LBR

Summary

LBR (lamin B receptor, HGNC:6518) is a protein-coding gene on chromosome 1q42.12, encoding Delta(14)-sterol reductase LBR (Q14739). Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis.

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.

Source: NCBI Gene 3930 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Greenberg dysplasia (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 504 total — 21 pathogenic, 6 likely-pathogenic (top 7% of genes corpus-wide)
• GTEx eGene: eQTL in 27 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 199
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.97 (loss-of-function intolerant), LOEUF 0.50 (moderately constrained)
• MANE Select transcript: NM_002296
• Interaction hub: 2,114 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6518
Approved symbol	LBR
Name	lamin B receptor
Location	1q42.12
Locus type	gene with protein product
Status	Approved
Aliases	DHCR14B, TDRD18
Ensembl gene	ENSG00000143815
Ensembl biotype	protein_coding
OMIM	600024
Entrez	3930

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 30 protein_coding, 6 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000272163

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 5, TSL 5: 1

ENST00000272163, ENST00000338179, ENST00000421383, ENST00000424022, ENST00000425080, ENST00000441022, ENST00000487054, ENST00000488632, ENST00000651341, ENST00000885794, ENST00000885795, ENST00000885796, ENST00000885797, ENST00000885798, ENST00000885799, ENST00000885800, ENST00000885801, ENST00000885802, ENST00000885803, ENST00000933594, ENST00000933595, ENST00000933596, ENST00000933597, ENST00000945203, ENST00000945204, ENST00000945205, ENST00000945206, ENST00000945207, ENST00000945208, ENST00000945209, ENST00000992700, ENST00000992701, ENST00000992702, ENST00000992703, ENST00001042431, ENST00001100561, ENST00001112010, ENST00001112011, ENST00001130829, ENST00001143958

RefSeq mRNA: 2 — MANE Select: NM_002296 NM_002296, NM_194442

CCDS: CCDS1545

Canonical transcript exons

ENST00000272163 — 14 exons

Exon	Start	End
ENSE00000962089	225422077	225422277
ENSE00001071015	225423911	225424089
ENSE00001892518	225401502	225403463
ENSE00001894160	225427954	225428038
ENSE00002219018	225412454	225412645
ENSE00002219833	225415278	225415332
ENSE00002247606	225411337	225411440
ENSE00002254361	225417984	225418180
ENSE00002279308	225404626	225404706
ENSE00002281815	225419715	225419798
ENSE00002284747	225406664	225406832
ENSE00002307138	225404404	225404526
ENSE00003754323	225410291	225410416
ENSE00003788743	225419263	225419452

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.1700 / max 834.4108, expressed in 1813 samples.

Highest expression (Bgee): trabecular bone tissue, bone marrow, thymus, bone marrow cell, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LBR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	2.9e-83	+0.85	1:225447781:C:T
Esophagus Muscularis	eqtl	5.2e-42	+0.48	1:225447979:A:G
Pancreas	eqtl	4.7e-35	+0.65	1:225409161:A:AAT
Esophagus Gastroesophageal Junction	eqtl	2.2e-34	+0.58	1:225447781:C:T
Artery Coronary	eqtl	7.5e-22	+0.70	1:225460342:C:A
Nerve Tibial	eqtl	8.7e-21	+0.41	1:225443505:G:A
Heart Atrial Appendage	eqtl	7.2e-16	+0.52	1:225464109:C:T
Artery Aorta	eqtl	3.0e-13	+0.33	1:225447781:C:T
Colon Sigmoid	sqtl	5.9e-10	+0.47	1:225461806:G:A
Colon Sigmoid	eqtl	1.4e-09	+0.21	1:225461806:G:A
Adipose Subcutaneous	eqtl	1.5e-09	+0.24	1:225438447:T:G
Testis	eqtl	1.5e-09	-0.19	1:225427864:G:C
Cells Cultured fibroblasts	eqtl	6.8e-05	+0.38	1:225397820:C:G
Stomach	eqtl	1.2e-04	+0.17	1:225443505:G:A
Muscle Skeletal	eqtl	3.0e-04	-0.15	1:225431755:T:C
Brain Cerebellar Hemisphere	eqtl	4.2e-04	+0.29	1:225461987:A:C
Esophagus Mucosa	eqtl	6.6e-04	+0.14	1:225399808:C:T
Stomach	sqtl	2.3e-03	-1.23	1:225753752:C:T
Lung	eqtl	3.7e-03	-0.26	1:225366080:C:T
Adrenal Gland	eqtl	6.0e-03	+0.31	1:225453839:A:G

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
17691	39.1181	1813
17692	1.2233	682
17693	0.5910	330
17690	0.2377	108

