LASP1

Summary

LASP1 (LIM and SH3 protein 1, HGNC:6513) is a protein-coding gene on chromosome 17q12, encoding LIM and SH3 domain protein 1 (Q14847). Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities.

This gene encodes a member of a subfamily of LIM proteins, characterized by a LIM motif and a domain of Src homology region 3, and also a member of the nebulin family of actin-binding proteins. The encoded protein is a cAMP and cGMP dependent signaling protein and binds to the actin cytoskeleton at extensions of the cell membrane. The encoded protein has been linked to metastatic breast cancer, hematopoetic tumors such as B-cell lymphomas, and colorectal cancer.

Source: NCBI Gene 3927 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• MANE Select transcript: NM_006148

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6513
Approved symbol	LASP1
Name	LIM and SH3 protein 1
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	MLN50, Lasp-1
Ensembl gene	ENSG00000002834
Ensembl biotype	protein_coding
OMIM	602920
Entrez	3927

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000318008, ENST00000419929, ENST00000433206, ENST00000443937, ENST00000579123, ENST00000581485, ENST00000584106, ENST00000585841, ENST00000883574, ENST00000883575, ENST00000883576, ENST00000918828, ENST00000946796

RefSeq mRNA: 2 — MANE Select: NM_006148 NM_001271608, NM_006148

CCDS: CCDS11331, CCDS62164

Canonical transcript exons

ENST00000318008 — 7 exons

Exon	Start	End
ENSE00001277407	38918605	38921770
ENSE00002711323	38870058	38870258
ENSE00003462733	38915043	38915146
ENSE00003474352	38914325	38914475
ENSE00003517497	38890420	38890504
ENSE00003568004	38898412	38898519
ENSE00003604240	38878086	38878180

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 230.1370 / max 1627.3256, expressed in 1827 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160529	225.1232	1827
160528	1.0931	730
160538	0.7362	429
160534	0.6570	381
160542	0.6164	369
160539	0.4389	192
160540	0.3639	182
160543	0.2982	126
160537	0.2835	139
160527	0.2602	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	98.75	gold quality
jejunal mucosa	UBERON:0000399	98.72	gold quality
ileal mucosa	UBERON:0000331	98.64	gold quality
mammary duct	UBERON:0001765	98.58	gold quality
duodenum	UBERON:0002114	98.29	gold quality
stromal cell of endometrium	CL:0002255	98.21	gold quality
epithelium of mammary gland	UBERON:0003244	98.16	gold quality
superficial temporal artery	UBERON:0001614	98.10	gold quality
trabecular bone tissue	UBERON:0002483	98.07	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.04	gold quality
thymus	UBERON:0002370	97.94	gold quality
pylorus	UBERON:0001166	97.83	gold quality
blood	UBERON:0000178	97.82	gold quality
cardia of stomach	UBERON:0001162	97.81	gold quality
nasal cavity epithelium	UBERON:0005384	97.81	gold quality
tibia	UBERON:0000979	97.79	gold quality
granulocyte	CL:0000094	97.76	gold quality
colonic mucosa	UBERON:0000317	97.73	gold quality
olfactory bulb	UBERON:0002264	97.65	gold quality
amniotic fluid	UBERON:0000173	97.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.40	gold quality
mucosa of transverse colon	UBERON:0004991	97.35	gold quality
germinal epithelium of ovary	UBERON:0001304	97.30	gold quality
caecum	UBERON:0001153	97.28	gold quality
epithelium of nasopharynx	UBERON:0001951	97.18	gold quality
mucosa of urinary bladder	UBERON:0001259	97.12	gold quality
vermiform appendix	UBERON:0001154	97.09	gold quality
gingival epithelium	UBERON:0001949	97.07	gold quality
rectum	UBERON:0001052	97.06	gold quality
ventricular zone	UBERON:0003053	97.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	24.58
E-ANND-3	yes	7.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

168 targeting LASP1, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-17-5P	99.89	73.83	2665

Literature-anchored findings (GeneRIF, showing 40)

