PHLDB1

Chr 11AR

pleckstrin homology like domain family B member 1

Also known as: LL5A, LL5alpha, OI23

NCBI Gene: 23187 ENSG00000019144 UniProt: Q86UU1 OMIM: 612834

The PHLDB1 protein regulates embryonic development, epithelial to mesenchymal transition, and microtubule cytoskeleton organization. Mutations cause osteogenesis imperfecta type XXIII with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.372), suggesting that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM

Involved in regulation of embryonic development; regulation of epithelial to mesenchymal transition; and regulation of microtubule cytoskeleton organization. Located in basal cortex. Implicated in osteogenesis imperfecta. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.371 OMIM phenotype

Clinical Summary— PHLDB1

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.37LOEUF

pLI 0.107

Z-score 5.53

OE 0.24 (0.16–0.37)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.47Z-score

OE missense 0.86 (0.81–0.91)

732 obs / 853.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.16–0.37)

0≤0.351.4

Missense OE?0.86 (0.81–0.91)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 15 / 62.0Missense obs/exp: 732 / 853.2Syn Z: 0.73

This gene — mechanism propensity

0.7133th %ile

GOF

0.6346th %ile

LOF

0.4528th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.