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	98.89	gold quality
bone marrow	UBERON:0002371	98.39	gold quality
thymus	UBERON:0002370	98.10	gold quality
bone marrow cell	CL:0002092	97.79	gold quality
ventricular zone	UBERON:0003053	97.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.85	gold quality
seminal vesicle	UBERON:0000998	96.82	gold quality
vermiform appendix	UBERON:0001154	96.79	gold quality
caecum	UBERON:0001153	96.72	gold quality
sigmoid colon	UBERON:0001159	96.71	gold quality
visceral pleura	UBERON:0002401	96.69	gold quality
monocyte	CL:0000576	96.65	gold quality
mononuclear cell	CL:0000842	96.65	gold quality
leukocyte	CL:0000738	96.58	gold quality
blood	UBERON:0000178	96.41	gold quality
rectum	UBERON:0001052	96.35	gold quality
colonic epithelium	UBERON:0000397	96.32	gold quality
lymph node	UBERON:0000029	96.26	gold quality
secondary oocyte	CL:0000655	96.25	gold quality
pleura	UBERON:0000977	96.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.09	gold quality
parietal pleura	UBERON:0002400	96.01	gold quality
colonic mucosa	UBERON:0000317	95.98	gold quality
embryo	UBERON:0000922	95.94	gold quality
large intestine	UBERON:0000059	95.80	gold quality
corpus epididymis	UBERON:0004359	95.80	gold quality
cauda epididymis	UBERON:0004360	95.80	gold quality
colon	UBERON:0001155	95.76	gold quality
superficial temporal artery	UBERON:0001614	95.76	gold quality
saphenous vein	UBERON:0007318	95.61	gold quality
myometrium	UBERON:0001296	95.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.53	gold quality
body of uterus	UBERON:0009853	95.51	gold quality
lower esophagus	UBERON:0013473	95.51	gold quality
ganglionic eminence	UBERON:0004023	95.47	gold quality
left uterine tube	UBERON:0001303	95.38	gold quality
tongue squamous epithelium	UBERON:0006919	95.38	gold quality
intestine	UBERON:0000160	95.18	gold quality
pylorus	UBERON:0001166	95.08	gold quality
duodenum	UBERON:0002114	94.86	gold quality
transverse colon	UBERON:0001157	94.78	gold quality
urinary bladder	UBERON:0001255	94.73	gold quality
jejunal mucosa	UBERON:0000399	94.69	gold quality
tibia	UBERON:0000979	94.65	gold quality
esophagus squamous epithelium	UBERON:0006920	94.51	gold quality
blood vessel layer	UBERON:0004797	94.50	gold quality
uterus	UBERON:0000995	94.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.31	gold quality
ileal mucosa	UBERON:0000331	94.11	gold quality
endometrium	UBERON:0001295	94.10	gold quality
urethra	UBERON:0000057	93.97	gold quality
endothelial cell	CL:0000115	93.85	gold quality
renal medulla	UBERON:0000362	93.82	gold quality
ectocervix	UBERON:0012249	93.81	gold quality
esophagus	UBERON:0001043	93.69	gold quality
periodontal ligament	UBERON:0008266	93.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.63	gold quality
epithelium of nasopharynx	UBERON:0001951	93.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.52	gold quality
tonsil	UBERON:0002372	93.46	gold quality
mucosa of urinary bladder	UBERON:0001259	93.41	gold quality
tibial artery	UBERON:0007610	93.40	gold quality
oocyte	CL:0000023	93.39	gold quality
popliteal artery	UBERON:0002250	93.39	gold quality
small intestine	UBERON:0002108	93.20	gold quality
squamous epithelium	UBERON:0006914	93.07	gold quality
fundus of stomach	UBERON:0001160	93.06	gold quality
pericardium	UBERON:0002407	92.99	gold quality
female reproductive system	UBERON:0000474	92.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.87	gold quality
epithelium of esophagus	UBERON:0001976	92.80	gold quality
mucosa of stomach	UBERON:0001199	92.77	gold quality
smooth muscle tissue	UBERON:0001135	92.76	gold quality
vena cava	UBERON:0004087	92.68	gold quality
nipple	UBERON:0002030	92.67	gold quality
vagina	UBERON:0000996	92.66	gold quality
lower lobe of lung	UBERON:0008949	92.47	gold quality
cardia of stomach	UBERON:0001162	92.45	gold quality
amniotic fluid	UBERON:0000173	92.44	gold quality
spleen	UBERON:0002106	92.44	gold quality
nephron tubule	UBERON:0001231	92.42	gold quality
caput epididymis	UBERON:0004358	92.22	gold quality
oral cavity	UBERON:0000167	92.20	gold quality
endocervix	UBERON:0000458	92.18	gold quality
gall bladder	UBERON:0002110	92.15	gold quality
right lung	UBERON:0002167	92.07	gold quality
skin of hip	UBERON:0001554	92.02	gold quality
esophagus mucosa	UBERON:0002469	92.01	gold quality
jejunum	UBERON:0002115	91.99	gold quality
granulocyte	CL:0000094	91.81	gold quality
choroid plexus epithelium	UBERON:0003911	91.73	gold quality
mucosa of transverse colon	UBERON:0004991	91.70	gold quality
gingival epithelium	UBERON:0001949	91.66	gold quality
fallopian tube	UBERON:0003889	91.61	gold quality
right ovary	UBERON:0002118	91.57	gold quality
lung	UBERON:0002048	91.51	gold quality
ovary	UBERON:0000992	91.37	gold quality
adipose tissue	UBERON:0001013	91.23	gold quality
liver	UBERON:0002107	91.15	gold quality
connective tissue	UBERON:0002384	91.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.69
E-CURD-88	no	3.71

