MINPP1

Summary

MINPP1 (multiple inositol-polyphosphate phosphatase 1, HGNC:7102) is a protein-coding gene on chromosome 10q23.2, encoding Multiple inositol polyphosphate phosphatase 1 (Q9UNW1). 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.

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.

Source: NCBI Gene 9562 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 74 total — 5 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 78
• MANE Select transcript: NM_004897

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7102
Approved symbol	MINPP1
Name	multiple inositol-polyphosphate phosphatase 1
Location	10q23.2
Locus type	gene with protein product
Status	Approved
Aliases	MIPP
Ensembl gene	ENSG00000107789
Ensembl biotype	protein_coding
OMIM	605391
Entrez	9562

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371994, ENST00000371996, ENST00000472891, ENST00000536010

RefSeq mRNA: 3 — MANE Select: NM_004897 NM_001178117, NM_001178118, NM_004897

CCDS: CCDS53551, CCDS53552, CCDS7384

Canonical transcript exons

ENST00000371996 — 5 exons

Exon	Start	End
ENSE00000909241	87521036	87521169
ENSE00000909242	87513124	87513221
ENSE00000909243	87508336	87508533
ENSE00003579773	87552082	87553461
ENSE00003843154	87504893	87505552

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 93.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.0848 / max 615.7832, expressed in 1801 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106019	20.6566	1789
106018	4.4282	1628

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	93.63	gold quality
tibia	UBERON:0000979	92.01	gold quality
adrenal tissue	UBERON:0018303	91.68	gold quality
islet of Langerhans	UBERON:0000006	89.81	gold quality
choroid plexus epithelium	UBERON:0003911	89.72	gold quality
jejunal mucosa	UBERON:0000399	89.53	gold quality
right adrenal gland cortex	UBERON:0035827	88.87	gold quality
right adrenal gland	UBERON:0001233	88.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.45	gold quality
nephron tubule	UBERON:0001231	88.45	gold quality
left adrenal gland	UBERON:0001234	88.33	gold quality
stromal cell of endometrium	CL:0002255	88.05	gold quality
right lobe of liver	UBERON:0001114	88.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.87	gold quality
left adrenal gland cortex	UBERON:0035825	87.62	gold quality
adrenal gland	UBERON:0002369	87.61	gold quality
placenta	UBERON:0001987	87.60	gold quality
adrenal cortex	UBERON:0001235	87.48	gold quality
colonic mucosa	UBERON:0000317	87.44	gold quality
ventricular zone	UBERON:0003053	87.41	gold quality
bone marrow	UBERON:0002371	87.34	gold quality
germinal epithelium of ovary	UBERON:0001304	87.29	gold quality
ganglionic eminence	UBERON:0004023	86.71	gold quality
pigmented layer of retina	UBERON:0001782	86.64	gold quality
duodenum	UBERON:0002114	86.53	gold quality
liver	UBERON:0002107	86.42	gold quality
cartilage tissue	UBERON:0002418	86.28	gold quality
parietal pleura	UBERON:0002400	85.73	gold quality
visceral pleura	UBERON:0002401	85.60	gold quality
pancreas	UBERON:0001264	85.33	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	210.54
E-HCAD-4	yes	138.28
E-MTAB-10042	yes	31.02
E-MTAB-9067	yes	20.37
E-ANND-3	yes	10.01
E-HCAD-9	yes	6.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting MINPP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734

Literature-anchored findings (GeneRIF, showing 4)

• By RNA knockdown, we identified secreted and lysosome targeted MINPP1 (multiple inositol-polyphosphate phosphatase 1), the mammalian 3-phytase, to be essentially involved both in extracellular and in lysosomal InsP6 dephosphorylation (PMID:23186306)
• Minpp1 exhibits characteristics of a stress responsive molecule during Endoplasmic reticulum stress-induced apoptosis (PMID:27038811)
• Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1. (PMID:33168985)
• MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia. (PMID:33257696)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	minpp1b	ENSDARG00000045172
danio_rerio	minpp1a	ENSDARG00000057058
mus_musculus	Minpp1	ENSMUSG00000024896
rattus_norvegicus	Minpp1	ENSRNOG00000011287
rattus_norvegicus		ENSRNOG00000081899
drosophila_melanogaster	Mipp2	FBGN0026060
drosophila_melanogaster	Mipp1	FBGN0026061

Protein

Protein identifiers

Multiple inositol polyphosphate phosphatase 1 — Q9UNW1 (reviewed: Q9UNW1)

Alternative names: 2,3-bisphosphoglycerate 3-phosphatase

All UniProt accessions (1): Q9UNW1

UniProt curated annotations — full annotation on UniProt →

Function. 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. This regulates the availability of these various small molecule second messengers and metal chelators which control many aspects of cell physiology. Has a weak in vitro activity towards 1D-myo-inositol 1,4,5-trisphosphate which is unlikely to be physiologically relevant. By regulating intracellular inositol polyphosphates pools, which act as metal chelators, it may control the availability of intracellular calcium and iron, which are important for proper neuronal development and homeostasis. May have a dual substrate specificity, and function as a 2,3-bisphosphoglycerate 3-phosphatase hydrolyzing 2,3-bisphosphoglycerate to 2-phosphoglycerate. 2,3-bisphosphoglycerate (BPG) is formed as part of the Rapoport-Luebering glycolytic bypass and is a regulator of systemic oxygen homeostasis as the major allosteric effector of hemoglobin.

Subcellular location. Endoplasmic reticulum lumen. Secreted. Cell membrane.

Tissue specificity. Widely expressed with highest levels in kidney, liver, cerebellum and placenta.

Post-translational modifications. N-glycosylated.

Disease relevance. Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470] A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. Disease susceptibility is associated with variants affecting the gene represented in this entry. Pontocerebellar hypoplasia 16 (PCH16) [MIM:619527] A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH16 is an autosomal recessive, severe form characterized by hypotonia and severe global developmental delay apparent from early infancy. Other features may include stereotypic movements, spasticity, and progressive microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the histidine acid phosphatase family. MINPP1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UNW1-1	1	yes
Q9UNW1-2	2
Q9UNW1-3	3
Q9UNW1-4	4

RefSeq proteins (3): NP_001171588, NP_001171589, NP_004888* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000560	His_Pase_clade-2	Family
IPR016274	Histidine_acid_Pase_euk	Family
IPR029033	His_PPase_superfam	Homologous_superfamily

Pfam: PF00328

Enzyme classification (BRENDA):

• EC 3.1.3.62 — multiple inositol-polyphosphate phosphatase (BRENDA: 11 organisms, 28 substrates, 31 inhibitors, 14 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MYO-INOSITOL 1,3,4,5-TETRAKISPHOSPHATE	0.0001–0.0016	3
INOSITOL HEXAKISPHOSPHATE	—	3
MYO-INOSITOL HEXAKISPHOSPHATE	0.06–0.14	3
2,3-BISPHOSPHOGLYCERATE	0.61	1
INOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE	—	1
SCYLLO-INOSITOL HEXAKISPHOSPHATE	1.74	1

Catalyzed reactions (Rhea), 12 shown:

• 1D-myo-inositol hexakisphosphate + H2O = 1D-myo-inositol 1,2,4,5,6-pentakisphosphate + phosphate (RHEA:16989)
• 1D-myo-inositol hexakisphosphate + H2O = 1D-myo-inositol 1,2,3,5,6-pentakisphosphate + phosphate (RHEA:20960)
• (2R)-2,3-bisphosphoglycerate + H2O = (2R)-2-phosphoglycerate + phosphate (RHEA:27381)
• 1D-myo-inositol 1,2,3,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,2,3,6-tetrakisphosphate + phosphate (RHEA:77111)
• 1D-myo-inositol 1,2,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,2,5,6-tetrakisphosphate + phosphate (RHEA:77115)
• 1D-myo-inositol 1,2,5,6-tetrakisphosphate + H2O = 1D-myo-inositol 1,2,6-trisphosphate + phosphate (RHEA:77119)
• 1D-myo-inositol 1,2,3,6-tetrakisphosphate + H2O = 1D-myo-inositol 1,2,3-trisphosphate + phosphate (RHEA:77123)
• 1D-myo-inositol 1,2,3-trisphosphate + H2O = 1D-myo-inositol 2,3-bisphosphate + phosphate (RHEA:77127)
• 1D-myo-inositol 1,2,6-trisphosphate + H2O = 1D-myo-inositol 1,2-bisphosphate + phosphate (RHEA:77131)
• 1D-myo-inositol 1,2-bisphosphate + H2O = 1D-myo-inositol 2-phosphate + phosphate (RHEA:77135)
• 1D-myo-inositol 2,3-bisphosphate + H2O = 1D-myo-inositol 2-phosphate + phosphate (RHEA:77139)
• 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,4,5,6-tetrakisphosphate + phosphate (RHEA:77143)

UniProt features (27 total): sequence variant 9, splice variant 5, sequence conflict 5, mutagenesis site 2, glycosylation site 2, signal peptide 1, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNW1-F1	90.42	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 89

Glycosylation sites (2): 242, 481

Mutagenesis-validated functional residues (2):

Position	Phenotype
89	strong reduction of 2,3-bisphosphoglycerate 3-phosphatase activity.
370	greatly diminishes phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855231	Synthesis of IPs in the ER lumen
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 321 (showing top): GNF2_PRDX2, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GNF2_ANK1, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_3, FOSTER_TOLERANT_MACROPHAGE_UP, KOYAMA_SEMA3B_TARGETS_UP, GOBP_BONE_MINERALIZATION, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_ONLY_DN, GNF2_SPTA1

GO Biological Process (4): ossification (GO:0001503), intracellular monoatomic cation homeostasis (GO:0030003), bone mineralization (GO:0030282), inositol phosphate metabolic process (GO:0043647)

GO Molecular Function (16): acid phosphatase activity (GO:0003993), inositol hexakisphosphate phosphatase activity (GO:0004446), inositol hexakisphosphate 4-phosphatase activity (GO:0008707), inositol hexakisphosphate 3-phosphatase activity (GO:0016158), inositol bisphosphate phosphatase activity (GO:0016312), inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity (GO:0030351), inositol-1,4,5,6-tetrakisphosphate 6-phosphatase activity (GO:0030352), bisphosphoglycerate 3-phosphatase activity (GO:0034417), inositol trisphosphate phosphatase activity (GO:0046030), inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity (GO:0051717), inositol phosphate phosphatase activity (GO:0052745), inositol pentakisphosphate phosphatase activity (GO:0052827), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), obsolete inositol hexakisphosphate 2-phosphatase activity (GO:0052826)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Inositol phosphate metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inositol phosphate phosphatase activity	4
phosphatase activity	3
inositol hexakisphosphate phosphatase activity	2
inositol tetrakisphosphate phosphatase activity	2
cellular anatomical structure	2
multicellular organismal process	1
intracellular monoatomic ion homeostasis	1
monoatomic cation homeostasis	1
ossification	1
biomineral tissue development	1
organophosphate metabolic process	1
polyol metabolic process	1
inositol pentakisphosphate phosphatase activity	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

722 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MINPP1	IPP	Q9Y573	881
MINPP1	CDHR1	Q96JP9	743
MINPP1	IPPK	Q9H8X2	689
MINPP1	PTEN	P60484	627
MINPP1	BMPR1A	P36894	577
MINPP1	IPMK	Q8NFU5	574
MINPP1	ITPK1	Q13572	512
MINPP1	IP6K3	Q96PC2	498
MINPP1	IP6K1	Q92551	442
MINPP1	INPP1	P49441	436
MINPP1	IP6K2	Q9UHH9	432
MINPP1	ISYNA1	Q9NPH2	383
MINPP1	HAAO	P46952	382
MINPP1	PCBD1	P61457	361
MINPP1	KLHL15	Q96M94	350

IntAct

26 interactions, top by confidence:

A	B	Type	Score
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
UBQLN2	MINPP1	psi-mi:“MI:0915”(physical association)	0.560
LYPD6	PLXNB2	psi-mi:“MI:0914”(association)	0.530
IL27RA	B4GALT5	psi-mi:“MI:0914”(association)	0.530
SPINK4	PLXNA2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350
EFNA5	NBAS	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
CD274	TNPO2	psi-mi:“MI:0914”(association)	0.350
FOXRED1	CLPX	psi-mi:“MI:0914”(association)	0.350
GIMAP1	PRR5	psi-mi:“MI:0914”(association)	0.350
MINPP1	MGAT2	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
	MYO1C	psi-mi:“MI:0914”(association)	0.350
TCTN1	TOR1A	psi-mi:“MI:2364”(proximity)	0.270
TCTN1	PLOD2	psi-mi:“MI:2364”(proximity)	0.270
MINPP1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (73): MINPP1 (Affinity Capture-MS), MINPP1 (Affinity Capture-MS), MINPP1 (Affinity Capture-MS), MINPP1 (Affinity Capture-MS), MINPP1 (Affinity Capture-MS), MINPP1 (Two-hybrid), MINPP1 (Co-fractionation), MINPP1 (Proximity Label-MS), VWA1 (Affinity Capture-MS), C1orf87 (Affinity Capture-MS), HNRNPLL (Affinity Capture-MS), MRS2 (Affinity Capture-MS), MINPP1 (Affinity Capture-MS), MINPP1 (Affinity Capture-MS), GDAP1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5C7, A6H7A0, B0BMW8, B0CM95, B0KWE9, B1MTH4, B2KI79, O43688, O62772, O75147, P0CK96, P35438, P35439, P52875, P57791, Q05586, Q28D01, Q2KJ29, Q3KNV8, Q3SZQ2, Q3UHH2, Q4L208, Q4V899, Q5R1P0, Q5R890, Q5SP67, Q5ZJ75, Q7TPB4, Q86YN1, Q8BTQ0, Q8C6G8, Q8C811, Q8R4D1, Q8VDI9, Q8VE98, Q90812, Q9BWV1, Q9D9E0, Q9H6U8, Q9H7D7

Diamond homologs: F1NPQ2, O35217, Q5R890, Q9UNW1, Q9VV72, Q9Z2L6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

74 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	6
Uncertain significance	46
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1285620	NM_004897.5(MINPP1):c.300del (p.Lys101fs)	Pathogenic
1300179	NM_004897.5(MINPP1):c.1027_1028del (p.Ile343fs)	Pathogenic
3377176	NM_004897.5(MINPP1):c.903G>A (p.Trp301Ter)	Pathogenic
5021	NM_004897.5(MINPP1):c.122C>T (p.Ser41Leu)	Pathogenic
5022	NM_004897.5(MINPP1):c.809A>G (p.Gln270Arg)	Pathogenic
1285619	NM_004897.5(MINPP1):c.157T>G (p.Tyr53Asp)	Likely pathogenic
1325784	NM_004897.5(MINPP1):c.851C>A (p.Ala284Asp)	Likely pathogenic
2628617	NM_004897.5(MINPP1):c.687dup (p.Asp230Ter)	Likely pathogenic
3064384	NM_004897.5(MINPP1):c.940G>T (p.Glu314Ter)	Likely pathogenic
3775954	NM_004897.5(MINPP1):c.1097_1098del (p.Leu366fs)	Likely pathogenic
4082279	NM_004897.5(MINPP1):c.422G>A (p.Trp141Ter)	Likely pathogenic

SpliceAI

1148 predictions. Top by Δscore:

Variant	Effect	Δscore
10:87508331:TTCA:T	acceptor_loss	1.0000
10:87508332:TCA:T	acceptor_loss	1.0000
10:87508334:A:AG	acceptor_gain	1.0000
10:87508335:G:GA	acceptor_gain	1.0000
10:87508335:GA:G	acceptor_gain	1.0000
10:87508335:GAT:G	acceptor_gain	1.0000
10:87508335:GATA:G	acceptor_gain	1.0000
10:87508335:GATAT:G	acceptor_gain	1.0000
10:87508511:GCC:G	donor_gain	1.0000
10:87508529:TGCAG:T	donor_loss	1.0000
10:87508530:GCAGG:G	donor_loss	1.0000
10:87508531:CAG:C	donor_loss	1.0000
10:87508532:AG:A	donor_loss	1.0000
10:87508533:G:GC	donor_loss	1.0000
10:87508534:GTA:G	donor_loss	1.0000
10:87508535:T:G	donor_loss	1.0000
10:87511336:GCTTC:G	donor_gain	1.0000
10:87513218:AAAGG:A	donor_loss	1.0000
10:87513219:AAGGT:A	donor_loss	1.0000
10:87513220:AGGTA:A	donor_loss	1.0000
10:87513222:G:GA	donor_loss	1.0000
10:87513223:TAA:T	donor_loss	1.0000
10:87521166:AAAGG:A	donor_loss	1.0000
10:87521168:AGGTA:A	donor_loss	1.0000
10:87521170:G:GA	donor_loss	1.0000
10:87521171:T:A	donor_loss	1.0000
10:87546746:C:G	donor_gain	1.0000
10:87505548:CGCAG:C	donor_loss	0.9900
10:87505549:GCAGG:G	donor_loss	0.9900
10:87505550:CAG:C	donor_loss	0.9900

