PIP5KL1

Chr 9

phosphatidylinositol-4-phosphate 5-kinase like 1

Also known as: PIPKH

NCBI Gene: 138429 ENSG00000167103 UniProt: Q5T9C9 OMIM: 612865

The protein acts as a scaffold to localize and regulate type I PI(4)P 5-kinases to specific cellular compartments, where they generate PI(4,5)P2 for actin nucleation, signaling and scaffold protein recruitment. PIP5KL1 mutations cause disease through a predicted gain-of-function mechanism, though the specific associated disorder and inheritance pattern are not provided in the available data.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

PIP5KL1 is a phosphoinositide kinase-like protein that lacks intrinsic lipid kinase activity but associates with type I PIPKs (see PIP5K1A; MIM 603275) and may play a role in localization of PIPK activity (Chang et al., 2004 [PubMed 14701839]).[supplied by OMIM, Jun 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.73

OE 0.56 (0.34–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.79Z-score

OE missense 0.85 (0.76–0.96)

194 obs / 227.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.34–0.95)

0≤0.351.4

Missense OE?0.85 (0.76–0.96)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 10 / 17.9Missense obs/exp: 194 / 227.4Syn Z: 1.25

Background carrier burden — how many people carry a rare variant somewhere in PIP5KL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

610 rare PASS variants

Rare truncating (LoF)

1 in 610

102 rare PASS variants

Rare synonymous (reference)

1 in 170

268 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIP5KL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 550
South Asian	~43k	1 in 120	1 in 1,300
Remaining (unassigned)	~30k	1 in 86	1 in 570
European (Finnish)	~27k	1 in 240	1 in 1,800
Admixed American	~22k	1 in 96	1 in 940
African / African American	~21k	1 in 87	1 in 1,200
East Asian	~20k	1 in 160	1 in 3,600
Ashkenazi Jewish	~13k	1 in 450	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 72	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