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	98.3
Bone marrow	tissue	90.3	high
Lymph node	tissue	76.2	high
Tonsil	tissue	66.2	high
Appendix	tissue	50.2	high
Liver	tissue	44.3	high
Endometrium 1	tissue	44.0	medium
Rectum	tissue	43.4	high
Epididymis	tissue	41.9	medium
Colon	tissue	40.7	high
Spleen	tissue	39.1	high
Smooth muscle	tissue	38.6	medium
Duodenum	tissue	38.3	high
Small intestine	tissue	37.6	high
Seminal vesicle	tissue	34.6	low
Esophagus	tissue	27.9	medium
Adipose tissue	tissue	26.8	not detected
Urinary bladder	tissue	26.0	not detected
Placenta	tissue	26.0	not detected
Prostate	tissue	22.3	low
Vagina	tissue	21.1	low
Cervix	tissue	20.6	low
Gallbladder	tissue	20.4	high
Testis	tissue	19.2	high
Stomach 1	tissue	18.4	medium
Lung	tissue	18.1	high
Kidney	tissue	18.1	medium
Fallopian tube	tissue	17.5	low
Ovary	tissue	17.2	not detected
Pancreas	tissue	15.3	high
Skin 1	tissue	13.0	not detected
Spinal cord	tissue	12.9
Corpus callosum	tissue	12.3
Hypothalamus	tissue	12.1
Tongue	tissue	11.9
Choroid plexus	tissue	11.2
Substantia nigra	tissue	11.2
Breast	tissue	10.9	low
Septum	tissue	10.8
Pons	tissue	10.5
Midbrain	tissue	10.2
Medulla oblongata	tissue	10.2
Periaqueductal gray	tissue	10.1
Locus coeruleus	tissue	10.0
Thalamus	tissue	9.4
Thyroid gland	tissue	9.4	medium
Nucleus accumbens	tissue	8.9
Superior colliculi	tissue	8.8
Hippocampus	tissue	8.8	medium
Adrenal gland	tissue	8.6	medium
Skeletal muscle	tissue	8.5	high
Salivary gland	tissue	8.3	not detected
Ventral forebrain	tissue	8.1
Heart muscle	tissue	7.7	medium
Putamen	tissue	7.5
Amygdala	tissue	7.5
Hippocampal formation	tissue	7.3
Basal ganglia	tissue	6.7	medium
Postcentral gyrus	tissue	6.4
Olfactory bulb	tissue	6.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (27.2), Corpus callosum, splenium (white matter) (18.8), Corpus callosum, genu (white matter) (18.4), Parieto-temporal junction (white matter) (17.6), Cerebellar white matter (17.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPE, GLI2, MYC, NFKB, SP1

miRNA regulators (miRDB)

Targeting LBR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 144 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883

Functional genomics

gnomAD constraint: pLI 0.973, LOEUF 0.499, missense Z 0.949 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000272163 — one region, missense o/e 0.94. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The binding of lamin B receptor to chromatin is regulated by phosphorylation in the arginine-serine repeat-containing REGION (PMID:11846796)
• Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huet anomaly). (PMID:12118250)
• Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in this gene. (PMID:12618959)
• examination of temporal association with protamine 1 during spermiogenesis (PMID:14701833)
• SR protein kinase and cdc2 kinase regulate lamin B receptor binding to chromatin (PMID:14718546)
• MeCP2 interacts in vitro and in vivo with the inner nuclear membrane protein LBR, and the unstructured aminoacidic sequence linking the MBD and TRD domains of MeCP2 is responsible for this association. (PMID:19331822)
• results suggest that LMNA, ZMPSTE24, and LBR sequence variations are not major genetic determinants involved in scleroderma pathogenesis (PMID:19645629)
• LBR mutant variants and sterol reductases can severely interfere with the regular organization of the nuclear envelope and the endoplasmic reticulum. (PMID:19940018)
• LBR targets the membrane precursor vesicles to chromatin by interacting with importin beta in a LBR phosphorylation-dependent manner during the NE assembly at the end of mitosis (PMID:20576617)
• LBR is heavily expressed in papillary thyroid carcinoma cells, but an abnormal folding of the protein might explain its lack of immunohistochemical reactivity and be associated with the anomalous folding of the nuclear membrane. (PMID:21103616)
• a highly significant gene-dosage effect between the gene copy number and the nuclear segmentation index of neutrophils (PMID:21326950)
• LBR missense mutations can abolish sterol reductase activity, causing lethal Greenberg dysplasia but not Pelger anomaly (PMID:21327084)
• The LBR knockdown cells retain an ovoid shaped nucleus with reduced levels of lamin A/C during in vitro granulopoiesis induced with retinoic acid. (PMID:21327094)
• Our studies reveal for the first time a mechanism that controls the timing of nuclear envelope reassembly through modification of the integral nuclear membrane protein lamin B receptor (PMID:21795390)
• Lymphohematopoietic licence: sterol C-14 reductase activity of lamin B receptor (Lbr) is essential for neutrophil differentiation. (PMID:22581323)
• Mutation in LBR gene is associated with pelger-huet anomaly and a mild skeletal phenotype. (PMID:23824842)
• Lamin B receptor mRNA expression was directly associated with tumor grade in breast cancer patients(grade 1 vs. grade 3 - 0.00 vs. 0.00; p = 0.0479) and Nottingham Prognostic Index (NPI1 vs. NPI3 - 0.00 vs. 0.00; p = 0.0551). (PMID:24293108)
• We have shown here that lamin B receptor (LBR) showed a change in localization in both BrdU-induced and replicative senescent cells. (PMID:27059139)
• Data indicate that proto-oncogene protein c-akt (Akt) phosphorylates distinct sites than SRPK1 protein within the arginine-serine (RS) domain of Lamin B Receptor (LBR). (PMID:27105349)
• The authors demonstrate that human LBR is essential for cholesterol synthesis. (PMID:27336722)
• The primary response of cells to various stresses leading to senescence consists of the down-regulation of LBR and LB1 to attain reversal of the chromatin architecture. (PMID:27760841)
• These observations point to a new mechanism regulating the localization of LBR, which is governed by an ELYS-mediated phosphorylation network. (PMID:27802161)
• This report provides further evidence for a phenotypic spectrum of LBR-associated disorders and expands the genotypic spectrum by describing 3 novel disease-causing variants that have not been previously associated with a disease. (PMID:30448303)
• A common pathogenic mechanism in GMAP-210- and LBR-related diseases attributable to defective secretory trafficking at the Golgi apparatus. (PMID:30518689)
• LBR represents an instructive example of one gene presenting with two different patterns of inheritance and at least three different clinical phenotypes. (PMID:30561119)
• These results suggested that decreased LBR function is involved in the induction of cellular senescence in human cells. (PMID:30615890)
• MiR-222/LBR have key roles in controlling pro-progression influences of cancer-associated fibroblasts in breast cancer. (PMID:31481734)
• The c.893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the Pelger-Husmall io, Russiant anomaly in this pedigree (PMID:31515787)
• Lamin B receptor plays a key role in cellular senescence induced by inhibition of the proteasome. (PMID:31825172)
• Twin enzymes, divergent control: The cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally. (PMID:31911440)
• The role of lamin B receptor in the regulation of senescence-associated secretory phenotype (SASP). (PMID:32126237)
• TMEM147 interacts with lamin B receptor, regulates its localization and levels, and affects cholesterol homeostasis. (PMID:32694168)
• A homozygous variant in the Lamin B receptor gene LBR results in a non-lethal skeletal dysplasia without Pelger-Huet anomaly. (PMID:32827848)
• Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor. (PMID:33958580)
• Reduction of lamin B receptor levels by miR-340-5p disrupts chromatin, promotes cell senescence and enhances senolysis. (PMID:34181735)
• Knockdown of Lamin B1 and the Corresponding Lamin B Receptor Leads to Changes in Heterochromatin State and Senescence Induction in Malignant Melanoma. (PMID:35883595)
• Nuclear envelope protein lamin B receptor protects the genome from chromosomal instability and tumorigenesis. (PMID:36124691)
• Natural history and genetic spectrum of the Turkish metaphyseal dysplasia cohort, including rare types caused by biallelic COL10A1, COL2A1, and LBR variants. (PMID:36400164)
• Differentiation-dependent changes in lamin B1 dynamics and lamin B receptor localization. (PMID:36598800)
• Upregulated expression of lamin B receptor increases cell proliferation and suppresses genomic instability: implications for cellular immortalization. (PMID:38462947)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lbr	ENSDARG00000014013
mus_musculus	Lbr	ENSMUSG00000004880
rattus_norvegicus	Lbr	ENSRNOG00000052574
drosophila_melanogaster	LBR	FBGN0034657

Paralogs (2): TM7SF2 (ENSG00000149809), DHCR7 (ENSG00000172893)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2138281) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 109 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal neutrophil morphology	4
scaly skin	3
abnormal lymphocyte morphology	3
abnormal coat/ hair morphology	2
sparse hair	2
syndactyly	2
enlarged lymph nodes	2
abnormal epidermal layer morphology	2
postnatal growth retardation	2
male infertility	2
abnormal blood cell morphology/development	2
abnormal granulocyte morphology	2
abnormal cell nucleus morphology	2
decreased lymphocyte cell number	2
prenatal lethality, incomplete penetrance	2
decreased bone mineral density	1
abnormal trabecular bone morphology	1
abnormal rib morphology	1
scoliosis	1
increased neutrophil cell number	1
increased monocyte cell number	1
decreased leukocyte cell number	1
delayed hair appearance	1
abnormal cranium morphology	1
abnormal forelimb morphology	1

+84 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R7H4	97.1%	Diamond
Xenopus tropicalis	Q6P4M0	95.1%	Diamond
Xenopus laevis	Q7ZXH1	95.1%	Diamond
Bos taurus	Q8WMV1	90.0%	Diamond
Fusarium graminearum PH-1	I1RR90	84.1%	Diamond
Fusarium vanettenii	Q01447	84.1%	Diamond
Aspergillus fumigatus Af293	Q4WJJ9	76.4%	Diamond
Neurospora crassa OR74A	P38670	68.1%	Diamond
Gallus gallus	P23913	65.3%	Diamond
Saccharomyces cerevisiae S288C	P25340	61.9%	Diamond
Candida albicans SC5314	A0A1D8PIC7	58.3%	Diamond
Septoria lycopersici	O13597	56.3%	Diamond
Schizosaccharomyces pombe 972h-	P36209	54.1%	Diamond
Ascobolus immersus	P78575	48.4%	Diamond
Methylotuvimicrobium alcaliphilum 20Z	G4SW86	46.1%	Diamond
Dictyostelium discoideum	Q54PP1	44.3%	Diamond
Arabidopsis thaliana	Q9LDR4	43.2%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UQI4	53.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02813	ncRNA	107985338
DNAH14	protein-coding	127602
ENAH	protein-coding	55740
LINC02765	ncRNA	105373110

Protein

Protein identifiers

Delta(14)-sterol reductase LBR — Q14739 (reviewed: Q14739)

Alternative names: 3-beta-hydroxysterol Delta (14)-reductase, C-14 sterol reductase, Integral nuclear envelope inner membrane protein, LMN2R, Lamin-B receptor, Sterol C14-reductase

All UniProt accessions (4): A0A494C1L1, C9JES9, C9JXK0, Q14739

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis. Plays a critical role in myeloid cell cholesterol biosynthesis which is essential to both myeloid cell growth and functional maturation. Mediates the activation of NADPH oxidases, perhaps by maintaining critical levels of cholesterol required for membrane lipid raft formation during neutrophil differentiation. Anchors the lamina and the heterochromatin to the inner nuclear membrane.

Subunit / interactions. Interacts with CBX5. Interacts with DNA. Interaction with DNA is sequence independent with higher affinity for supercoiled and relaxed circular DNA than linear DNA. Interacts with lamin B. Interacts with CLNK. Interacts with TMEM147; promoting LBR localization to the nucleus inner membrane.

Subcellular location. Nucleus inner membrane. Endoplasmic reticulum membrane. Cytoplasm. Nucleus.

Tissue specificity. Expressed in the bone marrow, liver, heart, adrenal gland, lung, placenta and uterus. Expressed in osteoclasts and osteoblast-like cells.

Post-translational modifications. Phosphorylated by CDK1 in mitosis when the inner nuclear membrane breaks down into vesicles that dissociate from the lamina and the chromatin. It is phosphorylated by different protein kinases in interphase when the membrane is associated with these structures. Phosphorylation of LBR and HP1 proteins may be responsible for some of the alterations in chromatin organization and nuclear structure which occur at various times during the cell cycle. Phosphorylated by SRPK1. In late anaphase LBR is dephosphorylated, probably by PP1 and/or PP2A, allowing reassociation with chromatin.

Disease relevance. Pelger-Huet anomaly (PHA) [MIM:169400] An autosomal dominant inherited abnormality of granulocytes, characterized by abnormal ovoid shape, reduced nuclear segmentation and an apparently looser chromatin structure. The disease is caused by variants affecting the gene represented in this entry. Greenberg dysplasia (GRBGD) [MIM:215140] A rare autosomal recessive chondrodystrophy characterized by early in utero lethality. Affected fetuses typically present with fetal hydrops, short-limbed dwarfism, and a marked disorganization of chondro-osseous calcification, and ectopic ossification centers. The disease is caused by variants affecting the gene represented in this entry. Reynolds syndrome (REYNS) [MIM:613471] A syndrome specifically associating limited cutaneous systemic sclerosis and primary biliary cirrhosis. It is characterized by liver disease, telangiectasia, abrupt onset of digital paleness or cyanosis in response to cold exposure or stress (Raynaud phenomenon), and variable features of scleroderma. The liver disease is characterized by pruritis, jaundice, hepatomegaly, increased serum alkaline phosphatase and positive serum mitochondrial autoantibodies, all consistent with primary biliary cirrhosis. The disease may be caused by variants affecting the gene represented in this entry. Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly (SKPHA) [MIM:618019] A disease characterized by abnormal nuclear shape and chromatin organization in blood granulocytes, short stature, and mild skeletal anomalies. Initial skeletal features may improve with age. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The Tudor domain may not recognize methylation marks, but rather bind unassembled free histone H3.

Pathway. Steroid biosynthesis; cholesterol biosynthesis.

Similarity. Belongs to the ERG4/ERG24 family.

RefSeq proteins (2): NP_002287, NP_919424 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001171	ERG24_DHCR-like	Family
IPR002999	Tudor	Domain
IPR018083	Sterol_reductase_CS	Conserved_site
IPR019023	Lamin-B_rcpt_of_tudor	Domain

Pfam: PF01222, PF09465

Enzyme classification (BRENDA)

• EC 1.3.1.70 — DELTA14-sterol reductase (BRENDA: 16 organisms, 57 substrates, 84 inhibitors, 12 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4,4-DIMETHYL-5ALPHA-CHOLESTA-7,14-DIEN-3BETA-OL	0.0294–0.0345	3
NADPH	0.023–0.6	2
4ALPHA-METHYL-5ALPHA-ERGOSTA-8,14,24(28)-TRIEN-3	0.1	1
5ALPHA-CHOLESTA-8,14-DIEN-3BETA-OL	0.45	1
ERGOSTA-8,14-DIEN-3BETA-OL	0.06	1

Catalyzed reactions (Rhea)

• 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H(+) (RHEA:18561)
• 5alpha-cholest-8,14-dien-3beta-ol + NADPH + H(+) = 5alpha-cholest-8-en-3beta-ol + NADP(+) (RHEA:46456)
• 4,4-dimethyl-8,14-cholestadien-3beta-ol + NADPH + H(+) = 4,4-dimethyl-5alpha-cholest-8-en-3beta-ol + NADP(+) (RHEA:46812)

UniProt features (47 total): modified residue 13, sequence variant 11, transmembrane region 8, strand 4, sequence conflict 3, turn 3, chain 1, topological domain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2DIG	Solusion structure of the Todor domain of human Lamin-B receptor	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14739-F1	76.89	0.46

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the musculoskeletal system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear membrane; nucleoli fibrillar center

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (13)

Type	Positions
N6-acetyllysine	55, 594, 601
Phosphothreonine	58, 118, 200
Phosphoserine	59, 67, 71, 86, 97, 99, 128

Function

Pathways and Gene Ontology

Reactome pathways

11 curated (TAS) of 29; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

29 pathways:

ID	Pathway	Evidence
R-HSA-9013148	CDC42 GTPase cycle	curated
R-HSA-6807047	Cholesterol biosynthesis via desmosterol (Bloch pathway)	curated
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation	curated
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013404	RAC2 GTPase cycle	curated
R-HSA-9013423	RAC3 GTPase cycle	curated
R-HSA-8980692	RHOA GTPase cycle	curated
R-HSA-9013106	RHOC GTPase cycle	curated
R-HSA-9013405	RHOD GTPase cycle	curated
R-HSA-9013408	RHOG GTPase cycle	curated
R-HSA-9022692	Regulation of MECP2 expression and activity	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-191273	Cholesterol biosynthesis	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-68886	M Phase	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-8957322	Metabolism of steroids	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-2995410	Nuclear Envelope (NE) Reassembly	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-8986944	Transcriptional Regulation by MECP2	—

MSigDB gene sets: 737 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, MORF_DNMT1, MODULE_97, HORIUCHI_WTAP_TARGETS_DN, MODULE_151, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, MATTIOLI_MGUS_VS_PCL, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MODULE_182, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (9): cholesterol biosynthetic process (GO:0006695), neutrophil differentiation (GO:0030223), zymosterol biosynthetic process (GO:0036197), random inactivation of X chromosome (GO:0060816), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), sterol biosynthetic process (GO:0016126)

GO Molecular Function (10): DNA binding (GO:0003677), RNA binding (GO:0003723), lamin binding (GO:0005521), Delta14-sterol reductase activity (GO:0050613), chromo shadow domain binding (GO:0070087), NADPH binding (GO:0070402), chromatin-protein adaptor activity (GO:0140463), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor (GO:0016628)

GO Cellular Component (8): nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), nuclear lamina (GO:0005652), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nuclear membrane (GO:0031965)

Reactome top-level categories

10 top-level categories:

Category	Pathways
RHO GTPase cycle	8
Nuclear Envelope (NE) Reassembly	1
Cholesterol biosynthesis	1
Transcriptional Regulation by MECP2	1
Metabolism of steroids	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
RNA Polymerase II Transcription	1
M Phase	1
Mitotic Anaphase	1
Metabolism	1

GO top-level categories

38 GO namespaces:

Category	Terms
cellular anatomical structure	3
sterol biosynthetic process	2
secondary alcohol biosynthetic process	2
sterol metabolic process	2
nucleic acid binding	2
nucleus	2
nuclear envelope	2
organelle membrane	2
cholesterol metabolic process	1
granulocyte differentiation	1
zymosterol metabolic process	1
dosage compensation by inactivation of X chromosome	1
primary metabolic process	1
steroid metabolic process	1
lipid biosynthetic process	1
lipid metabolic process	1
secondary alcohol metabolic process	1
steroid biosynthetic process	1
protein binding	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
protein domain specific binding	1
anion binding	1
NADP binding	1
chromatin binding	1
chromatin organization	1
protein-macromolecule adaptor activity	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the CH-CH group of donors	1
intracellular membrane-bounded organelle	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
nuclear periphery	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
cholesterol biosynthetic process	BP	direct assay
cytoplasm	CC	direct assay
endoplasmic reticulum membrane	CC	direct assay
membrane	CC	direct assay
nuclear inner membrane	CC	direct assay
nuclear membrane	CC	direct assay
nucleus	CC	direct assay
Delta14-sterol reductase activity	MF	direct assay
NADPH binding	MF	mutant phenotype
RNA binding	MF	high-throughput assay
chromo shadow domain binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,114 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LBR	LMNB2	Q03252	893
LBR	LMNB1	P20700	883
LBR	FDFT1	P37268	855
LBR	EMD	P50402	851
LBR	LEMD3	Q9Y2U8	767
LBR	SUN2	Q9UH99	743
LBR	CBX5	P45973	725
LBR	NRM	Q8IXM6	717
LBR	BANF2	Q9H503	700
LBR	BANF1	O75531	694
LBR	SUN1	O94901	691
LBR	EBP	Q15125	678
LBR	NUP153	P49790	672
LBR	CBX1	P23197	671
LBR	TMPO	P08918	670

IntAct

Human interaction partners of LBR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAG	physical association	0.750	2
MAD2L1BP	association	0.730	2
CBX3	physical association	0.620	2
CBX5	association	0.610	4
CD81	physical association	0.560	3
C1QBP	physical association	0.560	1
YWHAB	physical association	0.560	1
ZNF579	physical association	0.560	1
SRPK1	phosphorylation reaction	0.440	1
H3-4	physical association	0.400	1
VSTM4	physical association	0.400	1
WASH3P	physical association	0.400	1
PB2	physical association	0.370	1
CDC123	association	0.350	1
RPL17	association	0.350	1
TERF2	association	0.350	1
MYC	physical association	0.000	1
PHLDA3	physical association	0.000	1

BioGRID (405 interactions; top human partners by supporting records): LMNA (Affinity Capture-MS; 6 records), CBX5 (Two-hybrid; 5 records), MECP2 (Co-fractionation; 5 records), LUC7L (Affinity Capture-MS; 4 records), C1QBP (Proximity Label-MS; 3 records), CANX (Affinity Capture-MS; 3 records), CBX3 (Two-hybrid; 3 records), HIST1H3A (Affinity Capture-MS; 3 records), PARK2 (Affinity Capture-MS; 3 records), RAC1 (Affinity Capture-MS; 3 records), TGOLN2 (Affinity Capture-MS; 3 records), YWHAG (Affinity Capture-MS; 3 records), ARF6 (Proximity Label-MS; 2 records), BHLHA15 (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CDK1	down-regulates	LBR	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for LBR: 504 ClinVar records (27 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

504 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	6
Uncertain significance	245
Likely benign	123
Benign	34

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 27 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
100901	NM_002296.4(LBR):c.1748G>A (p.Arg583Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
224876	NM_002296.4(LBR):c.226C>T (p.Arg76Ter)	Pathogenic	criteria provided, single submitter	3
419545	NM_002296.4(LBR):c.1748G>T (p.Arg583Leu)	Pathogenic	criteria provided, single submitter	2
1390897	NM_002296.4(LBR):c.1741_1742del (p.Val581fs)	Pathogenic	criteria provided, single submitter	1
1441841	NM_002296.4(LBR):c.403dup (p.Glu135fs)	Pathogenic	criteria provided, single submitter	1
2078992	NM_002296.4(LBR):c.638dup (p.Gly214fs)	Pathogenic	criteria provided, single submitter	1
2106050	NM_002296.4(LBR):c.1A>G (p.Met1Val)	Pathogenic	criteria provided, single submitter	1
2151919	NM_002296.4(LBR):c.43C>T (p.Arg15Ter)	Pathogenic	criteria provided, single submitter	1
4538625	NM_002296.4(LBR):c.48G>A (p.Trp16Ter)	Pathogenic	criteria provided, single submitter	1
4803593	NM_002296.4(LBR):c.265C>T (p.Arg89Ter)	Pathogenic	criteria provided, single submitter	1
446676	NM_002296.4(LBR):c.1174G>A (p.Gly392Arg)	Likely pathogenic	criteria provided, single submitter	3
1676661	NM_002296.4(LBR):c.235C>T (p.Arg79Ter)	Likely pathogenic	criteria provided, single submitter	1
2635414	NM_002296.4(LBR):c.1430_1433del (p.Ser477fs)	Likely pathogenic	criteria provided, single submitter	1
4721476	NM_002296.4(LBR):c.1483+2T>A	Likely pathogenic	criteria provided, single submitter	1
4853933	NM_002296.4(LBR):c.1534C>T (p.Arg512Trp)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore LBR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 1,205):

Position(s)	Effect	Δscore	Sites
1:225404624–225404625	donor_loss	1.0000	3
1:225406833–225406834	acceptor_loss	1.0000	4
1:225422076	donor_loss	1.0000
1:225422109	donor_gain	1.0000
1:225423909–225423910	donor_loss	1.0000	4
1:225427953	donor_loss	1.0000
1:225403418	acceptor_gain	0.9900
1:225403433	acceptor_gain	0.9900
1:225403464–225403465	acceptor_loss	0.9900	6
1:225404402–225404403	donor_loss	0.9900	6

AlphaMissense

1,069 missense substitutions predicted likely pathogenic (of 4,012 scored), across 300 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D551	8	0.967	0.985
H545	8	0.961	0.997
D446	8	0.957	0.979
D382	8	0.953	0.974
D43	8	0.936	0.986
D587	8	0.931	0.980
F501	8	0.915	0.991
D433	8	0.899	0.948
S19	8	0.833	0.991
F452	8	0.820	0.939
W16	7	0.988	0.998
W599	7	0.985	0.996
W540	7	0.982	0.996
F511	7	0.963	0.990
C591	7	0.940	0.986
K508	7	0.936	0.997
F6	7	0.925	0.985
E438	7	0.925	0.983
W396	7	0.906	0.991
N547	7	0.893	0.987

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000328
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00049

Disease associations

OMIM: gene MIM:600024 | disease phenotypes: MIM:169400, MIM:215140, MIM:613471, MIM:618019, MIM:208500

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
Greenberg dysplasia	Definitive	Autosomal recessive	6
Pelger-Huet anomaly	Strong	Autosomal dominant	2
regressive spondylometaphyseal dysplasia	Strong	Autosomal recessive	3

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
Greenberg dysplasia	Moderate	AR
regressive spondylometaphyseal dysplasia	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (13 panels, 13 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

13 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Fetal hydrops	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Limb disorders	green
Paediatric disorders	green
Rare multisystem ciliopathy Super panel	green
Skeletal ciliopathies	green
Skeletal dysplasia	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (5): Pelger-Huet anomaly (MONDO:0008214), Greenberg dysplasia (MONDO:0008974), Reynolds syndrome (MONDO:0013276), regressive spondylometaphyseal dysplasia (MONDO:0018663), Jeune syndrome (MONDO:0018770)

Orphanet (4): Greenberg dysplasia (Orphanet:1426), Regressive spondylometaphyseal dysplasia (Orphanet:448267), Reynolds syndrome (Orphanet:779), Jeune syndrome (Orphanet:474)

HPO phenotypes

showing 60 of 199 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000212	Gingival overgrowth
HP:0000214	Lip telangiectasia
HP:0000217	Xerostomia
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000336	Prominent supraorbital ridges
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000457	Depressed nasal ridge
HP:0000476	Cystic hygroma
HP:0000486	Strabismus
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000782	Abnormal scapula morphology
HP:0000878	11 pairs of ribs
HP:0000888	Horizontal ribs
HP:0000890	Long clavicle
HP:0000926	Platyspondyly
HP:0000952	Jaundice
HP:0000964	Eczematoid dermatitis
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001004	Lymphedema
HP:0001097	Keratoconjunctivitis sicca
HP:0001156	Brachydactyly
HP:0001162	Postaxial hand polydactyly
HP:0001169	Broad palm
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001362	Calvarial skull defect
HP:0001369	Arthritis
HP:0001373	Joint dislocation
HP:0001377	Limited elbow extension
HP:0001382	Joint hypermobility
HP:0001394	Cirrhosis
HP:0001396	Cholestasis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001537	Umbilical hernia
HP:0001538	Protuberant abdomen
HP:0001541	Ascites
HP:0001552	Barrel-shaped chest
HP:0001561	Polyhydramnios
HP:0001629	Ventricular septal defect
HP:0001744	Splenomegaly
HP:0001761	Pes cavus
HP:0001789	Hydrops fetalis
HP:0001790	Nonimmune hydrops fetalis
HP:0001830	Postaxial foot polydactyly
HP:0001873	Thrombocytopenia
HP:0001874	Abnormality of neutrophils

GWAS associations

5 associations:

Study	Trait	p-value
GCST90002392_41	Mean corpuscular volume	2e-12
GCST90002397_287	Mean spheric corpuscular volume	5e-10
GCST011741_56	LDL cholesterol levels in HIV infection	2e-6
GCST011741_74	LDL cholesterol levels in HIV infection	2e-6
GCST005851_23	Delirium	4e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D010381	Pelger-Huet Anomaly	C15.378.553.696; C16.320.784
C535858	HEM dysplasia *(supp.)*
C537571	Jeune syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067271 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.09	Kd	81.59	nM	CHEMBL5653589
7.09	ED50	81.59	nM	CHEMBL5653589
5.24	Kd	5781	nM	CHEMBL3752910
5.24	ED50	5781	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148642: Binding affinity to human LBR incubated for 45 mins by Kinobead based pull down assay	kd	0.0816	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148642: Binding affinity to human LBR incubated for 45 mins by Kinobead based pull down assay	kd	5.7809	uM

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Resveratrol	affects cotreatment, increases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cadmium	decreases expression, decreases reaction, increases abundance, increases palmitoylation	2
Dexamethasone	increases expression, affects cotreatment	2
Hydrogen Peroxide	affects expression, decreases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
Cadmium Chloride	increases abundance, increases palmitoylation, decreases expression, decreases reaction	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
imidazopyrazole	increases expression	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
obeticholic acid	decreases expression	1
gypenoside	decreases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651684	Binding	Binding affinity to human LBR incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3A3	Abcam HEK293T LBR KO	Transformed cell line	Female
CVCL_E2AZ	HAP1 LBR (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 86 trials:

NCT	Phase	Status	Title
NCT01042158	Phase 4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	Phase 4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	Phase 4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	Phase 4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	Phase 4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	Phase 4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	Phase 4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	Phase 3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	Phase 3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	Phase 3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	Phase 3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT06716606	Phase 3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	Phase 3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00004357	Phase 2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	Phase 2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	Phase 2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	Phase 2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	Phase 2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	Phase 2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	Phase 2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	Phase 2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01093911	Phase 1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	Phase 1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	Phase 1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	Phase 1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	Phase 1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT01424033	Phase 2/3	TERMINATED	A Clinical Trial for CTD-ILD Treatment
NCT04915482	Phase 2/3	UNKNOWN	TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT06574581	Phase 1/2	RECRUITING	ADSCs Therapy in Patients With CTD-ILD
NCT00001330	Not specified	COMPLETED	Study of Silicone-Associated Connective Tissue Diseases
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00001978	Not specified	TERMINATED	Determination of Kidney Function
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease
NCT00341679	Not specified	COMPLETED	Studies of the Natural History and Pathogenesis of Autoimmune/Connective Tissue Diseases
NCT00470327	Not specified	RECRUITING	A Study of the Natural Progression of Interstitial Lung Disease (ILD)
NCT00491309	Not specified	UNKNOWN	Exercise and Respiratory Therapy in Patients With Rheumatoid Arthritis / Collagenosis and Pulmonary Hypertension
NCT00522002	Not specified	COMPLETED	CLUE Study: Connective Tissue Disease Leg Ulcer Etiology Study
NCT00802607	Not specified	TERMINATED	Collection of Tissue Specimens for Analysis and Establishment of Cell Cultures
NCT01208792	Not specified	COMPLETED	Auto-immunity and Pulmonary Arterial Hypertension
NCT01379118	Not specified	COMPLETED	Comparison of Clinical Outcomes and Performance of Total Knee Replacement Patients Before and After Surgery
NCT01387035	Not specified	UNKNOWN	Early Diagnosis of Pulmonary Hypertension in Patients With Inflammatory Rheumatic Connective Tissue Diseases
NCT01656278	Not specified	COMPLETED	An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis
NCT01809574	Not specified	UNKNOWN	The Role of Rheumatological Evaluation in the Management of Patients With Interstitial Lung Disease
NCT02768259	Not specified	UNKNOWN	Prevalence of Pulmonary Arterial Hypertension in Patients With Connective Tissue Diseases in Egyptian Patients
NCT03214263	Not specified	UNKNOWN	Identification of New Biomarkers to Promote Personalized Treatment of Patients With Inflammatory Rheumatic Diseases
NCT03446339	Not specified	UNKNOWN	Pulmonary Hypertension Screening for Rheumatology Patients (SOPHIE)
NCT03494036	Not specified	COMPLETED	Effect of Synbiotic on Immune Response, Gut Permeability and Microbiota in Patient With Connective Tissue Disease
NCT03565601	Not specified	UNKNOWN	Prognostic Value of Anti-Ro52 Antibodies in Connective Tissue Diseases (a-Ro52)
NCT03847753	Not specified	COMPLETED	Exploring the Comorbidity Between Mental Disorders and General Medical Conditions
NCT04095351	Not specified	RECRUITING	Connective Tissue Diseases and Lung Manifestations
NCT04171362	Not specified	COMPLETED	The Effect of Connective Tissue Massage in Patients With Migraine
NCT04297371	Not specified	COMPLETED	Early Detection of Cardiac Impairment and Prediction of RV Hypertrophy in Patients With CTD
NCT04398628	Not specified	RECRUITING	ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
NCT04428957	Not specified	UNKNOWN	Telemonitoring of Treatment Effects in Connective Tissue Disease-associated Interstitial Lung Disease (TEL-CTD-ILD)
NCT04582292	Not specified	UNKNOWN	Laryngeal Manifestations of Connective Tissue Diseases
NCT04664478	Not specified	COMPLETED	Gene First Approach to Connective Tissue Disease
NCT04702295	Not specified	UNKNOWN	ERN ReCONNET Study on COVID-19 Vaccination in Rare and Complex Connective Tissue Disease (VACCINATE)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LBR across ~30M SureChEMBL compounds — explore on Sugi Predict.