PHLDB1

Chr 11AR

pleckstrin homology like domain family B member 1

Also known as: LL5A, LL5alpha, OI23

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.

OMIMResearchSummary from RefSeq, OMIM
DNmechanismARLOEUF 0.371 OMIM phenotype
Clinical SummaryPHLDB1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.107
Z-score 5.53
OE 0.24 (0.160.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.47Z-score
OE missense 0.86 (0.810.91)
732 obs / 853.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.160.37)
00.351.4
Missense OE0.86 (0.810.91)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 15 / 62.0Missense obs/exp: 732 / 853.2Syn Z: 0.73
DN
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PHLDB1 · 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

No active trials found for this gene.

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Clinical Literature
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