INPP4A

protein-coding

inositol polyphosphate-4-phosphatase type I A, the group of C2 domain containing

Gene summary

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. [provided by RefSeq, Aug 2008]

Previous symbols:

INPP4

MANE transcript

NM_001134225.2

Inheritance

ClinVar variants

P:8U:111B:22

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr2:98,444,854-98,594,392

External References & Databases

Ensembl (ENSG00000040933)

Transcript & Mutation Effects

hg38 • Region Span ~149.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INPP4A variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 108

not providedTotal: 23

Neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speechTotal: 6

HypotoniaTotal: 1

Pectus excavatumTotal: 1

NystagmusTotal: 1

Dyskeratosis congenita, autosomal dominant 1Total: 1

visual disturbanceTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001134225.2. 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		1 clinvar	2 clinvar	14 clinvar	6 clinvar	23
missense	1 clinvar		99 clinvar	2 clinvar		102
nonsense	2 clinvar		5 clinvar			7
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	2 clinvar		5 clinvar			7
Total	6	2	111	16	6	141

Highest pathogenic variant AF is 0.0000014888219

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 111 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001134225.2	RefSeq	NP_001127697.1	23	MANE Select
ENST00000409851.8	Ensembl	ENSP00000386777.4	23	MANE Select
NM_001134224.2	RefSeq	NP_001127696.1	24	Standard
NM_001351424.1	RefSeq	NP_001338353.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Inositol Phosphate Metabolism
Inositol Metabolism
Insulin Signaling

Biological Process

phosphatidylinositol biosynthetic process
signal transduction
dephosphorylation
phosphatidylinositol-3-phosphate biosynthetic process
inositol phosphate metabolic process

Molecular Function

protein binding
phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity
inositol-1,3,4-trisphosphate 4-phosphatase activity
phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity
inositol-3,4-bisphosphate 4-phosphatase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000074304
Coding exons: 24
Length: 149537
Individuals with no LoFs: 124658
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124667
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.35	357	585	0.611	0.0000368	6344
Missense (PolyPhen)		128	267.58	0.47836		2835
Synonymous	0.691	224	238	0.943	0.0000162	1886
Loss of Function	5.84	7	52.8	0.133	0.00000279	597

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00013	rare
Latino/Admixed American	0.000033	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0.000033	0.000033	rare
Other	0.00018	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4- trisphosphate and inositol 3,4-bisphosphate.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.270
RVIS EVS: -1.24
RVIS percentile EVS: 5.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.877

Gene Damage Prediction

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