IMPA1

Summary

IMPA1 (inositol monophosphatase 1, HGNC:6050) is a protein-coding gene on chromosome 8q21.13, encoding Inositol monophosphatase 1 (P29218). Phosphatase involved in the dephosphorylation of myo-inositol monophosphates to generate myo-inositol.

This gene encodes an enzyme that dephosphorylates myo-inositol monophosphate to generate free myo-inositol, a precursor of phosphatidylinositol, and is therefore an important modulator of intracellular signal transduction via the production of the second messengers myoinositol 1,4,5-trisphosphate and diacylglycerol. This enzyme can also use myo-inositol-1,3-diphosphate, myo-inositol-1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2’-AMP as substrates. This enzyme shows magnesium-dependent phosphatase activity and is inhibited by therapeutic concentrations of lithium. Inhibition of inositol monophosphate hydroylosis and subsequent depletion of inositol for phosphatidylinositol synthesis may explain the anti-manic and anti-depressive effects of lithium administered to treat bipolar disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. A pseudogene of this gene is also present on chromosome 8q21.13.

Source: NCBI Gene 3612 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 59 (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 69 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6050
Approved symbol	IMPA1
Name	inositol monophosphatase 1
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000133731
Ensembl biotype	protein_coding
OMIM	602064
Entrez	3612

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 23 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000256108, ENST00000311489, ENST00000449740, ENST00000518188, ENST00000518202, ENST00000519816, ENST00000519964, ENST00000520065, ENST00000521360, ENST00000521979, ENST00000522997, ENST00000523710, ENST00000523942, ENST00000879909, ENST00000879910, ENST00000879911, ENST00000879912, ENST00000879913, ENST00000879914, ENST00000879915, ENST00000922705, ENST00000922706, ENST00000922707, ENST00000922708, ENST00000941267, ENST00000941268, ENST00000941269, ENST00000941270

RefSeq mRNA: 3 — MANE Select: NM_005536 NM_001144878, NM_001144879, NM_005536

CCDS: CCDS47883, CCDS47884, CCDS6231

Canonical transcript exons

ENST00000256108 — 9 exons

Exon	Start	End
ENSE00000909939	81676234	81676279
ENSE00000909941	81680650	81680783
ENSE00001747149	81656914	81659466
ENSE00002126032	81686252	81686325
ENSE00003494084	81660516	81660667
ENSE00003593695	81681498	81681584
ENSE00003663619	81679126	81679230
ENSE00003785068	81673841	81673949
ENSE00003789434	81670939	81671047

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8471 / max 514.0123, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93770	25.8412	1802
93769	0.0060	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.88	gold quality
oocyte	CL:0000023	97.63	gold quality
jejunal mucosa	UBERON:0000399	97.16	gold quality
endothelial cell	CL:0000115	96.67	gold quality
colonic mucosa	UBERON:0000317	96.64	gold quality
tibia	UBERON:0000979	96.61	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.58	gold quality
heart right ventricle	UBERON:0002080	96.33	gold quality
adult organism	UBERON:0007023	95.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.73	gold quality
choroid plexus epithelium	UBERON:0003911	95.69	gold quality
bronchial epithelial cell	CL:0002328	95.39	gold quality
pigmented layer of retina	UBERON:0001782	95.17	gold quality
middle temporal gyrus	UBERON:0002771	94.83	gold quality
esophagus squamous epithelium	UBERON:0006920	94.58	gold quality
nasal cavity epithelium	UBERON:0005384	94.42	gold quality
rectum	UBERON:0001052	94.23	gold quality
epithelium of nasopharynx	UBERON:0001951	94.21	gold quality
nasopharynx	UBERON:0001728	94.19	gold quality
palpebral conjunctiva	UBERON:0001812	94.15	gold quality
epithelium of bronchus	UBERON:0002031	94.08	gold quality
bronchus	UBERON:0002185	93.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.61	gold quality
ileal mucosa	UBERON:0000331	93.60	gold quality
postcentral gyrus	UBERON:0002581	93.41	gold quality
duodenum	UBERON:0002114	93.18	gold quality
germinal epithelium of ovary	UBERON:0001304	93.15	gold quality
myocardium	UBERON:0002349	93.11	gold quality
cranial nerve II	UBERON:0000941	92.88	gold quality
parietal pleura	UBERON:0002400	92.86	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting IMPA1, 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-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

• No association between polymorphisms and bipolar disorder (PMID:14699425)
• IMPA2 has a separate function in vivo from that of IMPA1 (PMID:17068342)
• The current study did not support a substantial role of the upregulation of IMPase in bipolar disorder, although the lithium-insensitivity trait seen in IMPA2 transgenic mice might represent some aspect relevant to the inositol depletion hypothesis. (PMID:20153384)
• Comparison of MmIMPase 1 and HsIMPase 1 revealed a core r.m.s. deviation of 0.516 A (PMID:23027737)
• The identification of a novel homozygous duplication of 5 bp in IMPA1, in a large consanguineous family with nine individuals with severe intellectual disability and disruptive behavior. (PMID:26416544)
• Multibody magnesium cofactor and myo-inositol substrate molecular recognition in the myo-inositol monophosphatase enzyme have been described. (PMID:27440438)
• the high-resolution X-ray structure of human IMPase in complex with L690,330 and manganese ions determined at 1.39 A resolution is reported. (PMID:30289407)
• Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG. The IMPA1 mutation in the cohort of the current study was associated with severe intellectual disability and disruptive behavior (PMID:30616629)
• Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (PMID:32839513)
• Inositol monophosphatase 1 (IMPA1) promotes triple-negative breast cancer progression through regulating mTOR pathway and EMT process. (PMID:35796646)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	impa1	ENSDARG00000003517
mus_musculus	Impa1	ENSMUSG00000027531
rattus_norvegicus	Impa1	ENSRNOG00000010482
drosophila_melanogaster	CG17026	FBGN0036550
drosophila_melanogaster	CG17029	FBGN0036551
drosophila_melanogaster	CG17028	FBGN0036552
drosophila_melanogaster	CG17027	FBGN0036553

Paralogs (4): BPNT2 (ENSG00000104331), IMPA2 (ENSG00000141401), INPP1 (ENSG00000151689), BPNT1 (ENSG00000162813)

Protein

Protein identifiers

Inositol monophosphatase 1 — P29218 (reviewed: P29218)

Alternative names: D-galactose 1-phosphate phosphatase, Inositol-1(or 4)-monophosphatase 1, Lithium-sensitive myo-inositol monophosphatase A1

All UniProt accessions (10): A0A140VJL8, E5RG13, E5RG94, P29218, E5RGY4, E5RHE9, E5RI82, E5RIF4, E5RIP7, H0YBL1

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatase involved in the dephosphorylation of myo-inositol monophosphates to generate myo-inositol. Is also able to dephosphorylate scyllo-inositol-phosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-1,3-diphosphate and scyllo-inositol-1,4-diphosphate. Also dephosphorylates in vitro other sugar-phosphates including D-galactose-1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate and 2’-AMP. Responsible for the provision of inositol required for synthesis of phosphatidylinositols and polyphosphoinositides, and involved in maintaining normal brain function. Has been implicated as the pharmacological target for lithium (Li(+)) action in brain, which is used to treat bipolar affective disorder. Is equally active with 1D-myo-inositol 1-phosphate, 1D-myo-inositol 3-phosphate and D-galactose 1-phosphate.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Disease relevance. Intellectual developmental disorder, autosomal recessive 59 (MRT59) [MIM:617323] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activity with myo-inositol monophosphates and D-galactose 1-phosphate is inhibited by Li(+), Ca(2+) and Mn(2+), but also by Mg(2+) at concentrations above 3 mM.

Pathway. Polyol metabolism; myo-inositol biosynthesis; myo-inositol from D-glucose 6-phosphate: step 2/2.

Similarity. Belongs to the inositol monophosphatase superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P29218-1	1	yes
P29218-2	2
P29218-3	3

RefSeq proteins (3): NP_001138350, NP_001138351, NP_005527* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000760	Inositol_monophosphatase-like	Family
IPR020550	Inositol_monophosphatase_CS	Conserved_site
IPR020552	Inositol_monoPase_Li-sen	Family
IPR020583	Inositol_monoP_metal-BS	Binding_site
IPR033942	IMPase	Family

Pfam: PF00459

Enzyme classification (BRENDA):

• EC 3.1.3.25 — inositol-phosphate phosphatase (BRENDA: 28 organisms, 184 substrates, 148 inhibitors, 96 Km, 55 kcat entries)

Substrate kinetics (BRENDA)

34 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MYO-INOSITOL 1-PHOSPHATE	0.06–1.02	14
DL-MYO-INOSITOL 1-PHOSPHATE	0.0034–1.67	12
L-MYO-INOSITOL 1-PHOSPHATE	0.061–13.2	8
MYO-INOSITOL 1-PHOSPHATE	0.064–66	8
GLYCEROL 2-PHOSPHATE	0.061–4.17	6
2’-AMP	0.083–1.58	5
4-NITROPHENYL PHOSPHATE	3.8–5	3
D-INOSITOL 1-PHOSPHATE	0.078–0.148	3
L-GLYCEROL 1-PHOSPHATE	0.382–0.87	3
3,5-DIDEOXY-D-MYO-INOSITOL 1-PHOSPHATE	0.051–0.16	2
3,5-DIDEOXY-L-MYO-INOSITOL 1-PHOSPHATE	0.1–4.9	2
3-DEOXY-D-MYO-INOSITOL 1-PHOSPHATE	0.047–0.23	2
3-DEOXY-L-MYO-INOSITOL 1-PHOSPHATE	0.2–2.3	2
D-MYO-INOSITOL 3-PHOSPHATE	0.061–1.7	2
INOSITOL 2-PHOSPHATE	0.286–0.733	2

Catalyzed reactions (Rhea), 12 shown:

• glycerol 2-phosphate + H2O = glycerol + phosphate (RHEA:13105)
• D-glucose 6-phosphate + H2O = D-glucose + phosphate (RHEA:16689)
• alpha-D-glucose 1-phosphate + H2O = D-glucose + phosphate (RHEA:19933)
• a myo-inositol phosphate + H2O = myo-inositol + phosphate (RHEA:24056)
• 1D-myo-inositol 1-phosphate + H2O = myo-inositol + phosphate (RHEA:27670)
• alpha-D-galactose 1-phosphate + H2O = D-galactose + phosphate (RHEA:29315)
• 1D-myo-inositol 4-phosphate + H2O = myo-inositol + phosphate (RHEA:30735)
• 1D-myo-inositol 3-phosphate + H2O = myo-inositol + phosphate (RHEA:30739)
• beta-D-fructose 1-phosphate + H2O = D-fructose + phosphate (RHEA:35603)
• adenosine 2’-phosphate + H2O = adenosine + phosphate (RHEA:37343)
• 1D-myo-inositol 2-phosphate + H2O = myo-inositol + phosphate (RHEA:44152)
• 1D-myo-inositol 5-phosphate + H2O = myo-inositol + phosphate (RHEA:44156)

UniProt features (48 total): strand 14, binding site 11, helix 10, mutagenesis site 4, turn 3, splice variant 2, chain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6GIU	X-RAY DIFFRACTION	1.39
6ZK0	X-RAY DIFFRACTION	1.47
4AS4	X-RAY DIFFRACTION	1.7
6GJ0	X-RAY DIFFRACTION	1.73
2HHM	X-RAY DIFFRACTION	2.1
1IMB	X-RAY DIFFRACTION	2.2
1IME	X-RAY DIFFRACTION	2.25
1IMA	X-RAY DIFFRACTION	2.3
1AWB	X-RAY DIFFRACTION	2.5
1IMF	X-RAY DIFFRACTION	2.5
1IMC	X-RAY DIFFRACTION	2.6
1IMD	X-RAY DIFFRACTION	2.6
7VCE	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29218-F1	96.23	0.92

Functional residue map

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

Ligand- & substrate-binding residues (11): 70; 220; 220; 70; 90; 90; 92–95; 92; 93; 194–196; 213

Post-translational modifications (1): 168

Mutagenesis-validated functional residues (4):

Position	Phenotype
36	50-fold reduction in activity.
93	loss of activity.
165	reduced enzyme activity with myo-inositol 1-phosphate.
213	strongly reduced affinity for myo-inositol 1-phosphate and strongly reduced enzyme activity with myo-inositol 1-phosphat

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855183	Synthesis of IP2, IP, and Ins in the cytosol
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 214 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MORF_RAGE, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, MORF_ATRX, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (6): inositol metabolic process (GO:0006020), inositol biosynthetic process (GO:0006021), phosphatidylinositol biosynthetic process (GO:0006661), phosphate-containing compound metabolic process (GO:0006796), signal transduction (GO:0007165), phosphatidylinositol phosphate biosynthetic process (GO:0046854)

GO Molecular Function (16): magnesium ion binding (GO:0000287), glucose-6-phosphatase activity (GO:0004346), glucose-1-phosphatase activity (GO:0008877), inositol monophosphate 1-phosphatase activity (GO:0008934), manganese ion binding (GO:0030145), lithium ion binding (GO:0031403), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), glycerol-2-phosphatase activity (GO:0047954), inositol monophosphate 3-phosphatase activity (GO:0052832), inositol monophosphate 4-phosphatase activity (GO:0052833), inositol monophosphate phosphatase activity (GO:0052834), fructose-1-phosphatase activity (GO:0103026), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

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 monophosphate phosphatase activity	3
phosphatase activity	2
cellular anatomical structure	2
polyol metabolic process	1
inositol metabolic process	1
polyol biosynthetic process	1
biosynthetic process	1
phosphatidylinositol metabolic process	1
metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
glycerophospholipid biosynthetic process	1
metal ion binding	1
sugar-terminal-phosphatase activity	1
sugar-phosphatase activity	1
transition metal ion binding	1
alkali metal ion binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
inositol phosphate phosphatase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMPA1	ISYNA1	Q9NPH2	743
IMPA1	IMPDH1	P20839	606
IMPA1	GSK3B	P49841	604
IMPA1	INPP1	P49441	583
IMPA1	SLC5A3	P53794	578
IMPA1	PHGDH	O43175	560
IMPA1	BPNT2	Q9NX62	537
IMPA1	IPMK	Q8NFU5	527
IMPA1	SFPQ	P23246	480
IMPA1	CDIPT	O14735	478
IMPA1	MRPL27	Q9P0M9	453
IMPA1	MIOX	Q9UGB7	451
IMPA1	ACTB	P02570	448
IMPA1	IMPA2	O14732	444
IMPA1	ZNF704	Q6ZNC4	441

IntAct

24 interactions, top by confidence:

A	B	Type	Score
IMPA1	IMPA1	psi-mi:“MI:0915”(physical association)	0.750
IMPA2	IMPA1	psi-mi:“MI:0915”(physical association)	0.680
IMPA1	IMPA2	psi-mi:“MI:0915”(physical association)	0.680
IMPA1	Impa1	psi-mi:“MI:0407”(direct interaction)	0.440
IMPA1	E6	psi-mi:“MI:0915”(physical association)	0.370
IMPA1	IMPA1	psi-mi:“MI:0915”(physical association)	0.370
ATG16L1		psi-mi:“MI:0914”(association)	0.350
IMPA1	METTL18	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
IL2RG	BBOX1	psi-mi:“MI:0914”(association)	0.350
RBPMS	CA2	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (59): IMPA1 (Two-hybrid), IMPA2 (Two-hybrid), IMPA1 (Two-hybrid), ARHGDIA (Co-fractionation), DUT (Co-fractionation), IMPA1 (Co-fractionation), IMPA1 (Co-fractionation), IMPA1 (Co-fractionation), IMPA1 (Co-fractionation), IMPA2 (Co-fractionation), ISCU (Co-fractionation), PHPT1 (Co-fractionation), SCPEP1 (Co-fractionation), TXN (Co-fractionation), UGDH (Co-fractionation)

ESM2 similar proteins: A0A0F6B4W4, A0QX86, A1URA6, A7HYA5, B0B944, B0BAS3, B0TAY4, B4ED80, B4F224, O14732, O49071, O55023, O77591, O84822, P0ADG4, P0ADG5, P0ADG6, P20456, P29218, P29219, P44332, P44333, P54926, P54927, P54928, P56160, P56947, P58537, P73833, P74158, P97697, Q19420, Q3KKM5, Q3SJR2, Q54U72, Q5R4X0, Q6FYQ7, Q87BG1, Q8CIN7, Q91UZ5

Diamond homologs: A0A0F6B4W4, A0QX86, B4ED80, O14732, O26957, O30298, O33832, O49071, O53907, O55023, O67791, O77591, P0ADG4, P0ADG5, P0ADG6, P11634, P20456, P25416, P29218, P29219, P38710, P44333, P46813, P54926, P54927, P54928, P55450, P57372, P58537, P65166, P74158, P95189, P97697, P9WKI8, P9WKI9, Q05533, Q19420, Q45499, Q54U72, Q5JH93

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	39
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
375412	NM_005536.4(IMPA1):c.489_493dup (p.Ser165fs)	Pathogenic
688202	GRCh37/hg19 8q21.13(chr8:82571433-82604029)x1	Pathogenic
1679268	NM_005536.4(IMPA1):c.817C>T (p.Arg273Ter)	Likely pathogenic

SpliceAI

1683 predictions. Top by Δscore:

Variant	Effect	Δscore
8:81673835:TCCTA:T	donor_loss	1.0000
8:81673836:CCTAC:C	donor_loss	1.0000
8:81673837:CTA:C	donor_loss	1.0000
8:81673838:TACC:T	donor_loss	1.0000
8:81673839:ACCTT:A	donor_loss	1.0000
8:81673840:C:T	donor_loss	1.0000
8:81673840:CCTT:C	donor_gain	1.0000
8:81673946:CTAT:C	acceptor_gain	1.0000
8:81673950:C:CC	acceptor_gain	1.0000
8:81679125:CCTAT:C	donor_gain	1.0000
8:81679226:TGAAA:T	acceptor_gain	1.0000
8:81679227:GAAA:G	acceptor_gain	1.0000
8:81679229:AA:A	acceptor_gain	1.0000
8:81679230:AC:A	acceptor_loss	1.0000
8:81679231:C:CC	acceptor_gain	1.0000
8:81679231:C:T	acceptor_loss	1.0000
8:81679232:T:G	acceptor_loss	1.0000
8:81680668:T:A	donor_gain	1.0000
8:81680780:CTAC:C	acceptor_gain	1.0000
8:81681490:G:C	donor_gain	1.0000
8:81659465:ACCT:A	acceptor_loss	0.9900
8:81659466:CCTAA:C	acceptor_loss	0.9900
8:81659468:T:G	acceptor_loss	0.9900
8:81660503:T:A	donor_gain	0.9900
8:81660510:TTTTA:T	donor_loss	0.9900
8:81660511:TTTA:T	donor_loss	0.9900
8:81660512:TTAC:T	donor_loss	0.9900
8:81660513:TACCT:T	donor_loss	0.9900
8:81660514:A:AT	donor_loss	0.9900
8:81660516:C:A	donor_loss	0.9900

AlphaMissense

1826 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:81660575:T:A	D220V	0.999
8:81679169:A:G	W87R	0.999
8:81679169:A:T	W87R	0.999
8:81679219:T:A	E70V	0.999
8:81660575:T:G	D220A	0.998
8:81660579:A:G	W219R	0.998
8:81660579:A:T	W219R	0.998
8:81679137:G:C	N97K	0.998
8:81679137:G:T	N97K	0.998
8:81679147:C:T	G94E	0.998
8:81679147:C:A	G94V	0.997
8:81679150:T:A	D93V	0.997
8:81679158:G:C	D90E	0.997
8:81679158:G:T	D90E	0.997
8:81679159:T:A	D90V	0.997
8:81679159:T:C	D90G	0.997
8:81679218:T:A	E70D	0.997
8:81679218:T:G	E70D	0.997
8:81680707:T:A	D47V	0.997
8:81660574:A:C	D220E	0.996
8:81660574:A:T	D220E	0.996
8:81660575:T:C	D220G	0.996
8:81660577:C:A	W219C	0.996
8:81660577:C:G	W219C	0.996
8:81660631:G:C	C201W	0.996
8:81660662:C:G	R191P	0.996
8:81679148:C:G	G94R	0.996
8:81679148:C:T	G94R	0.996
8:81679149:A:C	D93E	0.996
8:81679149:A:T	D93E	0.996

dbSNP variants (sampled 300 via entrez): RS1000010963 (8:81669749 T>C), RS1000039646 (8:81657399 T>A,C), RS1000118668 (8:81676614 T>C), RS1000257232 (8:81682036 G>A), RS1000315391 (8:81664146 T>C), RS1000328261 (8:81681762 T>C), RS1000457966 (8:81686970 A>C,T), RS1000836887 (8:81665877 G>A), RS1000863502 (8:81685333 T>C), RS1001023997 (8:81671352 G>C), RS1001109417 (8:81659206 T>A,C), RS1001125281 (8:81677842 T>C), RS1001494399 (8:81671078 A>T), RS1001580890 (8:81673216 C>T), RS1001583250 (8:81661641 G>A)

Disease associations

OMIM: gene MIM:602064 | disease phenotypes: MIM:617323

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 59	Moderate	Autosomal recessive

Mondo (1): intellectual disability, autosomal recessive 59 (MONDO:0015020)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000718	Aggressive behavior
HP:0001249	Intellectual disability
HP:0011999	Paranoia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001941_13	Ovarian cancer	6.000000e-09
GCST001941_17	Ovarian cancer	7.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1786 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Inositol monophosphatase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
Li+	Inhibition	3.5	pKi

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	4
sodium arsenite	increases expression, affects methylation, affects cotreatment, increases abundance	2
Air Pollutants	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol F	increases expression	1
bufotalin	increases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases expression, increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Coal	decreases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases expression, increases secretion	1
Doxorubicin	affects expression	1
Gold	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Polychlorinated Biphenyls	affects expression	1
Smoke	decreases expression, increases abundance	1
Testosterone	decreases expression	1
Dronabinol	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651629	Binding	Binding affinity to human IMPA1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2A1	HAP1 IMPA1 (-) 1	Cancer cell line	Male
CVCL_E2A2	HAP1 IMPA1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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