LBH

Summary

LBH (LBH regulator of Wnt signaling pathway, HGNC:29532) is a protein-coding gene on chromosome 2p23.1, encoding Protein LBH (Q53QV2). Transcriptional activator which may act in mitogen-activated protein kinase signaling pathway.

Involved in negative regulation of DNA-templated transcription; positive regulation of DNA-templated transcription; and regulation of MAPK cascade. Located in cytoplasm and nucleus. Part of protein-containing complex.

Source: NCBI Gene 81606 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_030915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29532
Approved symbol	LBH
Name	LBH regulator of Wnt signaling pathway
Location	2p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213626
Ensembl biotype	protein_coding
OMIM	611763
Entrez	81606

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000395323, ENST00000401506, ENST00000404397, ENST00000406087, ENST00000407930, ENST00000412933, ENST00000464412, ENST00000467242, ENST00000484150

RefSeq mRNA: 1 — MANE Select: NM_030915 NM_030915

CCDS: CCDS33173

Canonical transcript exons

ENST00000395323 — 3 exons

Exon	Start	End
ENSE00001642935	30257433	30260028
ENSE00001734329	30231534	30231764
ENSE00003597023	30234405	30234507

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 97.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.5816 / max 1179.7344, expressed in 1593 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19566	55.5136	1584
19573	1.1340	411
19569	0.9409	254
19567	0.8957	430
19571	0.8322	76
19574	0.4650	195
19568	0.3864	208
19572	0.2775	135
19570	0.1363	50

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	97.65	gold quality
granulocyte	CL:0000094	97.46	gold quality
blood vessel layer	UBERON:0004797	97.45	gold quality
upper lobe of left lung	UBERON:0008952	97.37	gold quality
lymph node	UBERON:0000029	97.24	gold quality
upper lobe of lung	UBERON:0008948	97.13	gold quality
ascending aorta	UBERON:0001496	97.04	gold quality
thoracic aorta	UBERON:0001515	96.99	gold quality
aorta	UBERON:0000947	96.91	gold quality
popliteal artery	UBERON:0002250	96.90	gold quality
tibial artery	UBERON:0007610	96.90	gold quality
heart left ventricle	UBERON:0002084	96.86	gold quality
visceral pleura	UBERON:0002401	96.85	gold quality
cardiac ventricle	UBERON:0002082	96.76	gold quality
apex of heart	UBERON:0002098	96.67	gold quality
calcaneal tendon	UBERON:0003701	96.33	gold quality
right coronary artery	UBERON:0001625	96.27	gold quality
lung	UBERON:0002048	96.05	gold quality
descending thoracic aorta	UBERON:0002345	95.96	gold quality
lower lobe of lung	UBERON:0008949	95.94	gold quality
spleen	UBERON:0002106	95.75	gold quality
left lobe of thyroid gland	UBERON:0001120	95.74	gold quality
left coronary artery	UBERON:0001626	95.60	gold quality
right lobe of thyroid gland	UBERON:0001119	95.53	gold quality
coronary artery	UBERON:0001621	95.46	gold quality
thyroid gland	UBERON:0002046	95.39	gold quality
gall bladder	UBERON:0002110	95.06	gold quality
right ovary	UBERON:0002118	94.91	gold quality
metanephros cortex	UBERON:0010533	94.81	gold quality
thymus	UBERON:0002370	94.68	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	589.47
E-GEOD-98556	yes	459.74
E-MTAB-10287	yes	56.27
E-CURD-122	yes	38.01
E-MTAB-7316	yes	33.00
E-HCAD-11	yes	20.25
E-MTAB-8410	yes	19.76
E-MTAB-9067	yes	11.75
E-GEOD-93593	yes	11.25
E-GEOD-134144	yes	9.88
E-CURD-112	yes	8.57
E-MTAB-9801	yes	3.86
E-MTAB-10290	no	205.63
E-GEOD-124858	no	120.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

169 targeting LBH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-12136	99.98	72.81	5713
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 15)

• LBH is implicated as a candidate gene for congenital heart disease associated with partial trisomy 2p syndrome (PMID:15958514)
• These results suggest that hLBH proteins may act as a transcriptional activator in mitogen-activated protein kinase signaling pathway to mediate cellular functions. (PMID:17390236)
• results showed that the interaction of LBH and alphaB-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21 (PMID:20587334)
• LBH is aberrantly overexpressed in mammary tumors of mouse mammary tumor virus (MMTV)-Wnt1-transgenic mice and in aggressive basal subtype human breast cancers that display Wnt/beta-catenin hyperactivation. (PMID:20606007)
• LBH normally induces NPC cell cycle arrest at the G1/S transition, and LBH can suppress the growth of transplanted NPC tumors in vivo by downregulating LMP1-mediated NF-kappaB transcriptional activity. (PMID:25557837)
• LBH is a candidate gene for synovial pathology in rheumatoid arthritis. It is regulated by growth factors and modulates cell growth in primary fibroblast-like synoviocytes. (PMID:25707478)
• The expression levels of LBH mRNA in patients with SLE were significantly decreased compared with those in normal controls (P < 0.001). No significant differences were found between LBH mRNA expression levels and SLE disease activity scores, SNP rs7579944 and rs906868. (PMID:26134586)
• Low LBH level, caused by a rheumatoid arthritis risk allele, is a risk factor for aggressive fibroblast-like synoviocyte behavior. (PMID:27159840)
• LBH was significantly down-regulated in lung cancer tissue samples and was correlated with the prognosis and clinical characteristics of lung cancer patients. Survival analysis revealed that LBH-negative expression was associated with poor overall survival of LUAD patients (P = 0.021). (PMID:29788015)
• Decreased expression of limb-bud and heart (LBH) mRNA in mononuclear leukocytes (PBMCs) might contribute to the pathogenesis of rheumatoid arthritis (RA). (PMID:30549979)
• Limb-bud and heart (LBH) inhibits cellular migration, invasion and epithelial-mesenchymal transition in nasopharyngeal carcinoma via downregulating alphaB-crystallin expression. (PMID:34000384)
• LncRNA MIR31HG Drives Oncogenicity by Inhibiting the Limb-Bud and Heart Development Gene (LBH) during Oral Carcinoma. (PMID:34445087)
• Exosomal LBH inhibits epithelial-mesenchymal transition and angiogenesis in nasopharyngeal carcinoma via downregulating VEGFA signaling. (PMID:34975330)
• Multi-cancer analysis reveals universal association of oncogenic LBH expression with DNA hypomethylation and WNT-Integrin signaling pathways. (PMID:37268816)
• Blocking LBH expression causes replication stress and sensitizes triple-negative breast cancer cells to ATR inhibitor treatment. (PMID:38297083)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lbh	ENSDARG00000111701
mus_musculus	Lbh	ENSMUSG00000024063
rattus_norvegicus	Lbh	ENSRNOG00000075058

Paralogs (1): LBHD1 (ENSG00000162194)

Protein

Protein identifiers

Protein LBH — Q53QV2 (reviewed: Q53QV2)

Alternative names: Limb bud and heart development protein homolog

All UniProt accessions (6): B5MBX5, B5MC28, B5MCM2, B5MCP4, F8WC18, Q53QV2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator which may act in mitogen-activated protein kinase signaling pathway.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in heart, and expressed at low levels in placenta, lung, skeletal muscle, kidney and liver.

Similarity. Belongs to the LBH family.

RefSeq proteins (1): NP_112177* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013294	LBH	Family
IPR038990	LBH_dom	Domain
IPR042945	LBH_dom_prot	Family

Pfam: PF15317

UniProt features (6 total): chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53QV2-F1	65.61	0.00

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 (1): 63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 291 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, PEREZ_TP63_TARGETS, GOBP_NEGATIVE_REGULATION_OF_STEM_CELL_DIFFERENTIATION, ATACCTC_MIR202, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOBP_MAMMARY_GLAND_EPITHELIAL_CELL_DIFFERENTIATION, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_STEM_CELL_DIVISION

GO Biological Process (12): negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), regulation of MAPK cascade (GO:0043408), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), mammary gland epithelial cell differentiation (GO:0060644), positive regulation of somatic stem cell population maintenance (GO:1904674), positive regulation of somatic stem cell division (GO:1904677), positive regulation of mammary stem cell proliferation (GO:2000103), negative regulation of stem cell differentiation (GO:2000737), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), mammary gland development (GO:0030879)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	2
estrogen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
MAPK cascade	1
regulation of intracellular signal transduction	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
epithelial cell differentiation	1
mammary gland epithelium development	1
somatic stem cell population maintenance	1
positive regulation of stem cell population maintenance	1
regulation of somatic stem cell population maintenance	1
somatic stem cell division	1
positive regulation of cell division	1
regulation of somatic stem cell division	1
mammary stem cell proliferation	1
positive regulation of cell population proliferation	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of mammary stem cell proliferation	1
negative regulation of cell differentiation	1
stem cell differentiation	1
regulation of stem cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
gland development	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LBH	EN1	Q05925	668
LBH	LGALS4	P56470	555
LBH	FGF8	P55075	491
LBH	CALHM5	Q8N5C1	417
LBH	SRARP	Q8NEQ6	357
LBH	CCDC192	P0DO97	354
LBH	TECPR2	O15040	347
LBH	TRMT1L	Q7Z2T5	345
LBH	SRM	P19623	314
LBH	VGLL3	A8MV65	281
LBH	NKTR	P30414	263
LBH	YPEL5	P62699	251
LBH	TMX1	Q9H3N1	251
LBH	GNS	P15586	249
LBH	CBFB	Q13951	245

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PROX1	LBH	psi-mi:“MI:0915”(physical association)	0.370
PPP3CA	RCAN1	psi-mi:“MI:0914”(association)	0.350
PPP3CB	PI4KA	psi-mi:“MI:0914”(association)	0.350
PPP3CC	PI4KA	psi-mi:“MI:0914”(association)	0.350
LBH	DHX16	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): LBH (Affinity Capture-MS), LBH (Affinity Capture-MS), LBH (Affinity Capture-MS), LBH (Affinity Capture-RNA), RIOK2 (Affinity Capture-MS), THEM4 (Affinity Capture-MS), CCDC97 (Affinity Capture-MS), HABP4 (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS), DHX16 (Affinity Capture-MS), MAP9 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), TCEB3 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), RP9 (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN25, A6ZMG4, A6ZT44, A7WQL9, B3LLZ8, C7GWA2, C8ZEW0, O12161, O54842, O59835, O96447, P05860, P0CT86, P0DTH7, P11191, P11192, P17285, P17753, P18038, P21017, P21740, P24360, P29887, P30637, P33868, P41321, P41462, P42939, P46583, P53329, P54827, P61248, P79943, Q03937, Q04438, Q2TBV0, Q2V2P0, Q38664, Q53QV2, Q5BL73

Diamond homologs: A0A0U1RRK4, A5PJU8, Q53QV2, Q5M7L2, Q5RD13, Q5ZM46, Q91715, Q9CX60

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:30257536:T:C	L78P	1.000
2:30257541:T:A	W80R	1.000
2:30257541:T:C	W80R	1.000
2:30257543:G:C	W80C	1.000
2:30257543:G:T	W80C	1.000
2:30257494:T:A	I64K	0.999
2:30257536:T:A	L78H	0.999
2:30257487:C:A	P62T	0.998
2:30257487:C:T	P62S	0.998
2:30257494:T:G	I64R	0.998
2:30257542:G:C	W80S	0.998
2:30257544:C:T	P81S	0.998
2:30257494:T:C	I64T	0.997
2:30257526:A:C	S75R	0.997
2:30257528:C:A	S75R	0.997
2:30257528:C:G	S75R	0.997
2:30257436:T:C	F45L	0.996
2:30257438:C:A	F45L	0.996
2:30257438:C:G	F45L	0.996
2:30257485:T:C	L61P	0.996
2:30257488:C:A	P62H	0.996
2:30257530:G:A	G76E	0.996
2:30257530:G:T	G76V	0.996
2:30257544:C:A	P81T	0.996
2:30257485:T:A	L61Q	0.995
2:30257488:C:G	P62R	0.995
2:30257541:T:G	W80G	0.995
2:30257490:T:C	S63P	0.994
2:30257529:G:A	G76R	0.994
2:30257529:G:C	G76R	0.994

dbSNP variants (sampled 300 via entrez): RS1000034126 (2:30233416 T>C), RS1000130248 (2:30235633 G>A), RS1000172708 (2:30258542 C>T), RS1000347231 (2:30252991 G>A,T), RS1000383568 (2:30253280 A>G), RS1000496290 (2:30231354 C>T), RS1000499194 (2:30230135 T>G), RS1000500711 (2:30235420 A>G), RS1000608327 (2:30258822 C>T), RS1000610835 (2:30231541 G>A), RS1000738728 (2:30257037 G>C), RS1000873168 (2:30249174 T>C), RS1000897611 (2:30246740 T>C), RS1000960972 (2:30247339 A>G), RS1001013248 (2:30247033 C>G,T)

Disease associations

OMIM: gene MIM:611763 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	5
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	3
Tretinoin	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	decreases expression, increases expression	3
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Lipopolysaccharides	decreases expression, affects expression, affects response to substance, increases expression, affects cotreatment	2
Silicon Dioxide	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
gallium arsenide	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
tebuconazole	decreases expression	1
abrine	decreases expression	1
quinocetone	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.