LBR

Chr 1ADAR

lamin B receptor

Also known as: C14SR, DHCR14B, LMN2R, PHA, PHASK, TDRD18

NCBI Gene: 3930ENSG00000143815UniProt: Q14739

The protein encoded by this gene belongs to the ERG4/ERG24 family. It localized in the nuclear envelope inner membrane and anchors the lamina and the heterochromatin to the membrane. It may mediate interaction between chromatin and lamin B. Mutations of this gene has been associated with autosomal recessive HEM/Greenberg skeletal dysplasia. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Reynolds syndromeMIM #613471
AD
Greenberg skeletal dysplasiaMIM #215140
AR
Pelger-Huet anomalyMIM #169400
AD
Rhizomelic skeletal dysplasia with or without Pelger-Huet anomalyMIM #618019
AR
UniProtGreenberg dysplasia
502
ClinVar variants
61
Pathogenic / LP
0.18
pLI score
1
Active trials
Clinical Summary— LBR
🧬
Gene-Disease Validity (ClinGen)
Greenberg dysplasia · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
61 Pathogenic / Likely Pathogenic· 243 VUS of 502 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.42LOEUF
pLI 0.181
Z-score 4.29
OE 0.24 (0.14–0.42)
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.
0.29Z-score
OE missense 0.96 (0.87–1.05)
337 obs / 352.3 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 (0.14–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.87–1.05)
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.0.87
0≤1.21.6
LoF obs/exp: 9 / 37.2Missense obs/exp: 337 / 352.3Syn Z: 1.19

ClinVar Variant Classifications

502 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic8
VUS243
Likely Benign124
Benign36
Conflicting38
53
Pathogenic
8
Likely Pathogenic
243
VUS
124
Likely Benign
36
Benign
38
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
6
39
0
53
Likely Pathogenic
3
4
1
0
8
VUS
1
205
35
2
243
Likely Benign
0
10
55
59
124
Benign
0
1
31
4
36
Conflicting
—38
Total1222616165502

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

View in ClinVar →

Protein Context — Lollipop Plot

LBR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LBR-related hydrops-ectopic calcification-moth-eaten skeletal dysplasia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
LAMIN B RECEPTOR; LBR
MIM #600024 · *

?Reynolds syndrome

MIM #613471

Molecular basis of disorder known

Autosomal dominant

Greenberg skeletal dysplasia

MIM #215140

Molecular basis of disorder known

Autosomal recessive

Pelger-Huet anomaly

MIM #169400

Molecular basis of disorder known

Autosomal dominant

Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly

MIM #618019

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis.
Vitagliano A et al.·Fertil Steril
2023Meta-analysis
The Effect of Uterine Adenomyosis on IVF Outcomes: a Systematic Review and Meta-analysis.
Cozzolino M et al.·Reprod Sci
2022Meta-analysis
Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis.
Mumusoglu S et al.·Fertil Steril
2025Meta-analysis
PGT-A: who and when? Α systematic review and network meta-analysis of RCTs.
Simopoulou M et al.·J Assist Reprod Genet
2021Review
Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis.
Cimadomo D et al.·Hum Reprod Update
2023Meta-analysis
The effect of progesterone supplementation for luteal phase support in natural cycle frozen embryo transfer: a systematic review and meta-analysis based on randomized controlled trials.
Jiang Y et al.·Fertil Steril
2023Meta-analysis
Does coenzyme Q(10) supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials.
Florou P et al.·J Assist Reprod Genet
2020Meta-analysis
Evenly Distributed Protein Intake over 3 Meals Augments Resistance Exercise-Induced Muscle Hypertrophy in Healthy Young Men.
Yasuda J et al.·J Nutr
2020
Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes.
Roque M et al.·Hum Reprod Update
2019Meta-analysis
Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles.
Sunkara SK et al.·Hum Reprod
2011
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
Healthy Volunteers

Black Raspberry Confection in Preventing Oral Cancer in Healthy Volunteers

ACTIVE NOT RECRUITING
NCT01961869Phase PHASE1Ohio State University Comprehensive Cancer CenterStarted 2013-07-02
Fast release BRB confectionIntermed release BRB confectionProlong release BRB confection

External Resources

Links to major genomics databases and tools