INPP4A

Summary

INPP4A (inositol polyphosphate-4-phosphatase type I A, HGNC:6074) is a protein-coding gene on chromosome 2q11.2, encoding Inositol polyphosphate-4-phosphatase type I A (Q96PE3). Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).

This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 3631 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 145 total — 8 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 131
• MANE Select transcript: NM_001134225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6074
Approved symbol	INPP4A
Name	inositol polyphosphate-4-phosphatase type I A
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000040933
Ensembl biotype	protein_coding
OMIM	600916
Entrez	3631

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 33 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000409016, ENST00000409463, ENST00000409540, ENST00000409851, ENST00000463367, ENST00000467042, ENST00000468638, ENST00000498026, ENST00000523221, ENST00000706935, ENST00000715853, ENST00000715854, ENST00000715897, ENST00000715898, ENST00000715899, ENST00000715900, ENST00000715901, ENST00000715902, ENST00000851855, ENST00000851856, ENST00000851857, ENST00000851858, ENST00000851859, ENST00000851860, ENST00000920516, ENST00000920517, ENST00000920518, ENST00000920519, ENST00000920520, ENST00000920521, ENST00000941124, ENST00000941125, ENST00000941126, ENST00000941127, ENST00000941128, ENST00000941129, ENST00000941130, ENST00000941131

RefSeq mRNA: 10 — MANE Select: NM_001134225 NM_001134224, NM_001134225, NM_001351424, NM_001351425, NM_001351426, NM_001351427, NM_001351428, NM_001351429, NM_001566, NM_004027

CCDS: CCDS46369, CCDS46370, CCDS46371, CCDS46372

Canonical transcript exons

ENST00000409851 — 25 exons

Exon	Start	End
ENSE00000487373	98520687	98520731
ENSE00000487374	98533377	98533495
ENSE00000487377	98537863	98537974
ENSE00000487378	98538891	98538981
ENSE00000487380	98543877	98544007
ENSE00000487388	98564640	98564763
ENSE00000771550	98546586	98546694
ENSE00000771551	98552786	98552969
ENSE00000771558	98565640	98565766
ENSE00000804199	98535729	98535845
ENSE00000804200	98536129	98536208
ENSE00000804203	98539528	98539675
ENSE00000804205	98545969	98546073
ENSE00000804208	98554271	98554489
ENSE00000804210	98559463	98559495
ENSE00000804211	98563465	98563637
ENSE00000804214	98566029	98566169
ENSE00001072360	98555553	98555808
ENSE00001578782	98518964	98519025
ENSE00002115759	98587476	98594392
ENSE00003504996	98568571	98568668
ENSE00003513643	98576989	98577143
ENSE00003522059	98572815	98572927
ENSE00003692344	98519946	98520154
ENSE00003900692	98444858	98445085

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7073 / max 684.2413, expressed in 1801 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21547	20.7073	1801

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.80	gold quality
endothelial cell	CL:0000115	97.81	gold quality
tibia	UBERON:0000979	97.15	gold quality
entorhinal cortex	UBERON:0002728	96.82	gold quality
postcentral gyrus	UBERON:0002581	96.60	gold quality
parietal lobe	UBERON:0001872	96.13	gold quality
superior frontal gyrus	UBERON:0002661	95.88	gold quality
buccal mucosa cell	CL:0002336	95.67	gold quality
middle temporal gyrus	UBERON:0002771	95.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.33	gold quality
visceral pleura	UBERON:0002401	94.76	gold quality
parietal pleura	UBERON:0002400	94.29	gold quality
adult organism	UBERON:0007023	93.94	gold quality
superficial temporal artery	UBERON:0001614	93.75	gold quality
cauda epididymis	UBERON:0004360	93.25	gold quality
pleura	UBERON:0000977	93.08	gold quality
trabecular bone tissue	UBERON:0002483	92.88	gold quality
substantia nigra pars compacta	UBERON:0001965	92.87	gold quality
pons	UBERON:0000988	92.68	gold quality
epithelium of nasopharynx	UBERON:0001951	92.65	gold quality
blood	UBERON:0000178	92.56	gold quality
cortical plate	UBERON:0005343	92.49	gold quality
primary visual cortex	UBERON:0002436	92.33	gold quality
lateral globus pallidus	UBERON:0002476	92.12	gold quality
occipital lobe	UBERON:0002021	92.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.97	gold quality
germinal epithelium of ovary	UBERON:0001304	91.79	gold quality
mucosa of stomach	UBERON:0001199	91.72	gold quality
superior vestibular nucleus	UBERON:0007227	91.70	gold quality
caput epididymis	UBERON:0004358	90.88	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	35.42
E-CURD-122	yes	12.48
E-ANND-3	yes	4.83

