PIP5K1C

Chr 19ARAD

phosphatidylinositol-4-phosphate 5-kinase type 1 gamma

Also known as: LCCS3, NEDVIL, PIP5K-GAMMA, PIP5K1-gamma, PIP5Kgamma

NCBI Gene: 23396 ENSG00000186111 UniProt: O60331 OMIM: 606102

This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate, producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in endocytosis and cell migration. Mutations at this locus have been associated with lethal congenital contractural syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Sep 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

AR/ADLOEUF 0.312 OMIM phenotypes

Clinical Summary— PIP5K1C

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Gene-Disease Validity (ClinGen)

PIP5K1C-related neurodevelopmental disorder · ADStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 123 VUS of 289 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.977

Z-score 4.57

OE 0.15 (0.08–0.31)

Highly constrained

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

Missense Constraint?

2.29Z-score

OE missense 0.69 (0.63–0.76)

300 obs / 434.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.31)

0≤0.351.4

Missense OE?0.69 (0.63–0.76)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 5 / 33.6Missense obs/exp: 300 / 434.5Syn Z: -3.60

ClinVar Variant Classifications

289 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic1

VUS123

Likely Benign76

Benign61

Conflicting3

Pathogenic

Likely Pathogenic

123

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	4	0	0	6
Likely Pathogenic	1	0	0	0	1
VUS	5	113	5	0	123
Likely Benign	0	10	31	35	76
Benign	0	2	49	10	61
Conflicting	—				3
Total	8	129	85	45	270

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap PIP5K1C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →