LDB1

Summary

LDB1 (LIM domain binding 1, HGNC:6532) is a protein-coding gene on chromosome 10q24.32, encoding LIM domain-binding protein 1 (Q86U70). Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors.

Enables LIM domain binding activity; RNA polymerase II-specific DNA-binding transcription factor binding activity; and enzyme binding activity. Involved in negative regulation of DNA-templated transcription and positive regulation of transcription by RNA polymerase II. Located in chromatin. Part of beta-catenin-TCF complex.

Source: NCBI Gene 8861 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital hydrocephalus (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 47 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_001113407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6532
Approved symbol	LDB1
Name	LIM domain binding 1
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	NLI, CLIM2
Ensembl gene	ENSG00000198728
Ensembl biotype	protein_coding
OMIM	603451
Entrez	8861

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361198, ENST00000425280, ENST00000461873, ENST00000673968

RefSeq mRNA: 3 — MANE Select: NM_001113407 NM_001113407, NM_001321612, NM_003893

CCDS: CCDS44472, CCDS7528, CCDS91327

Canonical transcript exons

ENST00000673968 — 11 exons

Exon	Start	End
ENSE00000987601	102110529	102110701
ENSE00000987602	102109921	102110043
ENSE00000987603	102109600	102109683
ENSE00000987604	102109384	102109507
ENSE00000987605	102109029	102109177
ENSE00001451519	102106489	102108323
ENSE00001835858	102120086	102120368
ENSE00003473743	102111434	102111536
ENSE00003560015	102111256	102111300
ENSE00003568764	102110869	102110971
ENSE00003626159	102111069	102111144

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.4361 / max 572.9398, expressed in 1825 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111132	17.6757	1789
111129	8.0103	1649
111131	6.6652	1444
111134	5.9589	1711
111133	2.7120	1319
111127	1.9284	1045
111135	0.7665	419
111136	0.6232	281
111138	0.5640	321
111126	0.2252	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.62	gold quality
ganglionic eminence	UBERON:0004023	98.34	gold quality
left ovary	UBERON:0002119	98.26	gold quality
skin of leg	UBERON:0001511	97.95	gold quality
mucosa of stomach	UBERON:0001199	97.93	gold quality
skin of abdomen	UBERON:0001416	97.92	gold quality
right ovary	UBERON:0002118	97.89	gold quality
endocervix	UBERON:0000458	97.81	gold quality
sural nerve	UBERON:0015488	97.80	gold quality
cortical plate	UBERON:0005343	97.66	gold quality
body of uterus	UBERON:0009853	97.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.20	gold quality
ectocervix	UBERON:0012249	97.17	gold quality
lower esophagus	UBERON:0013473	97.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.02	gold quality
stromal cell of endometrium	CL:0002255	96.86	gold quality
granulocyte	CL:0000094	96.84	gold quality
adenohypophysis	UBERON:0002196	96.72	gold quality
left uterine tube	UBERON:0001303	96.41	gold quality
apex of heart	UBERON:0002098	96.23	gold quality
right lobe of thyroid gland	UBERON:0001119	96.19	gold quality
left lobe of thyroid gland	UBERON:0001120	96.10	gold quality
metanephros cortex	UBERON:0010533	96.08	gold quality
minor salivary gland	UBERON:0001830	96.03	gold quality
right coronary artery	UBERON:0001625	95.91	gold quality
gall bladder	UBERON:0002110	95.74	gold quality
ventricular zone	UBERON:0003053	95.72	gold quality
lower esophagus mucosa	UBERON:0035834	95.67	gold quality
tibial nerve	UBERON:0001323	95.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	1457.31
E-HCAD-6	yes	43.86
E-ANND-3	yes	6.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

141 targeting LDB1, 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-6798-5P	100.00	65.77	699
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
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-548AN	99.97	70.91	2817
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 18)

• 1H, 15N and 13C assignments of FLIN4, an intramolecular LMO4:ldb1 complex (PMID:12153047)
• Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development (PMID:12381786)
• characterize the assembly of a five-component complex containing TAL1, LMO2, Ldb1, E12, and DNA. The bHLH domains of TAL1 and E12 alone primarily formed helical homodimers, but together formed heterodimers, to which LMO2 bound with high affinity (PMID:17910069)
• Although the LIM interaction domain of Ldb1 (Ldb1(LID)) and Isl1(LBD) share low levels of sequence homology, X-ray and NMR structures reveal that they bind Lhx3 in an identical manner, that is, Isl1(LBD) mimics Ldb1(LID). (PMID:18583962)
• Expression of LDB1 (LIM-domain-binding 1) protein in which Lys134 is replaced with arginine leads to enhanced expression of the mutant protein compared with the wild-type protein. (PMID:20423330)
• These studies are consistent with a model in which TIF1gamma acts to ubiquitinate LDB1 leading to degradation of LDB1 and changes in transcription of LDB1-dependent promoters. (PMID:20447379)
• We investigated NLI (Ldb1 homolog) complex occupancy and chromatin conformation of the beta-globin locus in human erythroid cells. (PMID:22010104)
• In t(8;21) leukemia cells, LDB1 functions as a component of the stable AML1-ETO-containing transcription factor complex (AETFC). The AETFC components cooperatively regulate gene expression and contribute to leukemogenesis. (PMID:23812588)
• Clim2, in a complex with LMO4, supports mammary stem cells by directly targeting the Fgfr2 promoter in basal cells to increase its expression (PMID:25079073)
• SSBP3 Interacts With Islet-1 and Ldb1 to Impact Pancreatic beta-Cell Target Genes (PMID:26495868)
• Alanine scanning mutagenesis of the LIM interaction domain of LDB1 revealed a discrete motif, R(320)LITR, required for LMO2 binding. (PMID:26598604)
• Data indicate that LIM-domain-binding protein 1 (LDB1) has a strong role in colorectal cancer (CRC) progression. (PMID:27713177)
• LDB1 maintains the terminally differentiated state of beta cells and is a component of active enhancers in both murine and human islets. (PMID:27941246)
• LDB1 dimerization supports long-range connections between enhancers and genes involved in erythropoiesis, including the beta-globin genes. Single-stranded DNA binding proteins (SSBPs) interact specifically with the LDB/Chip conserved domain (LCCD) of LDB proteins and stabilize LDBs by preventing their proteasomal degradation, thus promoting their functions in gene regulation. (PMID:31892537)
• LDB1 Enforces Stability on Direct and Indirect Oncoprotein Partners in Leukemia. (PMID:32229578)
• The Ldb1 transcriptional co-regulator is required for establishment and maintenance of the pancreatic endocrine lineage. (PMID:35881062)
• LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1. (PMID:37573405)
• An intricate regulatory circuit between FLI1 and GATA1/GATA2/LDB1/ERG dictates erythroid vs. megakaryocytic differentiation. (PMID:38695236)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ldb1a	ENSDARG00000010137
danio_rerio	ldb1b	ENSDARG00000103158
mus_musculus	Ldb1	ENSMUSG00000025223
rattus_norvegicus	Ldb1	ENSRNOG00000018468
drosophila_melanogaster	Chi	FBGN0013764
caenorhabditis_elegans		WBGENE00002261

Paralogs (1): LDB2 (ENSG00000169744)

Protein

Protein identifiers

LIM domain-binding protein 1 — Q86U70 (reviewed: Q86U70)

Alternative names: Carboxyl-terminal LIM domain-binding protein 2, LIM domain-binding factor CLIM2, Nuclear LIM interactor

All UniProt accessions (2): Q86U70, A0A6E1WJ75

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state.

Subunit / interactions. Interacts with ESR1. Forms homodimers and heterodimers. Interacts with and activates LHX1/LIM1. Interacts with the LIM domains of ISL1 and LMO2. Can assemble in a complex with LMO2 and TAL1/SCL but does not interact with TAL1/SCL directly. Strongly interacts with the LIM2 domain of LMX1A and more weakly with the LIM1 domain. Homodimerization is not required for, and does not effect, LMX1A-binding. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with LHX6 and LHX9. At neuronal promoters, forms a complex with LHX3 involved in the specification of interneurons, in motor neurons, it is displaced by ISL1 to form a ternary complex in which ISL1 contacts both LHX3 and LDB1. Interacts with SLK; leading to negatively regulate SLK kinase activity. Interacts with YWHAZ. Interacts with PRDM1/BLIMP1. Interacts with LMO4. Interacts with RLIM/RNF12; the interaction inhibits the ubiquitination of LMO proteins.

Subcellular location. Nucleus.

Tissue specificity. Expressed in a wide range of adult tissues including brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes.

Post-translational modifications. Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome.

Domain organisation. The dimerization domain is located in the N-terminus.

Miscellaneous. Acts as a negative coregulator of ESR1-mediated transcription in breast cancer cells. Due to intron retention. Lacks LIM-binding domain.

Similarity. Belongs to the LDB family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86U70-1	1	yes
Q86U70-3	2, b
Q86U70-2	3, a

RefSeq proteins (3): NP_001106878, NP_001308541, NP_003884 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029005	LIM-bd/SEUSS	Family
IPR041363	LID	Domain

Pfam: PF01803, PF17916

UniProt features (40 total): strand 13, helix 9, modified residue 4, splice variant 3, turn 3, region of interest 2, initiator methionine 1, chain 1, sequence variant 1, mutagenesis site 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7OB5	X-RAY DIFFRACTION	1.8
7OB8	X-RAY DIFFRACTION	1.8
9F5B	X-RAY DIFFRACTION	1.8
2XJY	X-RAY DIFFRACTION	2.4
8HIB	X-RAY DIFFRACTION	2.45
2XJZ	X-RAY DIFFRACTION	2.8
2YPA	X-RAY DIFFRACTION	2.8
6TYD	X-RAY DIFFRACTION	2.8
8SSU	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86U70-F1	72.04	0.45

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 (4): 2, 61, 265, 302

Mutagenesis-validated functional residues (1):

Position	Phenotype
245–249	abolishes interaction with esr1.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9733709	Cardiogenesis
R-HSA-9752946	Expression and translocation of olfactory receptors
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-376176	Signaling by ROBO receptors
R-HSA-381753	Olfactory Signaling Pathway
R-HSA-422475	Axon guidance
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9675108	Nervous system development
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 300 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_HEMOGLOBIN_METABOLIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_MYELOID_CELL_HOMEOSTASIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GCANCTGNY_MYOD_Q6, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_CEREBELLAR_PURKINJE_CELL_LAYER_FORMATION

GO Biological Process (24): negative regulation of transcription by RNA polymerase II (GO:0000122), transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery (GO:0000972), gastrulation with mouth forming second (GO:0001702), hair follicle development (GO:0001942), transcription by RNA polymerase II (GO:0006366), cell adhesion (GO:0007155), nervous system development (GO:0007399), anterior/posterior axis specification (GO:0009948), epithelial structure maintenance (GO:0010669), Wnt signaling pathway (GO:0016055), cerebellar Purkinje cell differentiation (GO:0021702), neuron differentiation (GO:0030182), regulation of cell migration (GO:0030334), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), somatic stem cell population maintenance (GO:0035019), regulation of kinase activity (GO:0043549), negative regulation of erythrocyte differentiation (GO:0045647), positive regulation of cell adhesion (GO:0045785), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of hemoglobin biosynthetic process (GO:0046985), regulation of focal adhesion assembly (GO:0051893), cerebellum development (GO:0021549), head development (GO:0060322)

GO Molecular Function (11): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), enzyme binding (GO:0019899), LIM domain binding (GO:0030274), protein homodimerization activity (GO:0042803), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cell leading edge (GO:0031252), protein-containing complex (GO:0032991), beta-catenin-TCF complex (GO:1990907), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Developmental Biology	2
Transcriptional regulation by RUNX1	1
Signaling by ROBO receptors	1
Olfactory Signaling Pathway	1
RNA Polymerase II Transcription	1
Axon guidance	1
Sensory Perception	1
Nervous system development	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
binding	2
protein binding	2
negative regulation of DNA-templated transcription	1
chromosome organization	1
gastrulation	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
cellular process	1
system development	1
axis specification	1
anterior/posterior pattern specification	1
tissue homeostasis	1
cell surface receptor signaling pathway	1
cell differentiation in hindbrain	1
cerebellar Purkinje cell layer formation	1
central nervous system neuron differentiation	1
cell differentiation	1
generation of neurons	1
cell migration	1
regulation of cell motility	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
stem cell population maintenance	1
kinase activity	1
regulation of phosphorylation	1
regulation of transferase activity	1
erythrocyte differentiation	1
negative regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1

Protein interactions and networks

STRING

1464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDB1	LMO2	P25791	999
LDB1	GATA1	P15976	996
LDB1	TAL1	P17542	995
LDB1	LHX3	Q9UBR4	995
LDB1	TCF3	P15883	993
LDB1	GATA2	P23769	988
LDB1	ISL1	P20663	987
LDB1	CBFA2T3	O75081	982
LDB1	LMO1	P25800	973
LDB1	LYL1	P12980	967
LDB1	ZFPM1	Q8IX07	938
LDB1	LHX2	P50458	932
LDB1	LHX1	P48742	914
LDB1	LMO4	P61968	905
LDB1	RUNX1	Q01196	888

IntAct

150 interactions, top by confidence:

A	B	Type	Score
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
LDB1	LHX6	psi-mi:“MI:0915”(physical association)	0.760
LHX6	LDB1	psi-mi:“MI:0915”(physical association)	0.760
LMX1B	LDB1	psi-mi:“MI:0915”(physical association)	0.750
LDB1	LMX1B	psi-mi:“MI:0915”(physical association)	0.750
LMO2	LDB1	psi-mi:“MI:0915”(physical association)	0.740
SSBP3	LDB1	psi-mi:“MI:0915”(physical association)	0.740
LDB1	LMO2	psi-mi:“MI:0915”(physical association)	0.740
SSBP3	LMX1B	psi-mi:“MI:0914”(association)	0.740
PYGO1	BCL9	psi-mi:“MI:0914”(association)	0.700
LDB1	LHX8	psi-mi:“MI:0915”(physical association)	0.690
LHX8	LDB1	psi-mi:“MI:0915”(physical association)	0.690
LHX8	LDB1	psi-mi:“MI:0914”(association)	0.690
TAL1	TCF4	psi-mi:“MI:0914”(association)	0.690
SYNGAP1	LDB1	psi-mi:“MI:0915”(physical association)	0.680
LDB1	SYNGAP1	psi-mi:“MI:0915”(physical association)	0.680
LMO1	LDB1	psi-mi:“MI:0915”(physical association)	0.670
LDB1	LMO4	psi-mi:“MI:0915”(physical association)	0.670
LDB1	LMO1	psi-mi:“MI:0915”(physical association)	0.670
LMO4	LDB1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (231): LDB1 (Two-hybrid), LDB1 (Two-hybrid), LDB1 (Two-hybrid), LDB1 (Two-hybrid), SSBP3 (Two-hybrid), LHX6 (Two-hybrid), LHX8 (Two-hybrid), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), LDB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q7JC00, A2RRV3, A2YAA5, A3B9A0, A8MQL1, B2C6R6, B5DE09, F4J077, F4JT98, F4JYG0, O22873, O42252, O48847, O73715, P70060, P70662, P93022, Q04088, Q0D3J9, Q0D5G4, Q0D9R7, Q0WPK4, Q0WVM7, Q10M00, Q4V3C1, Q64M78, Q69IL4, Q6GP15, Q6Z2W3, Q7XYY2, Q86U70, Q8RYC8, Q8W234, Q924H2, Q940A7, Q940D0, Q940I0, Q94BP0, Q94C98, Q96RN5

Diamond homologs: G5EEL0, O42252, O43679, O55203, O73715, P70060, P70662, Q1EQW7, Q6NVL6, Q86U70, Q9W676

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
LDB1	“up-regulates activity”	LHX2	binding
RLIM	“down-regulates quantity by destabilization”	LDB1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Deactivation of the beta-catenin transactivating complex	7	23.0×	9e-06
Gastrulation	5	18.3×	1e-03
MITF-M-dependent gene expression	5	12.8×	3e-03
TCF dependent signaling in response to WNT	6	9.9×	3e-03
MITF-M-regulated melanocyte development	6	9.7×	3e-03
Signaling by WNT	6	9.5×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	6	41.7×	7e-07
negative regulation of neuron differentiation	5	13.5×	2e-03
somatic stem cell population maintenance	5	12.3×	2e-03
anatomical structure morphogenesis	8	11.0×	6e-05
neuron differentiation	11	10.9×	7e-07
transcription by RNA polymerase II	13	9.1×	4e-07
chromatin remodeling	9	6.5×	7e-04
brain development	7	5.5×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — MBL, PAST.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1329 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102109027:A:AC	donor_gain	1.0000
10:102109028:C:CC	donor_gain	1.0000
10:102109028:CAGGT:C	donor_gain	1.0000
10:102109030:GGTAC:G	donor_loss	1.0000
10:102109031:GTACC:G	donor_loss	1.0000
10:102109032:TA:T	donor_loss	1.0000
10:102109033:A:C	donor_loss	1.0000
10:102109034:C:A	donor_loss	1.0000
10:102109034:CCTGG:C	donor_gain	1.0000
10:102109173:CTCCG:C	acceptor_gain	1.0000
10:102109175:CCG:C	acceptor_gain	1.0000
10:102109176:CG:C	acceptor_gain	1.0000
10:102109176:CGCTG:C	acceptor_gain	1.0000
10:102109178:C:CC	acceptor_gain	1.0000
10:102109185:G:T	acceptor_gain	1.0000
10:102109503:CAGAG:C	acceptor_gain	1.0000
10:102109504:AGAG:A	acceptor_gain	1.0000
10:102109505:GAG:G	acceptor_gain	1.0000
10:102109506:AG:A	acceptor_gain	1.0000
10:102109506:AGCTA:A	acceptor_loss	1.0000
10:102109507:GC:G	acceptor_loss	1.0000
10:102109508:C:CC	acceptor_gain	1.0000
10:102109508:CT:C	acceptor_loss	1.0000
10:102109594:ACT:A	donor_loss	1.0000
10:102109595:CTC:C	donor_loss	1.0000
10:102109596:TCA:T	donor_loss	1.0000
10:102109597:CA:C	donor_loss	1.0000
10:102109598:A:AC	donor_gain	1.0000
10:102109599:C:CA	donor_gain	1.0000
10:102109599:CT:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000022469 (10:102114448 T>G), RS1000151858 (10:102111942 T>C,G), RS1000206814 (10:102120435 GC>G,GCC), RS1000435263 (10:102118944 T>C,G), RS1000620332 (10:102113149 T>C), RS1000635849 (10:102119367 T>C), RS1000659705 (10:102107319 C>A,T), RS1000752231 (10:102113483 G>A,T), RS1000816999 (10:102107126 C>T), RS1000909798 (10:102113510 C>A), RS1001225510 (10:102113059 A>G), RS1001290074 (10:102102143 T>C), RS1001301367 (10:102117680 C>T), RS1001315188 (10:102101930 C>A,T), RS1001416750 (10:102117480 G>T)

Disease associations

OMIM: gene MIM:603451 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital hydrocephalus	Strong	Autosomal dominant

Mondo (1): congenital hydrocephalus (MONDO:0016349)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005316_349	Intelligence (MTAG)	1.000000e-09
GCST006269_820	General cognitive ability	1.000000e-08
GCST007269_114	Pulse pressure	2.000000e-10
GCST90002396_493	Mean reticulocyte volume	4.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0005763	pulse pressure measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	affects splicing	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1VR	Abcam HeLa LDB1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06664372	Not specified	NOT_YET_RECRUITING	Insertion of Frontal Ventricular Catheter of VP Shunt in Congenital Hydrocephalus Guided by Trans Fontanelle Ultrasound