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 10)

• in quiescent cells, the 4-phosphatase colocalized with early and recycling endosomes (PMID:15716355)
• The +110832A/G (Thr/Ala) variant of INPP4A was significantly associated with asthma in an Indian population. (PMID:18187694)
• INPP4A represents the first signalling protein with a function in neurons to suppress excitotoxic cell death (PMID:20463662)
• Data adds a new etiology to the spectrum of hindbrain malformations in human, and when presented with myoclonic epilepsy may lead to the clinical suspicion of INPP4A defect. (PMID:25338135)
• INPP4A could possibly serve as a candidate gene for alterations associated with asbestos exposure. (PMID:26463840)
• INPP4A is secreted by airway epithelial cells and extracellular INPP4A critically inhibits airway inflammation and remodeling. (PMID:30335467)
• Low INPP4A expression is associated with cell proliferation, migration, and invasion in colorectal cancer. (PMID:31524145)
• Whole exome sequencing identified a novel nonsense INPP4A mutation in a family with intellectual disability. (PMID:31978615)
• miR-935 Inhibits Oral Squamous Cell Carcinoma and Targets Inositol Polyphosphate-4-phosphatase Type IA (INPP4A). (PMID:33109548)
• Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps. (PMID:38363325)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	inpp4aa	ENSDARG00000063352
danio_rerio	inpp4ab	ENSDARG00000070995
mus_musculus	Inpp4a	ENSMUSG00000026113
rattus_norvegicus	Inpp4a	ENSRNOG00000017660

Paralogs (1): INPP4B (ENSG00000109452)

Protein

Protein identifiers

Inositol polyphosphate-4-phosphatase type I A — Q96PE3 (reviewed: Q96PE3)

Alternative names: Inositol polyphosphate 4-phosphatase type I, Type I inositol 3,4-bisphosphate 4-phosphatase

All UniProt accessions (3): A0A9L9PY55, B8ZZB2, Q96PE3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). Also catalyzes inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. May protect neurons from excitotoxic cell death by regulating the synaptic localization of cell surface N-methyl-D-aspartate-type glutamate receptors (NMDARs) and NMDAR-mediated excitatory postsynaptic current. Displays no 4-phosphatase activity for PtdIns(3,4)P2, Ins(3,4)P2, or Ins(1,3,4)P3.

Subunit / interactions. Interacts with INPP5F.

Subcellular location. Early endosome membrane. Recycling endosome membrane. Cell membrane. Nucleus. Cytoplasm. Postsynaptic density.

Tissue specificity. Isoform 1 is expressed in the platelets, MEG-01 megakaryocytes and Jurkat T-cells. Isoform 2 is expressed in the brain.

Pathway. Signal transduction; phosphatidylinositol signaling pathway.

Miscellaneous. Inactive.

Similarity. Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96PE3-1	1, Alpha-3	yes
Q96PE3-2	2, Alpha-1
Q96PE3-3	3
Q96PE3-4	4, Beta

RefSeq proteins (10): NP_001127696, NP_001127697, NP_001338353, NP_001338354, NP_001338355, NP_001338356, NP_001338357, NP_001338358, NP_001557, NP_004018 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR039034	INPP4	Family

Enzyme classification (BRENDA):

• EC 3.1.3.66 — phosphatidylinositol-3,4-bisphosphate 4-phosphatase (BRENDA: 4 organisms, 9 substrates, 7 inhibitors, 4 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MYO-INOSITOL 1,3,4-TRISPHOSPHATE	0.034–0.046	2
D-MYO-INOSITOL 3,4-BISPHOSPHATE	0.028–0.039	2

Catalyzed reactions (Rhea), 3 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + phosphate (RHEA:17193)
• 1D-myo-inositol 3,4-bisphosphate + H2O = 1D-myo-inositol 3-phosphate + phosphate (RHEA:43388)
• 1D-myo-inositol 1,3,4-trisphosphate + H2O = 1D-myo-inositol 1,3-bisphosphate + phosphate (RHEA:43392)

UniProt features (12 total): splice variant 3, mutagenesis site 2, modified residue 2, chain 1, domain 1, sequence conflict 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PE3-F1	80.39	0.58

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): 895 (phosphocysteine intermediate)

Post-translational modifications (2): 355, 487

Mutagenesis-validated functional residues (2):

Position	Phenotype
895	does not rescue the wortmannin-induced dilation of endosomes due to accumulation of (ptdins(3,4)p2).
731	complete loss of lipid phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1660516	Synthesis of PIPs at the early endosome membrane
R-HSA-1855183	Synthesis of IP2, IP, and Ins in the cytosol
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 254 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_3_PHOSPHATE_BIOSYNTHETIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, SREBP1_02, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, CEBP_Q2, OCT1_06

GO Biological Process (6): phosphatidylinositol biosynthetic process (GO:0006661), signal transduction (GO:0007165), inositol phosphate metabolic process (GO:0043647), lipid metabolic process (GO:0006629), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), small molecule metabolic process (GO:0044281)

GO Molecular Function (7): phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity (GO:0016316), inositol-1,3,4-trisphosphate 4-phosphatase activity (GO:0017161), inositol-3,4-bisphosphate 4-phosphatase activity (GO:0052828), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788), phosphatase activity (GO:0016791)

GO Cellular Component (13): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), early endosome membrane (GO:0031901), nuclear membrane (GO:0031965), recycling endosome membrane (GO:0055038), endosome (GO:0005768), membrane (GO:0016020), organelle (GO:0043226), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
PI Metabolism	2
Metabolism	2
Inositol phosphate metabolism	1
Phospholipid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
endosome membrane	2
biosynthetic process	1
phosphatidylinositol metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
organophosphate metabolic process	1
polyol metabolic process	1
primary metabolic process	1
phosphatidylinositol phosphate biosynthetic process	1
metabolic process	1
phosphatidylinositol phosphate 4-phosphatase activity	1
phosphatidylinositol-3-phosphate biosynthetic process	1
phosphatidylinositol-3,4-bisphosphate phosphatase activity	1
inositol trisphosphate phosphatase activity	1
inositol bisphosphate phosphatase activity	1
binding	1
catalytic activity	1
hydrolase activity	1
phosphoric ester hydrolase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
early endosome	1
nucleus	1
nuclear envelope	1
organelle membrane	1
recycling endosome	1
endomembrane system	1
cytoplasmic vesicle	1
cell junction	1

Protein interactions and networks

STRING

772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INPP4A	RAB5A	P20339	848
INPP4A	INPPL1	O15357	631
INPP4A	MCF2	P10911	624
INPP4A	PLEK	P08567	617
INPP4A	INPP5J	Q15735	612
INPP4A	ARHGEF1	Q92888	592
INPP4A	OCRL	Q01968	584
INPP4A	INPP5B	P32019	550
INPP4A	WDR18	Q9BV38	535
INPP4A	SYNJ1	O43426	532
INPP4A	PTEN	P60484	490
INPP4A	INPP5K	Q9BT40	490
INPP4A	PIK3R2	O00459	477
INPP4A	RABIF	P47224	476
INPP4A	PLEK2	Q9NYT0	464

IntAct

8 interactions, top by confidence:

A	B	Type	Score
INPP4A	HK3	psi-mi:“MI:0915”(physical association)	0.400
SMAD1	INPP4A	psi-mi:“MI:0915”(physical association)	0.370
NTAQ1	SBNO1	psi-mi:“MI:0914”(association)	0.350
NXT2	RGS8	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
DISC1	INPP4A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): INPP4A (Co-fractionation), INPP4A (Affinity Capture-MS), INPP4A (Affinity Capture-MS), INPP4A (Affinity Capture-MS), INPP4A (Affinity Capture-RNA), INPP4A (Affinity Capture-RNA), INPP4A (Affinity Capture-MS), INPP4A (Negative Genetic), INPP4A (Negative Genetic), INPP4A (Negative Genetic), INPP4A (Affinity Capture-MS), HK3 (Affinity Capture-MS), INPP4A (Affinity Capture-MS), INPP4A (Affinity Capture-MS), INPP4A (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A2AAE1, A2RV80, A4IFQ0, A6QQW8, F1Q8X5, O35382, P48553, P70398, Q08BT5, Q13769, Q2LD37, Q5F361, Q5R903, Q5RAQ5, Q5REX9, Q62824, Q68FX7, Q6DFZ1, Q6IC98, Q6NRC7, Q6P6Y1, Q6SP92, Q6ZWH5, Q7SXV1, Q7TSG1, Q7Z7G8, Q80TY5, Q8BHY8, Q8BKT7, Q8BQZ4, Q8CB44, Q8CIB5, Q8K3W0, Q8N960, Q8WN69, Q8WN70, Q91W96, Q92538

Diamond homologs: O15327, Q4R4D7, Q5RA60, Q62784, Q6P1Y8, Q96PE3, Q9EPW0, Q9QWG5, Q69ZK0, Q8TCU6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	2
Uncertain significance	89
Likely benign	8
Benign	7

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
4277308	INPP4A, GLN39TER	Pathogenic
4277310	NM_001134225.2(INPP4A):c.981del (p.Asp328fs)	Pathogenic
4277311	NM_001134225.2(INPP4A):c.2278C>T (p.Arg760Cys)	Pathogenic
4277312	NM_001134225.2(INPP4A):c.646C>T (p.Arg216Ter)	Pathogenic
4277313	NM_001134225.2(INPP4A):c.1567-81_1822+1434del	Pathogenic
4277314	INPP4A, 1-BP DEL, NT2726	Pathogenic
4277315	NM_001134225.2(INPP4A):c.106+1G>A	Pathogenic
801338	NM_001134225.2(INPP4A):c.115C>T (p.Gln39Ter)	Pathogenic
623236	NM_001134225.2(INPP4A):c.36C>T (p.Ala12=)	Likely pathogenic
804386	NM_001134225.2(INPP4A):c.352_353del (p.Ser118fs)	Likely pathogenic

SpliceAI

5633 predictions. Top by Δscore:

Variant	Effect	Δscore
2:98519021:GTCCA:G	donor_gain	1.0000
2:98519026:G:GG	donor_gain	1.0000
2:98533375:A:AG	acceptor_gain	1.0000
2:98533376:G:GA	acceptor_gain	1.0000
2:98535841:G:T	donor_gain	1.0000
2:98535851:G:GG	donor_gain	1.0000
2:98536128:GAT:G	acceptor_gain	1.0000
2:98537858:CACA:C	acceptor_loss	1.0000
2:98537860:CA:C	acceptor_loss	1.0000
2:98537861:A:AG	acceptor_gain	1.0000
2:98537861:A:C	acceptor_loss	1.0000
2:98537862:G:GA	acceptor_loss	1.0000
2:98537862:G:GG	acceptor_gain	1.0000
2:98537970:GGAGG:G	donor_gain	1.0000
2:98537971:GAGG:G	donor_gain	1.0000
2:98537971:GAGGG:G	donor_gain	1.0000
2:98537973:GG:G	donor_gain	1.0000
2:98537973:GGGTG:G	donor_loss	1.0000
2:98537974:GG:G	donor_gain	1.0000
2:98537975:G:C	donor_loss	1.0000
2:98537975:G:GG	donor_gain	1.0000
2:98538879:A:AG	acceptor_gain	1.0000
2:98538880:T:G	acceptor_gain	1.0000
2:98538881:A:AG	acceptor_gain	1.0000
2:98538882:C:G	acceptor_gain	1.0000
2:98538883:A:AG	acceptor_gain	1.0000
2:98538884:T:G	acceptor_gain	1.0000
2:98538889:AGAT:A	acceptor_gain	1.0000
2:98538890:GATG:G	acceptor_gain	1.0000
2:98539517:T:G	acceptor_gain	1.0000

AlphaMissense

6387 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:98533428:T:A	V68D	1.000
2:98554281:T:C	L458P	1.000
2:98577007:G:T	G889W	1.000
2:98577008:G:A	G889E	1.000
2:98577043:C:A	R901S	1.000
2:98577044:G:C	R901P	1.000
2:98577083:T:C	L914P	1.000
2:98520723:T:C	F48S	0.999
2:98535756:A:C	S100R	0.999
2:98535758:T:A	S100R	0.999
2:98535758:T:G	S100R	0.999
2:98535808:T:C	L117P	0.999
2:98537885:G:C	G164R	0.999
2:98537886:G:A	G164D	0.999
2:98539611:A:C	S252R	0.999
2:98539613:C:A	S252R	0.999
2:98539613:C:G	S252R	0.999
2:98543906:T:C	L283P	0.999
2:98543930:G:C	R291P	0.999
2:98546612:G:T	G361W	0.999
2:98552902:T:C	L432P	0.999
2:98552914:C:A	A436D	0.999
2:98552950:T:C	L448P	0.999
2:98554487:T:A	W527R	0.999
2:98554487:T:C	W527R	0.999
2:98555584:T:C	L538P	0.999
2:98563495:T:C	L634P	0.999
2:98563504:T:C	L637P	0.999
2:98564641:T:C	L682P	0.999
2:98564674:T:C	L693P	0.999

dbSNP variants (sampled 300 via entrez): RS1000024572 (2:98443769 T>C), RS1000057402 (2:98518050 C>T), RS1000058408 (2:98519866 G>C), RS1000121412 (2:98512148 T>C), RS1000146666 (2:98471118 T>C), RS1000175160 (2:98512411 C>T), RS1000180811 (2:98554842 G>A,T), RS1000202117 (2:98465628 G>C), RS1000214180 (2:98468775 A>G), RS1000217163 (2:98470070 C>A), RS1000239263 (2:98548138 A>C), RS1000270673 (2:98556070 A>C,G), RS1000278864 (2:98460840 C>T), RS1000292102 (2:98513584 A>T), RS1000304411 (2:98471608 A>G)

Disease associations

OMIM: gene MIM:600916 | disease phenotypes: MIM:621354, MIM:127550, MIM:169300

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (8): neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech (MONDO:0980699), dyskeratosis congenita, autosomal dominant 1 (MONDO:0007485), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), pathologic nystagmus (MONDO:0004843), pectus excavatum (MONDO:0008213), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (2): Dyskeratosis congenita (Orphanet:1775), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

131 total (30 of 131 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000164	Abnormality of the dentition
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000448	Prominent nose
HP:0000486	Strabismus
HP:0000512	Abnormal electroretinogram
HP:0000527	Long eyelashes
HP:0000565	Esotropia
HP:0000602	Ophthalmoplegia
HP:0000609	Optic nerve hypoplasia
HP:0000639	Nystagmus
HP:0000713	Agitation
HP:0000737	Irritability
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001007	Hirsutism
HP:0001159	Syndactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001715_15	Bipolar disorder with mood-incongruent psychosis	7.000000e-06

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D005660	Funnel Chest	C05.116.099.386; C05.660.386; C16.131.621.386
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
C565079	Dyskeratosis Congenita, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Inositol polyphosphate phosphatases

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
quercitrin	affects expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Lead	affects splicing	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Zinc	increases expression, affects cotreatment	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SS63	HAP1 INPP4A (-) 1	Cancer cell line	Male
CVCL_SS64	HAP1 INPP4A (-) 2	Cancer cell line	Male
CVCL_SS65	HAP1 INPP4A (-) 3	Cancer cell line	Male
CVCL_SS66	HAP1 INPP4A (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01486953	PHASE4	UNKNOWN	Pulmonary Mechanics During Minimally Invasive Repair of Pectus Excavatum
NCT02056301	PHASE4	TERMINATED	A Comparison Trial Between PCA and Epidural Analgesia for Pectus Excavatum Repair
NCT02169297	PHASE4	COMPLETED	Sub-Paraspinal Block in Nuss Patients. A Pilot Project
NCT02721017	PHASE4	COMPLETED	Cryoanalgesia vs. Epidural in the Nuss Procedure
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game