PLEKHB1

Chr 11

pleckstrin homology domain containing B1

Also known as: KPL1, PHR1, PHRET1

NCBI Gene: 58473 ENSG00000021300 UniProt: Q9UF11

The protein is predicted to enable protein homodimerization activity and regulate cell differentiation, and is located in cellular membranes. This gene is highly intolerant to loss-of-function variants (pLI = 0.0002), suggesting mutations would likely cause significant developmental effects. However, no specific disease associations have been established for PLEKHB1 mutations in current medical literature.

ResearchSummary from RefSeq

Predicted to enable protein homodimerization activity. Predicted to be involved in regulation of cell differentiation. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.59

OE 0.55 (0.32–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.41Z-score

OE missense 0.91 (0.80–1.04)

148 obs / 162.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.32–0.99)

0≤0.351.4

Missense OE?0.91 (0.80–1.04)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 8 / 14.5Missense obs/exp: 148 / 162.8Syn Z: 0.23

Background carrier burden — how many people carry a rare variant somewhere in PLEKHB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

384 rare PASS variants

Rare truncating (LoF)

1 in 380

94 rare PASS variants

Rare synonymous (reference)

1 in 290

151 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PLEKHB1; this gene does not show strong loss-of-function constraint by this measure. 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 150	1 in 1,300
South Asian	~43k	1 in 110	1 in 800
Remaining (unassigned)	~30k	1 in 95	1 in 1,300
European (Finnish)	~27k	1 in 380	1 in 3,800
Admixed American	~22k	1 in 140	1 in 980
African / African American	~21k	1 in 110	1 in 1,800
East Asian	~20k	1 in 82	1 in 1,700
Ashkenazi Jewish	~13k	1 in 670	none seen
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

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 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