• In rabbits, lasp-1 localizes to sites of dynamic actin assembly, identifies sites that are phosphorylated by protein kinase A in vivo, and shows that the phosphorylation of these sites decreases F-actin-binding to lasp-1. (PMID:12432067)
• phosphorylation of LASP by cGK and cAK may be involved in cytoskeletal organization and cell motility (PMID:12571245)
• LIM-nebulette, Lasp-1, and zyxin may play an important role in the organization of focal adhesions (PMID:15004028)
• Data suggest that there are no functional differences between human and mouse LASP-1. (PMID:15465019)
• LASP-1 has an essential role in tumor cell growth and migration, possibly by influencing the localization of zyxin. (PMID:16430883)
• LASP-1 has an essential role in growth and migration of ovarian carcinoma cells, possibly by influencing the localization of zyxin. (PMID:17211471)
• LASP-1 may have roles in progression of human breast carcinoma (PMID:17956604)
• p53 may play a role in influencing tumor metastasis through Lasp1 in hepatocellular caarcinoma. (PMID:19155088)
• The ectopic expression of LASP-1 and uPA supported the proteomic results and showed that uPA up-regulation increased LASP-1 expression and that both were implicated in SKHep1C3 motility. (PMID:19177205)
• LASP-1 translocation to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase (PMID:19718473)
• LASP-1 interaction with CXCR2 is critical for CXCR2-mediated chemotaxis (PMID:20419088)
• Nuclear LASP-1-positivity may serve as a negative prognostic indicator for long-term survival of breast cancer patients. (PMID:20461080)
• Overexpression of LASP-1 was found in metastatic colorectal cancer (CRC) tissues (p=0.002), and its expression level was closely correlated with overall survival of patients with CRC (p=0.002). (PMID:20660701)
• Data indicate that LASP1 may have an oncogenic function and that it might be regulated by miR-1, miR-133a, and miR-218, which may function as tumor suppressive miRNAs in bladder cancer (BC). (PMID:20843712)
• LASP1 knockdown by small interfering RNA-mediated silencing indicates its funcion role in progression and metastasis of medulloblastoma. (PMID:20924110)
• LASP-1 gene expression enhances proliferation of colorectal cancer cells and may serve as a useful marker for colorectal cancer progression. (PMID:21215099)
• Data indicate decreased cell migratory potential accompanied by enhanced cell adhesion, but no significant inhibition of cell proliferation as measured by in T24 cells upon LIM and SH3 (LASP)-1 protein (LASP-1) knockdown. (PMID:22481019)
• Data indicate that Lasp-1 is a novel component of podosomes and is involved in the regulation of podosomal function. (PMID:22514729)
• Phosphorylation of LASP-1 by PKA at serine 146 induces translocation of the LASP-1/ZO-2 complex from the cytoplasm to the nucleus. (PMID:22665060)
• Up-regulated of BIRC5 and LASP1 was able to abrogate the effects induced by transfection with the miR-203 precursor in triple negative breast cancer. (PMID:22713668)
• These results demonstrated that hepatitis B virus X protein could upregulate LASP-1 through PI3-K pathway to promote the proliferation and migration of hepatoma cells. (PMID:22897902)
• miR-203 inhibits the migration and invasion of esophageal squamous cell carcinoma by regulating LASP1. (PMID:22940702)
• A single-nucleotide polymorphism in the LASP1 gene promoter region is associated with schizophrenia susceptibility. (PMID:23040864)
• High cytosolic LASP-1 expression is associated with hepatocellular carcinoma. (PMID:23084841)
• LASP1 may play an important role in the pathogenesis of esophageal squamous cell carcinoma. (PMID:23254782)
• Data show that miR-133a can target the 3’ untranslated region (3’UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1. (PMID:23968734)
• LASP-1 is linked closely to tumourigenicity in oral cancer. (PMID:24386158)
• Results show significant upregulation of LASP1 and SCAD protein levels in acute psychotic bipolar disorder samples. (PMID:24554194)
• LASP1 was a direct target of miR-218 in prostate cells. (PMID:24815849)
• Study revealed that LASP1 phosphorylation results in an association with CRKL - another specific BCR-ABL substrate and bona fide biomarker for BCR-ABL activity. (PMID:24913448)
• LASP-1 overexpression was associated with aggressive phenotype in clear cell renal cell cancer. (PMID:24955835)
• LASP-1, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the growth and metastasis of gastric cancer. (PMID:24990592)
• LIM and SH3 protein 1 induces TGFbeta-mediated epithelial-mesenchymal transition in human colorectal cancer by regulating S100A4 expression. (PMID:25252758)
• Results defined LASP1 as a direct target gene for HIF1alpha upregulation that is critical for metastatic progression of PDAC. (PMID:25385028)
• LASP1 plays key roles in cell structure, physiological processes, and cell signaling; overexpression contributes to cancer aggressiveness [review] (PMID:25622104)
• Our results suggest that LASP-1 mRNA overexpression may be mainly implicated in female hepatocellular carcinoma (HCC) and cirrhotic HCCs; and that LASP1 may play its role with vimentin in HCC cells. (PMID:25760690)
• LASP-1 associated with UHRF1, G9a, Snail1 and di- and tri-methylated histoneH3 in a CXCL12-dependent manner based on immunoprecipitation and proximity ligation assays (PMID:25982273)
• Results identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release. (PMID:26061439)
• Detecting an affection of migratory processes after LASP-1 silencing, we propose that LASP-1 could impact on metastasis of CC [choriocarcinoma]cells. (PMID:26232936)
• It is a target gene of miR-1. (PMID:26414725)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nebl	ENSDARG00000021200
		ENSDARG00000113614
mus_musculus	Lasp1	ENSMUSG00000038366
rattus_norvegicus	Lasp1	ENSRNOG00000004132
drosophila_melanogaster	Lasp	FBGN0063485
caenorhabditis_elegans		WBGENE00018367

