LASP1

Chr 17

LIM and SH3 protein 1

Also known as: Lasp-1, MLN50

NCBI Gene: 3927UniProt: Q14847

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. [provided by RefSeq, Oct 2012]

42
ClinVar variants
7
Pathogenic / LP
0.98
pLI score· HI
2.2
Missense Z
0.28
LOEUF· LoF intolerant
0
Active trials
Clinical Summary— LASP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 31 VUS of 42 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.983
Z-score 3.57
OE 0.06 (0.02–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.21Z-score
OE missense 0.54 (0.46–0.64)
101 obs / 185.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.46–0.64)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 1 / 16.8Missense obs/exp: 101 / 185.6Syn Z: 0.22

ClinVar Variant Classifications

42 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
VUS31
Likely Benign2
Benign2
7
Pathogenic
31
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
28
3
0
31
Likely Benign
0
1
0
1
2
Benign
0
0
0
2
2
Total02910342

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LASP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
LASP1 in Tumor and Tumor Microenvironment.
Hu Z et al.·Curr Mol Med
2017Review
CXCR4-LASP1-G9a-SNAIL axis drives NEPC transdifferentiation via induction of EMT and downregulation of REST.
Liu L et al.·Cell Genom
2025
Paving the path for invasion: The polyedric role of LASP1 in cancer.
Ruggieri V et al.·Tumour Biol
2017Review
E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.
Patterson MR et al.·Oncogene
2024
Molecular Determinants of Medulloblastoma Metastasis and Leptomeningeal Dissemination.
Li M et al.·Mol Cancer Res
2021Review
CERS6-AS1 Facilitates Oncogenesis and Restrains Ferroptosis in Papillary Thyroid Carcinoma by Serving as a ceRNA through miR-497-5p/LASP1 Axis.
Huang T et al.·Ann Clin Lab Sci
2022
Identification of miR-1-3p, miR-143-3p and miR-145-5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation.
Guo H et al.·Mol Cell Probes
2023
Astragaloside IV regulates circ_0001615 and miR-873-5p/LASP1 axis to suppress colorectal cancer cell progression.
Kong P et al.·Chem Biol Drug Des
2024
Loss of the 14-3-3σ is essential for LASP1-mediated colorectal cancer progression via activating PI3K/AKT signaling pathway.
Shao Z et al.·Sci Rep
2016
LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling.
Niu Y et al.·Sci Rep
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
LASP1 in Cellular Signaling and Gene Expression: More than Just a Cytoskeletal Regulator
Butt E et al.·Cells
2022
LIM and SH3 protein 1 (LASP1) differentiates malignant chordomas from less malignant chondrosarcomas
Vanderheijden C et al.·J Neurooncol
2022
LASP1, CERS6, and Actin Form a Ternary Complex That Promotes Cancer Cell Migration
Niimi A et al.·Cancers (Basel)
2023
Sevoflurane Suppresses Colon Cancer Cell Malignancy by Regulating circ-PI4KA
Sun S et al.·Onco Targets Ther
2021
Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis
You H et al.·Cell Commun Signal
2021
Circular RNA circSLC7A11 contributes to progression and stemness of laryngeal squamous cell carcinoma via sponging miR-877-5p from LASP1
Yu W et al.·Heliyon
2023
miR-218-5p in endometrial microenvironment prevents the migration of ectopic endometrial stromal cells by inhibiting LASP1
Zhang Z et al.·Reprod Biol Endocrinol
2022
Lasp1 Expression Is Implicated in Embryonic Development of Zebrafish
Grossi I et al.·Genes (Basel)
2022Functional
ECHS1, an interacting protein of LASP1, induces sphingolipid-metabolism imbalance to promote colorectal cancer progression by regulating ceramide glycosylation
Li R et al.·Cell Death Dis
2021
HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance
Song D et al.·J Exp Clin Cancer Res
2021
Top 10 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients