LBX2

Summary

LBX2 (ladybird homeobox 2, HGNC:15525) is a protein-coding gene on chromosome 2p13.1, encoding Transcription factor LBX2 (Q6XYB7). Transcription factor.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including positive regulation of convergent extension involved in gastrulation; positive regulation of non-canonical Wnt signaling pathway; and regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 85474 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001282430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15525
Approved symbol	LBX2
Name	ladybird homeobox 2
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000179528
Ensembl biotype	protein_coding
OMIM	607164
Entrez	85474

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000341396, ENST00000377566, ENST00000460508, ENST00000479098, ENST00000550249, ENST00000618878

RefSeq mRNA: 2 — MANE Select: NM_001282430 NM_001009812, NM_001282430

CCDS: CCDS33228, CCDS62938

Canonical transcript exons

ENST00000377566 — 2 exons

Exon	Start	End
ENSE00001220187	74497517	74498318
ENSE00001474366	74499333	74499603

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 86.20.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4054 / max 25.0981, expressed in 794 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29221	1.0842	650
29219	0.1717	69
29220	0.1495	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	86.20	gold quality
liver	UBERON:0002107	78.93	gold quality
duodenum	UBERON:0002114	76.99	gold quality
bone marrow cell	CL:0002092	73.96	gold quality
mucosa of transverse colon	UBERON:0004991	73.84	gold quality
stromal cell of endometrium	CL:0002255	73.42	gold quality
gall bladder	UBERON:0002110	69.71	gold quality
small intestine	UBERON:0002108	68.87	gold quality
colonic epithelium	UBERON:0000397	68.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.41	gold quality
granulocyte	CL:0000094	66.91	gold quality
blood	UBERON:0000178	66.01	gold quality
bone marrow	UBERON:0002371	65.11	gold quality
minor salivary gland	UBERON:0001830	64.86	gold quality
body of stomach	UBERON:0001161	64.81	gold quality
thoracic mammary gland	UBERON:0005200	64.52	gold quality
omental fat pad	UBERON:0010414	64.45	gold quality
stomach	UBERON:0000945	64.22	gold quality
metanephros cortex	UBERON:0010533	64.17	gold quality
placenta	UBERON:0001987	64.11	gold quality
adult mammalian kidney	UBERON:0000082	64.05	gold quality
tibial nerve	UBERON:0001323	63.76	gold quality
transverse colon	UBERON:0001157	63.74	gold quality
saliva-secreting gland	UBERON:0001044	63.66	gold quality
adipose tissue	UBERON:0001013	63.53	gold quality
apex of heart	UBERON:0002098	63.34	gold quality
monocyte	CL:0000576	63.33	gold quality
cortex of kidney	UBERON:0001225	63.14	gold quality
fundus of stomach	UBERON:0001160	63.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.78

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0699.1	LBX2	NK
MA0699.2	LBX2	NK

JASPAR matrix evidence (PMIDs): PMID:18585360

miRNA regulators (miRDB)

28 targeting LBX2, 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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-6781-5P	94.61	59.49	155

Literature-anchored findings (GeneRIF, showing 4)

• LBX2 was identified as a pathogenic gene in Chinese patients with atrial septal defect. (PMID:29669692)
• LncRNA LBX2-AS1 facilitates abdominal aortic aneurysm through miR-4685-5p/LBX2 feedback loop. (PMID:32559617)
• Identification of LBX2 as a novel causal gene of lung adenocarcinoma. (PMID:32567804)
• Histone modification-linked prognostic model for ovarian cancer reveals LBX2 as a novel growth promoter. (PMID:38520216)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	lbx1a	ENSDARG00000018321
danio_rerio	lbx1b	ENSDARG00000018611
danio_rerio	lbx2	ENSDARG00000025131
mus_musculus	Lbx2	ENSMUSG00000034968
rattus_norvegicus	Lbx2	ENSRNOG00000008466
drosophila_melanogaster	lbl	FBGN0008651
drosophila_melanogaster	lbe	FBGN0011278

Paralogs (1): LBX1 (ENSG00000138136)

Protein

Protein identifiers

Transcription factor LBX2 — Q6XYB7 (reviewed: Q6XYB7)

Alternative names: Ladybird homeobox 2, Ladybird homeobox protein homolog 2

All UniProt accessions (2): Q6XYB7, G3V218

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6XYB7-1	1	yes
Q6XYB7-2	2

RefSeq proteins (2): NP_001009812, NP_001269359* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR051892	LBX_TF	Family

Pfam: PF00046

UniProt features (9 total): region of interest 3, sequence variant 3, chain 1, DNA-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6XYB7-F1	75.67	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_GASTRULATION, GOBP_CONVERGENT_EXTENSION, GOBP_EMBRYO_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_POSITIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_TISSUE_MORPHOGENESIS

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), muscle cell differentiation (GO:0042692), positive regulation of convergent extension involved in gastrulation (GO:1904105), positive regulation of non-canonical Wnt signaling pathway (GO:2000052)

GO Molecular Function (4): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cell differentiation	1
muscle structure development	1
convergent extension involved in gastrulation	1
regulation of convergent extension involved in gastrulation	1
positive regulation of morphogenesis of an epithelium	1
positive regulation of Wnt signaling pathway	1
non-canonical Wnt signaling pathway	1
regulation of non-canonical Wnt signaling pathway	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LBX2	WDR54	Q9H977	445
LBX2	CCDC142	Q17RM4	436
LBX2	ZNF26	P17031	370
LBX2	C2orf81	A6NN90	370
LBX2	M1AP	Q8TC57	367
LBX2	C8orf58	Q8NAV2	355
LBX2	SHISAL2A	Q6UWV7	348
LBX2	INO80B	Q9C086	336
LBX2	TTC31	Q49AM3	320
LBX2	PCDHB12	Q9Y5F1	314
LBX2	ENTPD5	O75356	302
LBX2	EVA1B	Q9NVM1	296
LBX2	MOGS	Q13724	296
LBX2	SACK1B	Q5T0W9	293
LBX2	FOXL1	Q12952	288

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MYC		psi-mi:“MI:0914”(association)	0.350
LBX2	GGPS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): LBX2 (Two-hybrid), GFAP (Affinity Capture-MS), GGPS1 (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), PREPL (Affinity Capture-MS), TRPC4AP (Affinity Capture-MS), LBX2 (Protein-peptide)

ESM2 similar proteins: A1YEV8, A1YF08, A1YG25, A1YG85, A2RU54, A2T711, A2T756, A8MTQ0, O14813, O15522, O35160, O35602, O43763, O70218, P28360, P42580, P43687, P50223, P52945, P52946, P52947, P70118, P70354, P81062, Q06348, Q2VL79, Q2VL84, Q2VL85, Q2VL87, Q2VL88, Q61663, Q62066, Q62782, Q6XYB7, Q7YRX0, Q96IS3, Q99811, Q9DED6, Q9ER42, Q9GK08

Diamond homologs: A2X674, A2X7U1, A2X980, A2XD08, A2XDD6, A2XDK5, A2XE76, A2Y931, A2YGL9, A2YN17, A2YW03, A2YWC0, A2Z0Q0, A2Z1U1, A2Z4C4, A2Z734, A3BYC1, A5YC49, A6NJ46, D2KQB0, O23208, O35750, O35762, O60902, P0CJ65, P46600, P46601, P46602, P46603, P46604, P46665, P46667, P46668, P46897, P52950, P56407, P70390, P78426, P92953, Q00466

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

380 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74498315:CGCC:C	acceptor_gain	0.9900
2:74498317:CCCTG:C	acceptor_loss	0.9900
2:74498319:C:CG	acceptor_loss	0.9900
2:74498320:T:A	acceptor_loss	0.9900
2:74498905:C:A	donor_gain	0.9900
2:74499328:TATA:T	donor_loss	0.9900
2:74499329:ATAC:A	donor_loss	0.9900
2:74499330:TAC:T	donor_loss	0.9900
2:74499331:A:C	donor_loss	0.9900
2:74499332:C:CA	donor_loss	0.9900
2:74498319:C:CC	acceptor_gain	0.9800
2:74499320:G:A	donor_gain	0.9800
2:74498314:CCGCC:C	acceptor_gain	0.9700
2:74498315:CGCCC:C	acceptor_gain	0.9700
2:74498317:CC:C	acceptor_gain	0.9700
2:74498318:CC:C	acceptor_gain	0.9700
2:74499379:A:AC	donor_gain	0.9700
2:74499380:C:CC	donor_gain	0.9700
2:74498904:C:CA	donor_gain	0.9600
2:74498961:T:A	donor_gain	0.9600
2:74498993:A:AC	donor_gain	0.9500
2:74498994:C:CC	donor_gain	0.9500
2:74498316:GCC:G	acceptor_gain	0.9400
2:74498317:CCC:C	acceptor_gain	0.9400
2:74499335:T:A	donor_gain	0.9400
2:74498321:G:C	acceptor_loss	0.9300
2:74498895:T:TA	donor_gain	0.9300
2:74498316:GCCCT:G	acceptor_gain	0.9200
2:74499314:G:GT	donor_gain	0.9100
2:74498994:CTCGT:C	donor_gain	0.8800

AlphaMissense

1228 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74498125:G:C	F133L	0.998
2:74498125:G:T	F133L	0.998
2:74498127:A:G	F133L	0.998
2:74498248:G:C	F92L	0.998
2:74498248:G:T	F92L	0.998
2:74498250:A:G	F92L	0.998
2:74498212:G:C	F104L	0.997
2:74498212:G:T	F104L	0.997
2:74498214:A:G	F104L	0.997
2:74498121:T:C	N135D	0.995
2:74498120:T:G	N135T	0.994
2:74498120:T:C	N135S	0.993
2:74498126:A:G	F133S	0.993
2:74498198:T:C	Y109C	0.993
2:74498249:A:C	F92C	0.993
2:74498117:C:G	R136P	0.992
2:74498128:C:A	W132C	0.992
2:74498128:C:G	W132C	0.992
2:74498119:G:C	N135K	0.991
2:74498119:G:T	N135K	0.991
2:74498126:A:C	F133C	0.991
2:74498120:T:A	N135I	0.990
2:74498122:C:A	Q134H	0.990
2:74498122:C:G	Q134H	0.990
2:74498130:A:G	W132R	0.990
2:74498130:A:T	W132R	0.990
2:74498249:A:G	F92S	0.990
2:74498127:A:C	F133V	0.989
2:74498127:A:T	F133I	0.989
2:74498199:A:G	Y109H	0.989

dbSNP variants (sampled 300 via entrez): RS1000113915 (2:74497777 CA>C,CAA), RS1000330826 (2:74499328 T>C), RS1000515517 (2:74504920 C>G,T), RS1000551059 (2:74497447 C>A), RS1001280809 (2:74498025 G>A), RS1001334672 (2:74500725 C>T), RS1001450688 (2:74500275 C>G), RS1001612185 (2:74498288 C>A), RS1002376510 (2:74501895 C>T), RS1002834612 (2:74503970 G>A), RS1003191036 (2:74499864 A>C), RS1003212764 (2:74501089 G>A), RS1003283333 (2:74500740 T>C), RS1003347033 (2:74503301 T>C), RS1003382873 (2:74503083 G>A)

Disease associations

OMIM: gene MIM:607164 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
dimethylselenide	increases expression, increases oxidation	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Niclosamide	increases expression	1
Ozone	increases expression, increases oxidation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Hydroxyl Radical	increases expression, increases oxidation	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3T5	SEES3-1V human LBX2, clone1	Embryonic stem cell	Male
CVCL_A3T6	SEES3-1V human LBX2, clone2	Embryonic stem cell	Male
CVCL_A3T7	SEES3-1V human LBX2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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