PHLDB2

Chr 3

pleckstrin homology like domain family B member 2

Also known as: LL5b, LL5beta

The PHLDB2 protein binds cadherins and is involved in assembling the postsynaptic apparatus, including acetylcholine receptor aggregation at the postsynaptic membrane. Mutations cause neurodevelopmental disorders with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.591).

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.59
Clinical SummaryPHLDB2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 4.01
OE 0.42 (0.300.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.38Z-score
OE missense 0.96 (0.901.02)
650 obs / 677.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.300.59)
00.351.4
Missense OE0.96 (0.901.02)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 23 / 55.1Missense obs/exp: 650 / 677.6Syn Z: -0.67
DN
0.7228th %ile
GOF
0.6247th %ile
LOF
0.4234th %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

PHLDB2 · 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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