoinositide phosphatases

Gene summary

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]

MANE transcript

NM_004897.5

Inheritance

ClinVar variants

P:17U:70B:21

Top phenotype

Pontocerebellar hypoplasia, type 16

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr10:87,504,875-87,553,461

External References & Databases

Ensembl (ENSG00000107789)

Transcript & Mutation Effects

hg38 • Region Span ~48.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pontocerebellar hypoplasiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020135

Submitter: ClinGen

*MINPP1* was first reported in relation to autosomal recessive pontocerebellar hypoplasia in 2020 (Appelhof et al., PMID: 33168985). This condition is characterized by severe global developmental delay, microcephaly, brain structural anomalies (such as cerebellar, cerebral cortical, pontine, and thalamic hypoplasia), intellectual disability, motor complications, lack of/unclear speech, epilepsy, axial hypotonia, stereotypies, and facial dysmorphism. Sixteen variants (missense, nonsense, frameshift) that have been reported in at least 16 probands in 5 publications (PMIDs: 33168985, 33257696, 35568357, 40508022, 41025723) are included in this curation. The maximum score for genetic evidence (12 pts.) has been reached. This gene-disease relationship is also supported by experimental evidence (mouse, HEK293 cell, and patient fibroblast models; PMIDs: 10938126, 33257696). Experimental data shows that the gene is key in maintaining cell growth and phosphate homeostasis. In summary, there is definitive evidence supporting the relationship between MINPP1 and autosomal recessive pontocerebellar hypoplasia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Cerebral Palsy GCEP on the meeting date March 16th, 2026 (SOP Version 12).

pontocerebellar hypoplasia, type 16STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030438

Submitter: Labcorp Genetics (formerly Invitae)

pontocerebellar hypoplasia, type 16STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030438

Submitter: G2P

thyroid cancer, nonmedullary, 2NO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0008566

Submitter: Labcorp Genetics (formerly Invitae)

pontocerebellar hypoplasia, type 16STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030438

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Pontocerebellar hypoplasia, type 16AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33168985; 33257696

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MINPP1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 69

Pontocerebellar hypoplasia, type 16Total: 22

not providedTotal: 14

Thyroid cancer, nonmedullary, 2Total: 5

MINPP1-related disorderTotal: 4

Pontoneocerebellar hypoplasiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004897.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				12 clinvar	2 clinvar	14
missense	2 clinvar	3 clinvar	67 clinvar	7 clinvar		79
nonsense	1 clinvar	4 clinvar	2 clinvar			7
start loss						0
frameshift	3 clinvar	4 clinvar				7
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	6	11	70	19	2	108

Highest pathogenic variant AF is 0.000008214508

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004897.5	RefSeq	NP_004888.2	5	MANE Select
ENST00000371996.9	Ensembl	ENSP00000361064.4	5	MANE Select
NM_001178117.2	RefSeq	NP_001171588.1	3	Standard
NM_001178118.2	RefSeq	NP_001171589.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycolysis / Gluconeogenesis - Homo sapiens (human)
Inositol phosphate metabolism - Homo sapiens (human)
Inositol Phosphate Metabolism
Inositol Metabolism
D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis

Biological Process

ossification
protein dephosphorylation
polyphosphate metabolic process
bone mineralization
inositol phosphate metabolic process

Molecular Function

acid phosphatase activity
inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity
bisphosphoglycerate 3-phosphatase activity
inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
inositol phosphate phosphatase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371996
Coding exons: 5
Length: 48586
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.579	240	267	0.900	0.0000125	3151
Missense (PolyPhen)		51	82.298	0.6197		1020
Synonymous	0.0160	112	112	0.998	0.00000543	983
Loss of Function	2.38	9	20.7	0.435	0.00000113	229

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000083	0.000079	rare
South Asian	0.000067	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a phosphoinositide 5- and phosphoinositide 6- phosphatase and regulates cellular levels of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Also acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to produce phospho-D-glycerate without formation of 3- phosphoglycerate. May play a role in bone development (endochondral ossification). May play a role in the transition of chondrocytes from proliferation to hypertrophy (By similarity). {ECO:0000250|UniProtKB:F1NPQ2, ECO:0000269|PubMed:18413611}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.414
RVIS EVS: -0.63
RVIS percentile EVS: 17.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium