ITPK1

Chr 14

inositol-tetrakisphosphate 1-kinase

Also known as: ITRPK1

NCBI Gene: 3705ENSG00000100605UniProt: Q13572OMIM: 601838

This enzyme phosphorylates and dephosphorylates various inositol polyphosphates, serving as the rate-limiting enzyme in the inositol hexakisphosphate pathway that is essential for neural tube development. Mutations cause neural tube defects in an autosomal recessive inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI = 0.99), indicating intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.24
Clinical Summary— ITPK1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 64 VUS of 100 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.994
Z-score 3.89
OE 0.05 (0.02–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.17Z-score
OE missense 0.80 (0.71–0.89)
214 obs / 268.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.02–0.24)
0≤0.351.4
Missense OE0.80 (0.71–0.89)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 1 / 19.6Missense obs/exp: 214 / 268.1Syn Z: -0.64

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS64
Likely Benign9
7
Pathogenic
1
Likely Pathogenic
64
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
59
5
0
64
Likely Benign
0
7
0
2
9
Benign
0
0
0
0
0
Total06613281

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ITPK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients