LPP (lipoma preferred partner)

2004-05-01 Marleen M Petit Affiliation

Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven (K.U.Leuven) & VIB, Herestraat 49, B-3000 Leuven, Belgium

Identity

HGNC

LPP

LOCATION

3q28

IMAGE

LEGEND

Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

LOCUSID

4026

ALIAS

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

At least 11 exons; predicted start codon in exon 3, stop codon in exon 11; the protein coding region is covered by the overlapping "CEPH Mark 1" YAC clones 135H6 and 192B10 (start codon in 135H6, stop codon in 192B10) and is dispersed over at least 400 kb genomic DNA; the LIM domains are encoded by separate exons: LIM 1 is encoded by exon 8, LIM 2 by exon 9, and LIM 3 by exon 10 and part of exon 11.

Transcription

mRNA: ubiquitously: > 10 kb; testis: additional transcripts of 1.8 kb and 1.25 kb

Pseudogene

no pseudogenes

Proteins

Description

612 amino acids; proline-rich region (amino-terminal 2/3 of the protein) followed by three LIM domains (carboxy-terminal 1/3 of the protein). Proline-rich region contains an alfa-actinin binding site, two VASP-binding motifs, and a nuclear export signal.

Expression

Smooth muscle marker; readily detected on Western blot with an LPP-antibody in all fibroblastic and epithelial cell lines tested to date.

Localisation

LPP is present in the cytoplasm of cells as well as at sites of cell adhesion such as focal adhesions (attachments sites to the extracellular matrix) and cell-cell contacts; LPP also shuttles to the nucleus and its nuclear-cytoplasmic localisation is regulated in part by a nuclear export signal (NES) which is sensitive to the drug leptomycin B.

Function

Because of their structural features (many protein-protein interaction domains) and their characteristic to shuttle between the nucleus and the cytoplasm, LPP and its family members (see below) have been proposed to be scaffolding proteins involved in signal transduction from sites of cell adhesion to the nucleus; LPP has been shown to harbour transcriptional activation capacity in luciferase reporter assays, suggesting that LPP may be directly involved in the regulation of gene expression; LPP was found to be highly expressed in smooth muscle, and a role for LPP in regulating cell motility was proposed; the precise function of LPP remains to be elucidated.

Homology

LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. The family hallmark of these proteins are three clustered LIM domains at the carboxy-terminus, which are protein interaction domains. All family members are present at sites of cell adhesion and have the ability to shuttle to the nucleus, and all family members have one or more nuclear export signals.

Mutations

Somatic

HMGA2/LPP fusion proteins and MLL/LPP fusion proteins (Fig2).

Implicated in

Entity name

solitary lipomas

Disease

Benign tumors of adipose tissue.

Prognosis

Can be surgically removed with no recurrence in most cases.

Cytogenetics

More than 60% of solitary lipomas have an aberrant karyotype; 2/3 of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/4 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene.

Hybrid gene

HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 8-11 or 9-11 of LPP; under the regulation of the HMGA2 promoter.

Fusion protein

HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by two LIM domains (LIM 2 and LIM 3) or a portion of the proline-rich region and all three LIM domains of LPP.

Entity name

Pulmonary chondroid hamartomas

Disease

Benign mesenchymal tumors of the lung.

Prognosis

good

Cytogenetics

More than 70% of pulmonary chondroid hamartomas have an aberrant karyotype; 70% of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/8 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene.

Hybrid gene

HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.

Fusion protein

HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.

Entity name

Parosteal lipoma

Disease

Rare deep-seated benign tumor of adipose tissue comprising less than 0.5% of all lipomas; parosteal lipomas exhibit a contiguous relationship with the periostium; because of their intimate relationship to the bone, they are considered as lipomas of bone.

Prognosis

Most often asymptomatic; in some cases: loss of motor and/or sensory function as a result of the compression or stretching of a nerve.

Cytogenetics

One case reported with rearrangement of LPP t(3;12)(q28;q14).

Hybrid gene

HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.

Fusion protein

HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.

Entity name

Soft tissue chondroma

Disease

Benign tumor of cartilage; rare entity.

Cytogenetics

Only 31 cases with abnormal karyotypes have been reported (11-2003); 12q15 nonrandomly involved; one case reported with rearrangement of LPP t(3;12)(q27;q15).

Hybrid gene

HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.

Fusion protein

HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.

Entity name

AML-M5

Disease

Secondary leukemia following treatment with DNA topoisomerase II inhibitors.

Cytogenetics

MLL gene on 11q23 frequently involved; one case reported with rearrangement of LPP t(3;11)(q28;q23).

Hybrid gene

MLL/LPP hybrid gene containing the first 8 exons of MLL and exons 9-11 of LPP; under the regulation of the MLL promoter.

Fusion protein

MLL/LPP fusion transcripts encode the three DNA-binding domains and the methyltransferase-like domain of MLL followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.

Breakpoints

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11433529	2001	Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).	Dahéron L et al
14614053	2003	Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas.	Dahlén A et al
12760907	2003	LPP, a LIM protein highly expressed in smooth muscle.	Gorenne I et al
12063392	2001	A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas.	Lemke I et al
12615977	2003	The lipoma preferred partner LPP interacts with alpha-actinin.	Li B et al
12869577	2003	Prediction of cell type-specific gene modules: identification and initial characterization of a core set of smooth muscle-specific genes.	Nelander S et al
10637295	2000	LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity.	Petit MM et al
12441356	2003	The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.	Petit MM et al
8812423	1996	LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family.	Petit MM et al
9772904	1998	Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma.	Petit MM et al
9598796	1998	The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an adipocytic phenotype.	Rogalla P et al

Other Information

Locus ID:

NCBI: 4026
MIM: 600700
HGNC: 6679
Ensembl: ENSG00000145012

Variants:

dbSNP: 4026
ClinVar: 4026
TCGA: ENSG00000145012
COSMIC: LPP

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000145012	ENST00000414139	C9J1K7
ENSG00000145012	ENST00000415906	C9JXK9
ENSG00000145012	ENST00000416784	C9J4E3
ENSG00000145012	ENST00000420410	C9J5C8
ENSG00000145012	ENST00000426274	C9J3U9
ENSG00000145012	ENST00000430340	C9J2R5
ENSG00000145012	ENST00000443217	C9JE51
ENSG00000145012	ENST00000448637	C9JUT4
ENSG00000145012	ENST00000454789	C9JT42
ENSG00000145012	ENST00000457242	C9JIY7
ENSG00000145012	ENST00000617246	Q93052
ENSG00000145012	ENST00000618621	A0A087WZF1
ENSG00000145012	ENST00000640853	Q93052

Expression (GTEx)

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
36651163	2023	Replication of association at the LPP and UBASH3A loci in a UK autoimmune Addison's disease cohort.	2
36651163	2023	Replication of association at the LPP and UBASH3A loci in a UK autoimmune Addison's disease cohort.	2
36084606	2022	LPP polymorphisms are risk factors for allergic rhinitis in the Chinese Han population.	2
36084606	2022	LPP polymorphisms are risk factors for allergic rhinitis in the Chinese Han population.	2
34381423	2021	Case Report: Identification of Potential Prognosis-Related TP53 Mutation and BCL6-LPP Fusion in Primary Pituitary Lymphoma by Next Generation Sequencing: Two Cases.	3
34381423	2021	Case Report: Identification of Potential Prognosis-Related TP53 Mutation and BCL6-LPP Fusion in Primary Pituitary Lymphoma by Next Generation Sequencing: Two Cases.	3
30621612	2019	Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.	6
31295688	2019	3'UTR SNPs in the LPP gene associated with Immunoglobulin A nephropathy risk in the Chinese Han population.	1
31440994	2019	LPP and RYR2 Gene Polymorphisms Correlate with the Risk and the Prognosis of Astrocytoma.	2
30621612	2019	Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.	6
31295688	2019	3'UTR SNPs in the LPP gene associated with Immunoglobulin A nephropathy risk in the Chinese Han population.	1
31440994	2019	LPP and RYR2 Gene Polymorphisms Correlate with the Risk and the Prognosis of Astrocytoma.	2
28775176	2018	Epigenetic silencing of LPP/miR-28 in multiple myeloma.	9
29251630	2018	Cancer-associated fibroblasts regulate endothelial adhesion protein LPP to promote ovarian cancer chemoresistance.	68
28775176	2018	Epigenetic silencing of LPP/miR-28 in multiple myeloma.	9

Citation

Marleen M Petit

LPP (lipoma preferred partner)

Atlas Genet Cytogenet Oncol Haematol. 2004-05-01

Online version: http://atlasgeneticsoncology.org/gene/72/lpp-(lipoma-preferred-partner)