ITPKC

protein-coding

inositol-trisphosphate 3-kinase C

Gene summary

This gene encodes a member of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase family of enzymes that catalyze the phosphorylation of inositol 1,4,5-trisphosphate to 1,3,4,5-tetrakisphosphate. The encoded protein is localized to the nucleus and cytoplasm and has both nuclear import and nuclear export activity. Single nucleotide polymorphisms in this gene are associated with Kawasaki disease.[provided by RefSeq, Sep 2009]

MANE transcript

NM_025194.3

Inheritance

—

ClinVar variants

U:119B:11

Top phenotype

ITPKC-related disorder

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr19:40,717,112-40,740,860

External References & Databases

Ensembl (ENSG00000086544)

Transcript & Mutation Effects

hg38 • Region Span ~23.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITPKC variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 115

ITPKC-related disorderTotal: 8

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025194.3. 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			3 clinvar	4 clinvar		7
missense			111 clinvar	7 clinvar		118
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	119	11	0	130

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025194.3	RefSeq	NP_079470.1	7	MANE Select
ENST00000263370.3	Ensembl	ENSP00000263370.1	7	MANE Select
NM_001411098.1	RefSeq	NP_001398027.1	6	Standard
ENST00000597003.1	Ensembl	ENSP00000472655.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Integrated Breast Cancer Pathway
D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis

Biological Process

phosphorylation
inositol phosphate biosynthetic process
inositol phosphate metabolic process

Molecular Function

calmodulin binding
ATP binding
inositol-1,4,5-trisphosphate 3-kinase activity

Cellular Component

cytosol
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263370
Coding exons: 7
Length: 23758
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125747
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.532	343	372	0.922	0.0000203	4418
Missense (PolyPhen)		80	125.35	0.63823		1468
Synonymous	0.768	139	151	0.921	0.00000856	1390
Loss of Function	3.66	7	27.8	0.252	0.00000137	302

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000067	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Can phosphorylate inositol 2,4,5-triphosphate to inositol 2,4,5,6-tetraphosphate. {ECO:0000250}.;

Recessive Scores

pRec: 0.0933

Intolerance Scores

LoFtool: 0.176
RVIS EVS: -0.51
RVIS percentile EVS: 21.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.648

Gene Damage Prediction

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