Paralogs (4): NEBL (ENSG00000078114), KY (ENSG00000174611), NEB (ENSG00000183091), NRAP (ENSG00000197893)

Protein

Protein identifiers

LIM and SH3 domain protein 1 — Q14847 (reviewed: Q14847)

Alternative names: Metastatic lymph node gene 50 protein

All UniProt accessions (5): Q14847, C9J9W2, F6S2S5, J3KSN1, K7ESD6

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types.

Subunit / interactions. Interacts with F-actin. Interacts with ANKRD54. Interacts with KBTBD10.

Subcellular location. Cytoplasm. Cell cortex. Cytoskeleton.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14847-1	1	yes
Q14847-2	2
Q14847-3	3

RefSeq proteins (2): NP_001258537, NP_006139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000900	Nebulin_repeat	Repeat
IPR001452	SH3_domain	Domain
IPR001781	Znf_LIM	Domain
IPR035630	Lasp1_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051759	LIM-SH3_domain_protein	Family

Pfam: PF00412, PF00880, PF14604

UniProt features (30 total): modified residue 10, strand 5, sequence conflict 3, domain 2, splice variant 2, repeat 2, compositionally biased region 2, chain 1, turn 1, helix 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3I35	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14847-F1	71.09	0.35

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 (10): 68, 75, 99, 104, 112, 118, 134, 146, 1, 42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 318 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GNF2_MSN, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, LUCAS_HNF4A_TARGETS_UP, FOXO1_01, GGGTGGRR_PAX4_03

GO Biological Process (2): monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (6): monoatomic ion transmembrane transporter activity (GO:0015075), cadherin binding (GO:0045296), metal ion binding (GO:0046872), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), focal adhesion (GO:0005925), cortical actin cytoskeleton (GO:0030864), postsynapse (GO:0098794), cytoskeleton (GO:0005856), cell cortex (GO:0005938)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
transport	1
monoatomic ion transport	1
transmembrane transport	1
transmembrane transporter activity	1
monoatomic ion transmembrane transport	1
cell adhesion molecule binding	1
cation binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
intracellular anatomical structure	1
cell-substrate junction	1
actin cytoskeleton	1
cortical cytoskeleton	1
synapse	1
intracellular membraneless organelle	1
cytoplasm	1
cell periphery	1

Protein interactions and networks

STRING

1416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LASP1	LPP	Q93052	930
LASP1	PALLD	Q8WX93	871
LASP1	ZYX	Q15942	823
LASP1	VASP	P50552	810
LASP1	MLLT6	P55198	798
LASP1	KLHL41	O60662	784
LASP1	CXCR1	P25024	767
LASP1	TRAF4	Q9BUZ4	737
LASP1	FNBP1	Q96RU3	653
LASP1	GMPS	P49915	557
LASP1	KNL1	Q8NG31	548
LASP1	ANKRD54	Q6NXT1	544
LASP1	SARNP	P82979	541
LASP1	UHRF1	Q96T88	533
LASP1	ZWILCH	Q9H900	517

IntAct

178 interactions, top by confidence:

A	B	Type	Score
TRIP13	LASP1	psi-mi:“MI:0915”(physical association)	0.820
LASP1	TRIP13	psi-mi:“MI:0915”(physical association)	0.820
LASP1	ZBTB9	psi-mi:“MI:0915”(physical association)	0.670
LASP1	STAT3	psi-mi:“MI:0915”(physical association)	0.620
STAT3	LASP1	psi-mi:“MI:0915”(physical association)	0.620
LASP1	MDFI	psi-mi:“MI:0915”(physical association)	0.620
MDFI	LASP1	psi-mi:“MI:0915”(physical association)	0.620
TJP2	LASP1	psi-mi:“MI:0915”(physical association)	0.580
LASP1	TJP2	psi-mi:“MI:2364”(proximity)	0.580
LASP1	TJP2	psi-mi:“MI:0914”(association)	0.580
TJP2	LASP1	psi-mi:“MI:0914”(association)	0.580
LASP1	ARHGEF15	psi-mi:“MI:0915”(physical association)	0.560
LASP1	SPRY2	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	LASP1	psi-mi:“MI:0915”(physical association)	0.560
LASP1	TCF4	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	LASP1	psi-mi:“MI:0915”(physical association)	0.560
FXR2	LASP1	psi-mi:“MI:0915”(physical association)	0.560
LASP1	REL	psi-mi:“MI:0915”(physical association)	0.560
LASP1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
ZC2HC1A	LASP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (323): LASP1 (Two-hybrid), PSMA3 (Two-hybrid), REL (Two-hybrid), TRIM27 (Two-hybrid), TCF4 (Two-hybrid), TRIP13 (Two-hybrid), FXR2 (Two-hybrid), SPRY2 (Two-hybrid), ARHGEF15 (Two-hybrid), ZC2HC1A (Two-hybrid), THAP1 (Two-hybrid), SEPT3 (Two-hybrid), LZTS2 (Two-hybrid), RHOXF2 (Two-hybrid), KRTAP4-2 (Two-hybrid)

ESM2 similar proteins: A6ZKU1, A7TKW4, B0W3R7, B7WN72, E7FDW2, F1M3L7, G5EBZ8, G5ECY0, G5EDM4, G5EGQ3, H2L099, O13736, O42478, P03949, P15330, P32790, P34400, P34416, P51140, P62484, Q04727, Q08509, Q10149, Q12929, Q14847, Q19469, Q22227, Q22638, Q5R4H4, Q5R5W0, Q61792, Q62441, Q6CL17, Q6NQK0, Q7PNM6, Q8AXB4, Q8CBW3, Q8IZP0, Q95RG8, Q99MZ8

Diamond homologs: A3LXQ8, A6H7G2, A6ZR73, A7MBI0, B3LRN4, B5VHP4, B8R1V5, C4Y1G1, C7GKW5, E7KBW4, E7KMS3, E7LTJ6, E7Q311, E7QE10, G5EC32, O13154, O35179, O35180, O42287, O60861, O74749, O75886, O76041, O77506, O88811, P08487, P10569, P10686, P14317, P18302, P19174, P20929, P34121, P34416, P40073, P49710, P70297, Q01406, Q07266, Q09822

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
ABL1	up-regulates	LASP1	phosphorylation
PRKACA	“down-regulates activity”	LASP1	phosphorylation
PRKG2	unknown	LASP1	phosphorylation
BCR-ABL	unknown	LASP1	phosphorylation
SRC	“up-regulates activity”	LASP1	phosphorylation
PRKCB	“down-regulates activity”	LASP1	phosphorylation
PRKG1	“down-regulates activity”	LASP1	phosphorylation
PRKACA	“up-regulates activity”	LASP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Signaling by Interleukins	8	5.6×	6e-03
Infectious disease	13	3.5×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of telomere maintenance via telomerase	5	30.8×	6e-04
positive regulation of telomere maintenance	5	21.5×	8e-04
positive regulation of gene expression	14	4.6×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1423 predictions. Top by Δscore:

Variant	Effect	Δscore
17:38870257:AGGT:A	donor_loss	1.0000
17:38870258:GG:G	donor_loss	1.0000
17:38870259:G:T	donor_loss	1.0000
17:38878082:CCAGT:C	acceptor_loss	1.0000
17:38878084:A:AG	acceptor_gain	1.0000
17:38878084:A:C	acceptor_loss	1.0000
17:38878085:G:GC	acceptor_gain	1.0000
17:38878085:GTT:G	acceptor_gain	1.0000
17:38878085:GTTCT:G	acceptor_gain	1.0000
17:38878177:ACGC:A	donor_gain	1.0000
17:38878177:ACGCG:A	donor_loss	1.0000
17:38878178:CGC:C	donor_gain	1.0000
17:38878179:GC:G	donor_gain	1.0000
17:38878179:GCG:G	donor_gain	1.0000
17:38878180:CGTG:C	donor_loss	1.0000
17:38878181:G:C	donor_loss	1.0000
17:38878181:G:GG	donor_gain	1.0000
17:38878182:T:G	donor_loss	1.0000
17:38878183:G:GC	donor_loss	1.0000
17:38890418:A:AG	acceptor_gain	1.0000
17:38890419:G:GT	acceptor_gain	1.0000
17:38890419:GA:G	acceptor_gain	1.0000
17:38890419:GAC:G	acceptor_gain	1.0000
17:38890419:GACA:G	acceptor_gain	1.0000
17:38890419:GACAC:G	acceptor_gain	1.0000
17:38890486:GA:G	donor_gain	1.0000
17:38890488:G:GG	donor_gain	1.0000
17:38898407:TGCA:T	acceptor_loss	1.0000
17:38898408:GCA:G	acceptor_loss	1.0000
17:38898409:CA:C	acceptor_loss	1.0000

AlphaMissense

1750 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:38878110:T:C	C32R	1.000
17:38878119:T:C	C35R	1.000
17:38918660:T:C	F223S	1.000
17:38918678:T:A	I229N	1.000
17:38918678:T:G	I229S	1.000
17:38918707:T:A	W239R	1.000
17:38918707:T:C	W239R	1.000
17:38918709:G:C	W239C	1.000
17:38918709:G:T	W239C	1.000
17:38918716:G:A	G242R	1.000
17:38918716:G:C	G242R	1.000
17:38918716:G:T	G242W	1.000
17:38918717:G:A	G242E	1.000
17:38918743:G:T	G251W	1.000
17:38918744:G:A	G251E	1.000
17:38918750:T:C	L253P	1.000
17:38870202:T:A	C5S	0.999
17:38870202:T:C	C5R	0.999
17:38870203:G:A	C5Y	0.999
17:38870203:G:C	C5S	0.999
17:38870204:C:G	C5W	0.999
17:38870211:T:A	C8S	0.999
17:38870211:T:C	C8R	0.999
17:38870212:G:A	C8Y	0.999
17:38870212:G:C	C8S	0.999
17:38870247:T:C	C20R	0.999
17:38870249:T:G	C20W	0.999
17:38878089:T:A	W25R	0.999
17:38878089:T:C	W25R	0.999
17:38878091:G:C	W25C	0.999

dbSNP variants (sampled 300 via entrez): RS1000017435 (17:38873935 C>A), RS1000063619 (17:38919844 T>C), RS1000069829 (17:38873756 C>T), RS1000093742 (17:38892205 G>A,T), RS1000126412 (17:38892483 G>T), RS1000138374 (17:38879751 C>CT), RS1000144274 (17:38904519 G>A), RS1000177351 (17:38904782 A>G), RS1000212779 (17:38896165 C>T), RS1000290502 (17:38897954 T>G), RS1000317997 (17:38895926 G>A), RS1000355604 (17:38870436 C>G), RS1000364882 (17:38904280 G>A), RS1000374446 (17:38887177 C>G,T), RS1000391607 (17:38870729 G>T)

Disease associations

OMIM: gene MIM:602920 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003075_19	Cognitive decline rate in late mild cognitive impairment	4.000000e-09
GCST008514_25	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0010103	response to peginterferon alfa-2a

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067303 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.33	Kd	4.673	nM	CHEMBL3752910
8.33	ED50	4.673	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148640: Binding affinity to human LASP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0047	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	4
Tretinoin	increases expression	3
bisphenol F	affects cotreatment, decreases expression, increases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression	2
Cadmium	increases expression	2
Doxorubicin	affects expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
afimoxifene	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
hydroquinone	affects expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
beta-methylcholine	affects expression	1
tamibarotene	increases expression	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
mono-benzyl phthalate	increases abundance, increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651682	Binding	Binding affinity to human LASP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1577	NCI-H661	Cancer cell line	Male
CVCL_1661	ZR-75-30	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome