NEDD9

Chr 6

neural precursor cell expressed, developmentally down-regulated 9

Also known as: CAS-L, CAS2, CASL, CASS2, HEF1

NCBI Gene: 4739ENSG00000111859UniProt: Q14511

The protein encoded by this gene is a member of the CRK-associated substrates family. Members of this family are adhesion docking molecules that mediate protein-protein interactions for signal transduction pathways. This protein is a focal adhesion protein that acts as a scaffold to regulate signaling complexes important in cell attachment, migration and invasion as well as apoptosis and the cell cycle. This protein has also been reported to have a role in cancer metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

146
ClinVar variants
26
Pathogenic / LP
0.13
pLI score
0
Active trials
Clinical Summary— NEDD9
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 111 VUS of 146 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.126
Z-score 4.18
OE 0.25 (0.15–0.43)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.86Z-score
OE missense 0.89 (0.82–0.96)
426 obs / 479.1 exp
Tolerant

Mild missense constraint

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.0.25 (0.15–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.96)
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.0.89
0≤1.21.6
LoF obs/exp: 9 / 36.1Missense obs/exp: 426 / 479.1Syn Z: 1.23

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic3
VUS111
Likely Benign8
Benign1
23
Pathogenic
3
Likely Pathogenic
111
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
3
0
3
VUS
0
111
0
0
111
Likely Benign
0
6
0
2
8
Benign
0
0
0
1
1
Total0117263146

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

View in ClinVar →

Protein Context — Lollipop Plot

NEDD9 · 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
Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and other diseases.
Shagisultanova E et al.·Gene
2015Review
NEDD9 is transcriptionally regulated by HDAC4 and promotes breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling pathway.
Liu W et al.·Neoplasia
2024
Macrophages downregulate NEDD9 to counteract S. Typhimurium- mediated FAK-AKT activation and lysosome inhibition.
Fischer J et al.·Cell Death Dis
2025
Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma.
Lerotić I et al.·Bosn J Basic Med Sci
2021
Expression of NEDD9 in hepatocellular carcinoma and its clinical significance.
Lu P et al.·Oncol Rep
2015
Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle.
Singh M et al.·Cell Biochem Biophys
2007Review
Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression.
Hu Z et al.·Signal Transduct Target Ther
2023
Nervous system in hepatocellular carcinoma: Correlation, mechanisms, therapeutic implications, and future perspectives.
Li W et al.·Biochim Biophys Acta Rev Cancer
2025Review
EIF4A3 Promotes Muscle Atrophy and Aging by Inhibiting the FAK Pathway Through NEDD9 mRNA Destabilization.
Li Q et al.·J Cachexia Sarcopenia Muscle
2025
NEDD9 overexpression correlates with poor prognosis in gastric cancer.
Liu Y et al.·Tumour Biol
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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