PHLDB1

Chr 11AR

pleckstrin homology like domain family B member 1

Also known as: LL5A, LL5alpha, OI23

NCBI Gene: 23187ENSG00000019144UniProt: Q86UU1

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]

Primary Disease Associations & Inheritance

Osteogenesis imperfecta, type XXIIIMIM #620639
AR
248
ClinVar variants
29
Pathogenic / LP
0.11
pLI score
0
Active trials
Clinical Summary— PHLDB1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 207 VUS of 248 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.47Z-score
OE missense 0.86 (0.81–0.91)
732 obs / 853.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.16–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.81–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 15 / 62.0Missense obs/exp: 732 / 853.2Syn Z: 0.73

ClinVar Variant Classifications

248 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic2
VUS207
Likely Benign10
Benign2
27
Pathogenic
2
Likely Pathogenic
207
VUS
10
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
25
0
27
Likely Pathogenic
0
0
2
0
2
VUS
0
199
8
0
207
Likely Benign
0
4
1
5
10
Benign
0
1
0
1
2
Total2204366248

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Osteogenesis imperfecta, type XXIII

MIM #620639

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study.
Yang B et al.·Med Sci Monit
2015
Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes.
Tuysuz B et al.·J Med Genet
2023
A PHLDB1 variant associated with the nonfunctional pituitary adenoma.
Kim LH et al.·J Neurooncol
2019Functional
PHLDB1 and WDFY4 as dual-state biomarkers in SLE pathogenesis and lupus nephritis prediction.
Zhai J et al.·BMC Immunol
2026
Functional analysis of the 11q23.3 glioma susceptibility locus implicates PHLDB1 and DDX6 in glioma susceptibility.
Baskin R et al.·Sci Rep
2015Functional
New insights into susceptibility to glioma.
Liu Y et al.·Arch Neurol
2010Review
[OMICS and biomarkers of glial tumors].
Idbaih A·Rev Neurol (Paris)
2011Review
Genome-wide association study of glioma and meta-analysis.
Rajaraman P et al.·Hum Genet
2012Meta-analysis
Cancer susceptibility variants and the risk of adult glioma in a US case-control study.
Egan KM et al.·J Neurooncol
2011
Australian genome-wide association study confirms higher female risk for adult glioma associated with variants in the region of CCDC26.
Alpen K et al.·Neuro Oncol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools