LPP

Summary

LPP (LIM domain containing preferred translocation partner in lipoma, HGNC:6679) is a protein-coding gene on chromosome 3q27.3-q28, encoding Lipoma-preferred partner (Q93052). May play a structural role at sites of cell adhesion in maintaining cell shape and motility.

This gene encodes a member of a subfamily of LIM domain proteins that are characterized by an N-terminal proline-rich region and three C-terminal LIM domains. The encoded protein localizes to the cell periphery in focal adhesions and may be involved in cell-cell adhesion and cell motility. This protein also shuttles through the nucleus and may function as a transcriptional co-activator. This gene is located at the junction of certain disease-related chromosomal translocations, which result in the expression of chimeric proteins that may promote tumor growth. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4026 — RefSeq curated summary.

At a glance

• GWAS associations: 117
• Clinical variants (ClinVar): 213 total — 2 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001375462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6679
Approved symbol	LPP
Name	LIM domain containing preferred translocation partner in lipoma
Location	3q27.3-q28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145012
Ensembl biotype	protein_coding
OMIM	600700
Entrez	4026

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 83 protein_coding, 9 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000414139, ENST00000415906, ENST00000416784, ENST00000420410, ENST00000426274, ENST00000430340, ENST00000443217, ENST00000448637, ENST00000454789, ENST00000457242, ENST00000459897, ENST00000462758, ENST00000471917, ENST00000474472, ENST00000483938, ENST00000484468, ENST00000487347, ENST00000494044, ENST00000494233, ENST00000617246, ENST00000618621, ENST00000710845, ENST00000710846, ENST00000854486, ENST00000854487, ENST00000854488, ENST00000854489, ENST00000854490, ENST00000854491, ENST00000854492, ENST00000854493, ENST00000854494, ENST00000854495, ENST00000854496, ENST00000854497, ENST00000854498, ENST00000854499, ENST00000854500, ENST00000854501, ENST00000854502, ENST00000854503, ENST00000854504, ENST00000854505, ENST00000854506, ENST00000854507, ENST00000854508, ENST00000854509, ENST00000854510, ENST00000854511, ENST00000854512, ENST00000854513, ENST00000854514, ENST00000854515, ENST00000854516, ENST00000854517, ENST00000854518, ENST00000854519, ENST00000854520, ENST00000854521, ENST00000854522, ENST00000854523, ENST00000854524, ENST00000854525, ENST00000854526, ENST00000854527, ENST00000854528, ENST00000854529, ENST00000854530, ENST00000854531, ENST00000854532, ENST00000854533, ENST00000854534, ENST00000949728, ENST00000949729, ENST00000949730, ENST00000949731, ENST00000949732, ENST00000949733, ENST00000949734, ENST00000949735, ENST00000949736, ENST00000949737, ENST00000949738, ENST00000949739, ENST00000949740, ENST00000949741, ENST00000949742, ENST00000949743, ENST00000949744, ENST00000949745, ENST00000949746, ENST00000949747, ENST00000949748

RefSeq mRNA: 35 — MANE Select: NM_001375462 NM_001167671, NM_001167672, NM_001375455, NM_001375456, NM_001375457, NM_001375458, NM_001375459, NM_001375460, NM_001375461, NM_001375462, NM_001375463, NM_001375464, NM_001375465, NM_001387663, NM_001387664, NM_001387665, NM_001387666, NM_001387667, NM_001387668, NM_001387669, NM_001387670, NM_001387671, NM_001387672, NM_001387673, NM_001387674, NM_001387675, NM_001387676, NM_001387677, NM_001387678, NM_001387679, NM_001387680, NM_001387681, NM_001387682, NM_001387683, NM_005578

CCDS: CCDS3291

Canonical transcript exons

ENST00000617246 — 12 exons

Exon	Start	End
ENSE00001270076	188406112	188406313
ENSE00001512045	188225405	188225527
ENSE00001631837	188341663	188341719
ENSE00003464319	188484592	188484704
ENSE00003583703	188609161	188609844
ENSE00003601730	188524665	188524787
ENSE00003920791	188154157	188154252
ENSE00004013829	188708267	188708393
ENSE00004013830	188872643	188872763
ENSE00004013831	188874351	188890671
ENSE00004013832	188866200	188866378
ENSE00004013833	188760113	188760282

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9615 / max 1376.0146, expressed in 1740 samples.