AlphaMissense

3171 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:87521058:T:C	L319P	0.999
10:87505459:A:C	S182R	0.998
10:87505461:T:A	S182R	0.998
10:87505461:T:G	S182R	0.998
10:87505483:A:C	S190R	0.998
10:87505485:C:A	S190R	0.998
10:87505485:C:G	S190R	0.998
10:87505476:C:G	C187W	0.997
10:87521108:A:C	S336R	0.997
10:87521110:C:A	S336R	0.997
10:87521110:C:G	S336R	0.997
10:87505177:C:A	R88S	0.996
10:87552120:G:A	G369D	0.996
10:87552258:T:C	L415P	0.996
10:87505182:C:A	H89Q	0.995
10:87505182:C:G	H89Q	0.995
10:87505475:G:A	C187Y	0.995
10:87552333:A:T	E440V	0.995
10:87505180:C:G	H89D	0.994
10:87505178:G:C	R88P	0.993
10:87505184:G:T	G90V	0.993
10:87505484:G:T	S190I	0.993
10:87508383:T:C	F229L	0.993
10:87508385:T:A	F229L	0.993
10:87508385:T:G	F229L	0.993
10:87505177:C:G	R88G	0.992
10:87505363:G:A	G150R	0.992
10:87505363:G:C	G150R	0.992
10:87505460:G:T	S182I	0.992
10:87508393:G:A	C232Y	0.992

dbSNP variants (sampled 300 via entrez): RS1000014698 (10:87517281 T>G), RS1000238775 (10:87507408 C>G,T), RS1000362068 (10:87549726 G>A), RS1000417624 (10:87526497 C>T), RS1000430086 (10:87544870 A>G), RS1000725342 (10:87536740 C>A), RS1000801856 (10:87528085 A>G), RS1000830824 (10:87543622 T>G), RS1000968225 (10:87515676 C>G,T), RS1001069593 (10:87522716 T>C), RS1001191944 (10:87516858 T>G), RS1001240521 (10:87523509 C>A,G), RS1001293087 (10:87523183 T>A), RS1001404820 (10:87503908 A>G), RS1001451908 (10:87531393 C>A,T)

Disease associations

OMIM: gene MIM:605391 | disease phenotypes: MIM:619527, MIM:607596, MIM:188470

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia, type 16	Strong	Autosomal recessive
pontocerebellar hypoplasia type 7	Supportive	Autosomal recessive
thyroid cancer, nonmedullary, 2	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pontocerebellar hypoplasia	Definitive	AR

Mondo (4): pontocerebellar hypoplasia, type 16 (MONDO:0030438), pontocerebellar hypoplasia (MONDO:0020135), thyroid cancer, nonmedullary, 2 (MONDO:0008566), pontocerebellar hypoplasia type 7 (MONDO:0013993)

Orphanet (1): Non-syndromic pontocerebellar hypoplasia (Orphanet:98523)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000133	Gonadal dysgenesis
HP:0000151	Aplasia of the uterus
HP:0000215	Thick upper lip vermilion
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000853	Goiter
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001321	Cerebellar hypoplasia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000632_1	Longevity	7.000000e-07
GCST005024_14	Pursuit maintenance gain	3.000000e-06
GCST006106_3	Forehead morphology	2.000000e-06
GCST006585_103	Blood protein levels	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C580383	Pontocerebellar Hypoplasia (supp.)
C572845	Thyroid cancer, follicular (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation	2
sodium arsenite	affects methylation, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Valproic Acid	decreases methylation, increases expression, affects expression	2
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Rifampin	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04544111	PHASE2	ACTIVE_NOT_RECRUITING	PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer
NCT04462471	PHASE1	COMPLETED	Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers
NCT05796960	Not specified	UNKNOWN	European Multicenter Study on Surgical Management of Advanced Thyroid Cancer
NCT06730321	Not specified	RECRUITING	Surgical Competency for Robot-Assisted Thyroidectomy: Construction and Validation of a Robotic Thyroidectomy Assessment Score (RTAS)
NCT07122557	Not specified	NOT_YET_RECRUITING	Real World Effectiveness of Bictegravir/Emtricitabine/Tenofovir Alafenamide(BIC/FTC/TAF) in PLWH in Precarity Settings in France -IMEA073