FANTOM5 promoters (35 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40415	15.5373	1708
40424	4.8846	474
40418	3.3488	1307
40417	3.2586	1413
40423	3.0219	539
40414	0.9734	578
40409	0.9253	486
40475	0.6828	215
40449	0.6123	320
40471	0.5688	224

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.83	gold quality
urethra	UBERON:0000057	99.65	gold quality
vena cava	UBERON:0004087	99.45	gold quality
nipple	UBERON:0002030	99.44	gold quality
blood vessel layer	UBERON:0004797	99.43	gold quality
pylorus	UBERON:0001166	99.38	gold quality
cauda epididymis	UBERON:0004360	99.32	gold quality
cardia of stomach	UBERON:0001162	99.30	gold quality
seminal vesicle	UBERON:0000998	99.23	gold quality
colonic epithelium	UBERON:0000397	99.12	gold quality
superficial temporal artery	UBERON:0001614	99.04	gold quality
penis	UBERON:0000989	99.02	gold quality
pericardium	UBERON:0002407	98.94	gold quality
mammary duct	UBERON:0001765	98.20	gold quality
epithelium of mammary gland	UBERON:0003244	98.11	gold quality
synovial joint	UBERON:0002217	98.08	gold quality
popliteal artery	UBERON:0002250	98.01	gold quality
tibial artery	UBERON:0007610	98.00	gold quality
adult organism	UBERON:0007023	97.97	gold quality
lower lobe of lung	UBERON:0008949	97.92	gold quality
visceral pleura	UBERON:0002401	97.69	gold quality
cartilage tissue	UBERON:0002418	97.66	gold quality
aorta	UBERON:0000947	97.54	gold quality
renal medulla	UBERON:0000362	97.51	gold quality
superior surface of tongue	UBERON:0007371	97.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.37	gold quality
ileal mucosa	UBERON:0000331	97.36	gold quality
lower esophagus	UBERON:0013473	97.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.29	gold quality
mucosa of urinary bladder	UBERON:0001259	97.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	13104.38
E-HCAD-30	yes	2023.25
E-MTAB-10287	yes	84.94
E-GEOD-135922	yes	37.63
E-HCAD-1	yes	35.11
E-MTAB-8410	yes	29.07
E-HCAD-35	yes	27.62
E-CURD-119	yes	17.30
E-MTAB-6678	yes	11.09
E-HCAD-11	yes	10.47
E-CURD-46	yes	10.38
E-GEOD-134144	yes	8.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI3, GTF3A, ROCK1, ROCK2, TCF3, TGFB1

miRNA regulators (miRDB)

675 targeting LPP, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979

Literature-anchored findings (GeneRIF, showing 31)

• LPP contains specific domains that enable its focal adhesion and nuclear targeting capacity (PMID:12441356)
• Expression of the HMGA2-LPP fusion transcript in only 1 of 61 karyotypically normal pulmonary chondroid hamartomas. (PMID:12505264)
• LPP and Scrib proteins localize in cell-cell contacts. This interaction links Scrib to a communication pathway between cell-cell contacts and the nucleus, and implicates LPP in Scrib-associated functions (PMID:15649318)
• Translocation in chromosome 3 and 12 involves fusion of this protein with HMGA2 in pulmonary chondroid hamartoma. (PMID:16271958)
• HMGA2-LPP fusion promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains. (PMID:16375854)
• LPP appears to be a vascular smooth muscle (SMSC) differentiation marker that plays a role in regulating SMC migration. (PMID:16397143)
• LPP can shuttle between the cytoplasm and the nucleus, suggesting they may transfer information directly from the cytoskeleton or focal adhesions to the transcription machinery. (PMID:16484626)
• By manipulating LPP levels, we show that it acts to upregulate the transactivation capacity of PEA3. (PMID:16738319)
• The function of LPP and palladin is context dependent, that they play a critical role in cytoskeletal remodeling, respond to signals induced by vascular injury as well as signals that induce smooth muscle cell hypertrophy, such as angiotension II. (PMID:17322171)
• expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis. (PMID:19205907)
• Gene expression levels of bcl-6, lpp and miR-28 are different in various diffuse large B cell lymphoma cell lines. (PMID:19236753)
• LPP is a nucleocytoplasmatic shuttle protein linking focal adhesion dynamics to the transcriptional machinery. (PMID:19701494)
• haploinsufficiency of LPP may be a novel cause of conotruncal cardiac anomalies, particularly forms of tetralogy of Fallot (PMID:20949626)
• The results suggest that genomic alterations and clearly deleterious sequence changes in the LPP gene are not a common cause of esophageal atresia/tracheoesophageal fistula or VACTERL association. (PMID:22639458)
• Three polymorphisms of LPP gene were selected and replicated in additional 1132 PCOS cases and 1142 controls. Our results suggest that LPP gene might be a novel candidate for PCOS (PMID:23056290)
• interaction between LPP and alpha-actinin, an actin cross-linking protein, is necessary for TGFbeta-induced migration and invasion of ErbB2-expressing breast cancer cells. (PMID:23447672)
• Results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD. (PMID:24334606)
• 3q28 rs6444305 in LPP gene is associated with follicular lymphoma. (PMID:25279986)
• alteration of LPP expression markedly changes the collectiveness and metastatic potential of cancer cells (PMID:26028032)
• this study shows the importance of PP2A complexes with the LIM domains of lipoma-preferred partner in cell adhesion and migration dynamics (PMID:26945059)
• meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in Europeans and Americans (PMID:28208589)
• Data indicate a function for lipoma preferred partner (LPP) in the formation of invadopodia and a requirement for LPP in mediating the metastatic ability of breast cancer cells. (PMID:28436416)
• This is the first report of epigenetic regulation of the intronic miR-28-5p expression by promoter DNA methylation of its host gene, LPP. (PMID:28775176)
• cancer-associated fibroblasts regulate endothelial LPP via a calcium-dependent signaling pathway involving microfibrillar-associated protein 5 (MFAP5), focal adhesion kinase (FAK), ERK, and LPP (PMID:29251630)
• Our results provides evidence for the impact of LPP polymorphisms on the susceptibility to lung cancer in Chinese population (PMID:30621612)
• The results of the stratified analysis showed that LPP SNPs rs3796283 and rs2378456 in the Chinese Han population were connected with susceptibility to Immunoglobulin A nephropathy (IgAN) in different subgroups. Our data may provide new evidence to research the etiology of IgAN. (PMID:31295688)
• LPP rs2378456 CC genotype increased the risk of astrocytoma. (PMID:31440994)
• Case Report: Identification of Potential Prognosis-Related TP53 Mutation and BCL6-LPP Fusion in Primary Pituitary Lymphoma by Next Generation Sequencing: Two Cases. (PMID:34381423)
• LPP polymorphisms are risk factors for allergic rhinitis in the Chinese Han population. (PMID:36084606)
• Replication of association at the LPP and UBASH3A loci in a UK autoimmune Addison’s disease cohort. (PMID:36651163)
• Association of LPP and ZMIZ1 Gene Polymorphism with Celiac Disease in Subjects from Punjab, Pakistan. (PMID:39062631)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpp	ENSDARG00000023578
mus_musculus	Lpp	ENSMUSG00000033306
rattus_norvegicus	Lpp	ENSRNOG00000031669

Paralogs (1): FBLIM1 (ENSG00000162458)

Protein

Protein identifiers

Lipoma-preferred partner — Q93052 (reviewed: Q93052)

Alternative names: LIM domain-containing preferred translocation partner in lipoma

All UniProt accessions (14): Q93052, A0A087WZF1, A0AA34QW10, B7Z8W0, C9J1K7, C9J2R5, C9J3U9, C9J4E3, C9J5C8, C9JE51, C9JIY7, C9JT42, C9JUT4, C9JXK9

UniProt curated annotations — full annotation on UniProt →

Function. May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus.

Subunit / interactions. Interacts with VASP, with PDZ domains of SCRIB and with ACTN1/alpha-actinin.

Subcellular location. Nucleus. Cytoplasm. Cell junction. Cell membrane.

Tissue specificity. Expressed in a wide variety of tissues but no or very low expression in brain and peripheral leukocytes.

Disease relevance. A chromosomal aberration involving LPP is associated with a subclass of benign mesenchymal tumors known as lipomas. Translocation t(3;12)(q27-q28;q13-q15) with HMGA2 is shown in lipomas. A chromosomal aberration involving LPP is associated with pulmonary chondroid hamartomas. Translocation t(3;12)(q27-q28;q14-q15) with HMGA2 is detected in pulmonary chondroid hamartomas. A chromosomal aberration involving LPP is associated with parosteal lipomas. Translocation t(3;12)(q28;q14) with HMGA2 is also shown in one parosteal lipoma. A chromosomal aberration involving LPP is associated with acute monoblastic leukemia. Translocation t(3;11)(q28;q23) with KMT2A/MLL1 is associated with acute monoblastic leukemia.

Similarity. Belongs to the zyxin/ajuba family.

RefSeq proteins (35): NP_001161143, NP_001161144, NP_001362384, NP_001362385, NP_001362386, NP_001362387, NP_001362388, NP_001362389, NP_001362390, NP_001362391, NP_001362392, NP_001362393, NP_001362394, NP_001374592, NP_001374593, NP_001374594, NP_001374595, NP_001374596, NP_001374597, NP_001374598, NP_001374599, NP_001374600, NP_001374601, NP_001374602, NP_001374603, NP_001374604, NP_001374605, NP_001374606, NP_001374607, NP_001374608, NP_001374609, NP_001374610, NP_001374611, NP_001374612, NP_005569 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain

Pfam: PF00412

UniProt features (29 total): compositionally biased region 7, modified residue 7, domain 3, sequence variant 3, region of interest 3, site 2, mutagenesis site 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93052-F1	60.99	0.26

Functional residue map

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

Catalytic / active sites (2): 371–372 (breakpoint for translocation to form hmga2-lpp); 470–471 (breakpoint for translocation to form hmga2-lpp and kmt2a/mll1-lpp)

Post-translational modifications (8): 108, 116, 151, 244, 301, 333, 375, 327

Mutagenesis-validated functional residues (2):

Position	Phenotype
610	abolishes binding to scrib.
612	abolishes binding to scrib.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 457 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, TAATAAT_MIR126, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, HNF1_Q6, HEIDENBLAD_AMPLICON_8Q24_DN, SRF_Q5_01, GOBP_CELL_CELL_ADHESION, GTGCCTT_MIR506, MAHAJAN_RESPONSE_TO_IL1A_DN, BROWNE_HCMV_INFECTION_48HR_DN

GO Biological Process (2): cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (8): stress fiber (GO:0001725), nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cytoplasm (GO:0005737), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell adhesion	1
cellular process	1
cation binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPP	LASP1	Q14847	930
LPP	F5H6H0	F5H6H0	813
LPP	ETV4	P43268	696
LPP	LHFPL6	Q9Y693	649
LPP	COX6C	P09669	649
LPP	CCNB1IP1	Q9NPC3	648
LPP	VASP	P50552	637
LPP	PALLD	Q8WX93	598
LPP	BLOC1S6	Q9UL45	591
LPP	PPP2R3A	Q06190	551
LPP	NEBL	O76041	546
LPP	RITA1	Q96K30	533
LPP	TLR2	O60603	525
LPP	SCRIB	Q14160	524
LPP	ZYX	Q15942	521

IntAct

60 interactions, top by confidence:

A	B	Type	Score
PPP2R3A	PPP2R1A	psi-mi:“MI:0914”(association)	0.920
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PDLIM7	BAG3	psi-mi:“MI:0914”(association)	0.800
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
TJP2	LASP1	psi-mi:“MI:0914”(association)	0.580
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
CBLC	GAK	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
WASF3	HOXB9	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
LASP1	ZYX	psi-mi:“MI:0914”(association)	0.420
LPP	LASP1	psi-mi:“MI:2364”(proximity)	0.420
MTNR1A	LPP	psi-mi:“MI:0915”(physical association)	0.370
LPP	SVIL	psi-mi:“MI:0915”(physical association)	0.370
PPP2R1A	INTS2	psi-mi:“MI:0914”(association)	0.350
Sestd1	CFL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (153): LPP (Affinity Capture-MS), LPP (Affinity Capture-MS), LPP (Co-fractionation), LPP (Co-fractionation), LPP (Co-fractionation), LPP (Proximity Label-MS), LPP (Affinity Capture-MS), LPP (Affinity Capture-MS), LPP (Affinity Capture-MS), LPP (Affinity Capture-MS), LPP (Proximity Label-MS), LPP (Affinity Capture-MS), LPP (Affinity Capture-MS), LPP (Affinity Capture-MS), LPP (Affinity Capture-MS)

ESM2 similar proteins: A0JMZ1, A1L209, A1L2F3, A1L3I5, A2AWT3, A4FUE7, A6QQM4, O82171, O94519, P97868, Q08AZ1, Q14CW9, Q1W1G1, Q22122, Q2HJG4, Q2YDJ0, Q32KN7, Q5EAW4, Q5PPV5, Q5REC0, Q5TFG8, Q5ZMS6, Q618K0, Q62920, Q64GL0, Q66HC1, Q6DGN6, Q6NRP6, Q6P1U3, Q6V5K9, Q7SXT7, Q7Z6E9, Q801E2, Q8BJH1, Q8CI51, Q8H100, Q8IMP6, Q8IYB5, Q8R550, Q91W18

Diamond homologs: A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q13796, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7, Q55BI0, Q5F464, Q5R7I1, Q5RCF7, Q5TD97, Q5U2Z2, Q5XI07

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ROCK2	“up-regulates quantity by expression”	LPP	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	LPP	“transcriptional regulation”
ROCK1	“up-regulates quantity by expression”	LPP	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Regulation of PLK1 Activity at G2/M Transition	6	16.2×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	5	17.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	113
Likely benign	14
Benign	39

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
545291	NC_000003.12:g.(?188343948)(188435451_?)del	Likely pathogenic
545292	NC_000003.12:g.(?188420063)(188540464_?)del	Likely pathogenic

SpliceAI

3721 predictions. Top by Δscore:

Variant	Effect	Δscore
3:188260739:A:T	donor_gain	1.0000
3:188343693:G:GT	donor_gain	1.0000
3:188406312:GG:G	donor_gain	1.0000
3:188406313:GG:G	donor_gain	1.0000
3:188484587:T:A	acceptor_gain	1.0000
3:188484590:A:AG	acceptor_gain	1.0000
3:188484590:AGGT:A	acceptor_gain	1.0000
3:188484591:G:GG	acceptor_gain	1.0000
3:188484591:GGT:G	acceptor_gain	1.0000
3:188484591:GGTG:G	acceptor_gain	1.0000
3:188524659:CAACA:C	acceptor_loss	1.0000
3:188524660:AACAG:A	acceptor_gain	1.0000
3:188524662:CAGGG:C	acceptor_loss	1.0000
3:188524663:A:AG	acceptor_gain	1.0000
3:188524663:AG:A	acceptor_gain	1.0000
3:188524663:AGG:A	acceptor_gain	1.0000
3:188524663:AGGG:A	acceptor_gain	1.0000
3:188524664:G:C	acceptor_loss	1.0000
3:188524664:G:GA	acceptor_gain	1.0000
3:188524664:GG:G	acceptor_gain	1.0000
3:188524664:GGG:G	acceptor_gain	1.0000
3:188524664:GGGG:G	acceptor_gain	1.0000
3:188524664:GGGGA:G	acceptor_gain	1.0000
3:188524783:CACAG:C	donor_loss	1.0000
3:188524784:ACAGG:A	donor_loss	1.0000
3:188524785:CAGG:C	donor_loss	1.0000
3:188524786:AGGT:A	donor_loss	1.0000
3:188524788:G:T	donor_loss	1.0000
3:188225507:G:T	donor_gain	0.9900
3:188225526:TGGT:T	donor_loss	0.9900

AlphaMissense

3950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:188524729:T:C	L124S	1.000
3:188524729:T:G	L124W	1.000
3:188524741:T:C	L128S	1.000
3:188708340:T:C	L396P	1.000
3:188760118:T:A	C416S	1.000
3:188760118:T:C	C416R	1.000
3:188760119:G:A	C416Y	1.000
3:188760119:G:C	C416S	1.000
3:188760120:T:G	C416W	1.000
3:188760127:T:C	C419R	1.000
3:188760160:T:C	C430R	1.000
3:188760162:C:G	C430W	1.000
3:188760167:C:A	A432D	1.000
3:188760181:T:C	F437L	1.000
3:188760183:C:A	F437L	1.000
3:188760183:C:G	F437L	1.000
3:188760193:T:C	C441R	1.000
3:188760195:T:G	C441W	1.000
3:188760196:T:C	F442L	1.000
3:188760197:T:C	F442S	1.000
3:188760198:T:A	F442L	1.000
3:188760198:T:G	F442L	1.000
3:188760202:T:C	C444R	1.000
3:188760203:G:A	C444Y	1.000
3:188760203:G:T	C444F	1.000
3:188760204:C:G	C444W	1.000
3:188760224:T:C	L451P	1.000
3:188760238:T:C	F456L	1.000
3:188760239:T:C	F456S	1.000
3:188760240:C:A	F456L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001947 (3:188719241 G>A), RS1000003709 (3:188277979 A>G), RS1000011864 (3:188741007 G>C), RS1000016848 (3:188391271 T>C), RS1000018903 (3:188569239 T>C), RS1000020549 (3:188843290 T>C), RS1000036149 (3:188481345 A>G), RS1000036347 (3:188576422 A>G), RS1000047809 (3:188694237 A>T), RS1000056887 (3:188755902 C>A), RS1000063033 (3:188660769 T>G), RS1000073595 (3:188700623 C>G), RS1000079864 (3:188320689 A>G), RS1000080594 (3:188400696 C>A), RS1000082877 (3:188303400 G>A,T)

Disease associations

OMIM: gene MIM:600700 | disease phenotypes: MIM:601626, MIM:181500

GenCC curated gene-disease

Mondo (2): acute myeloid leukemia (MONDO:0018874), schizophrenia (MONDO:0005090)

Orphanet (2): Acute myeloid leukemia (Orphanet:519), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

3 total (4 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0004808	Acute myeloid leukemia
HP:0100753	Schizophrenia

GWAS associations

117 associations (top):

Study	Trait	p-value
GCST000157_4	Celiac disease	5.000000e-09
GCST000612_3	Celiac disease	3.000000e-40
GCST000662_9	Vitiligo	1.000000e-11
GCST001201_20	Response to platinum-based chemotherapy (cisplatin)	4.000000e-06
GCST001316_11	IgE levels	2.000000e-06
GCST001523_19	Visceral adipose tissue adjusted for BMI	9.000000e-06
GCST001524_41	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-06
GCST001538_2	Immune reponse to smallpox (secreted IFN-alpha)	8.000000e-08
GCST001610_11	Renal function-related traits (BUN)	9.000000e-30
GCST001670_4	Vitiligo	9.000000e-08
GCST001762_529	Obesity-related traits	9.000000e-06
GCST001764_4	White matter integrity (bipolar disorder risk interaction)	6.000000e-06
GCST002066_1	B cell non-Hodgkin lymphoma	3.000000e-13
GCST002083_14	Self-reported allergy	1.000000e-09
GCST002084_4	Allergic sensitization	3.000000e-10
GCST002339_1	Type 2 diabetes (young onset) and obesity	7.000000e-06
GCST002352_29	Type 2 diabetes	6.000000e-09
GCST002643_4	Follicular lymphoma	1.000000e-10
GCST002726_54	Glucose homeostasis traits	2.000000e-07
GCST002726_68	Glucose homeostasis traits	3.000000e-06
GCST002806_5	Type 2 diabetes	2.000000e-06
GCST003468_22	Chronic lymphocytic leukemia	4.000000e-08
GCST003622_15	Systemic lupus erythematosus	4.000000e-15
GCST003622_6	Systemic lupus erythematosus	6.000000e-07
GCST003622_61	Systemic lupus erythematosus	8.000000e-10
GCST003655_12	Cutaneous squamous cell carcinoma	1.000000e-07
GCST003726_22	Basal cell carcinoma	1.000000e-14
GCST003817_4	Mortality in sepsis	2.000000e-07
GCST003987_19	Asthma	7.000000e-09
GCST003990_21	Allergy	3.000000e-08

EFO canonical traits (33, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005188	CCL11 measurement
EFO:0004641	white matter integrity
EFO:0005298	allergic sensitization measurement
EFO:0006833	glucose effectiveness measurement
EFO:0004471	insulin sensitivity measurement
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0004352	mortality
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004695	intraocular pressure measurement
EFO:0004847	age at onset
EFO:0009933	Thyroid preparation use measurement
EFO:0009941	Inhalant adrenergic use measurement
EFO:0006917	spontaneous preterm birth
EFO:0010176	keratinocyte carcinoma
EFO:0004530	triglyceride measurement
EFO:0008328	chronotype measurement
EFO:0007863	illness severity status
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs77693286	LPP		0.00	0
rs6790761	LPP		0.00	0
rs1975991	LPP		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation, increases mutagenesis, affects cotreatment (+1 more)	8
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	5
Aflatoxin B1	decreases methylation, increases methylation, affects expression, decreases expression	4
methylmercuric chloride	increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Cisplatin	affects cotreatment, decreases expression	2
Doxorubicin	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression, decreases methylation	2
Tretinoin	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
2-butenal	decreases expression	1
sodium bichromate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00000589	PHASE3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990	PHASE3	COMPLETED	Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606	PHASE3	TERMINATED	Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120	PHASE3	COMPLETED	Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878	PHASE3	TERMINATED	Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255	PHASE3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594	PHASE3	TERMINATED	Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966	PHASE3	COMPLETED	Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512	PHASE3	WITHDRAWN	To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832	PHASE3	COMPLETED	Trial of Decitabine in Patients With Acute Myeloid Leukemia