HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NCKAP1
NCK associated protein 1
Chromosome 2 Β· 2q32.1
NCBI Gene: 10787Ensembl: ENSG00000061676.16HGNC: HGNC:7666UniProt: A0A994J4I5
133PubMed Papers
20Diseases
0Drugs
22Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
small GTPase bindingprotein bindingpositive regulation of lamellipodium assemblyRac protein signal transductionneurodegenerative diseaseNeurodevelopmental disordergenetic disorderIntellectual disability
✦AI Summary

NCKAP1 (NCK-associated protein 1) is a cytoskeletal regulatory protein that functions as a core component of the WAVE complex, which regulates actin filament reorganization and lamellipodia formation through interaction with the Arp2/3 complex in a RAC1-dependent manner. In neurons, NCKAP1 is essential for neuronal differentiation and migration during cortical development, with high expression in excitatory neurons and radial glia during prenatal and postnatal periods 1. Disruptive NCKAP1 variants cause a neurodevelopmental disorder characterized by autism spectrum disorder, language and motor delays, and intellectual disability 1. The gene was first identified as markedly depressed in Alzheimer disease brains, with antisense oligonucleotides inducing neuronal apoptosis 2. More recently, NCKAP1 variants have been associated with intellectual disability and epilepsy with absence seizures 3 4. Beyond neurodevelopment, NCKAP1 functions as a tumor suppressor in renal carcinoma. Low NCKAP1 expression correlates with poor prognosis and advanced cancer stage, while NCKAP1 overexpression reduces cancer cell proliferation, invasion, and migration through modulation of the PI3K/AKT/mTOR signaling pathway 5 6. Additionally, NCKAP1 depletion partially rescues glioblastoma cells from disulfidptosis induced by thioredoxin reductase 1 inhibition 7.

Sources cited
1
NCKAP1 regulates neuronal cytoskeletal dynamics, is essential for neuronal differentiation, and disruptive variants cause neurodevelopmental disorder with autism, language/motor delays, and intellectual disability
PMID: 33157009
2
NCKAP1 heterozygous truncating variant identified in large family with autosomal dominant mild intellectual disability with full segregation; candidacy supported by biological function and brain expression
PMID: 28940097
3
NCKAP1 is markedly depressed in Alzheimer disease-affected brains; predominantly expressed in neuronal cells; antisense oligonucleotides induce neuronal cell apoptosis
PMID: 10673335
4
NCKAP1 variants associated with epilepsies with absence seizures as monogenic etiology; previously not associated with this seizure type
PMID: 41137852
5
NCKAP1 suppresses renal cancer cell growth and affects tumor development via PI3K/AKT/mTOR signaling pathway; reduced levels linked to poor patient prognosis
PMID: 40141455
6
Low NCKAP1 expression associated with poor overall survival and disease-free survival in renal clear cell carcinoma; overexpression reduces cell proliferation, invasion, and migration
PMID: 39262720
7
NCKAP1 depletion partially rescues glucose-starved glioblastoma cells from TrxR1 inhibition-induced disulfidptosis
PMID: 39715824
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.53Moderate
Neurodevelopmental disorderOpen Targets
0.47Moderate
genetic disorderOpen Targets
0.45Moderate
Intellectual disabilityOpen Targets
0.44Moderate
Autistic behaviorOpen Targets
0.43Moderate
complex neurodevelopmental disorderOpen Targets
0.40Weak
autismOpen Targets
0.37Weak
Neurodevelopmental abnormalityOpen Targets
0.34Weak
Global developmental delayOpen Targets
0.33Weak
immunodeficiency 72 with autoinflammationOpen Targets
0.27Weak
muscular diseaseOpen Targets
0.24Weak
autism spectrum disorderOpen Targets
0.12Weak
Focal sensory seizure with somatosensory featuresOpen Targets
0.12Weak
placental retentionOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Weak
cancerOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
kidney neoplasmOpen Targets
0.07Suggestive
Pathogenic Variants22
NM_013436.5(NCKAP1):c.2392C>T (p.Arg798Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 798
NM_013436.5(NCKAP1):c.2113C>T (p.Arg705Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 705
NM_013436.5(NCKAP1):c.3118_3127del (p.Ala1040fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1040
NM_013436.5(NCKAP1):c.1004+1G>APathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025
NM_013436.5(NCKAP1):c.883_886del (p.Leu295fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 295
NM_013436.5(NCKAP1):c.2111del (p.Pro704fs)Pathogenic
NCKAP1-associated Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 704
NM_013436.5(NCKAP1):c.634del (p.Met212fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 212
NM_013436.5(NCKAP1):c.790+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_013436.5(NCKAP1):c.885_886del (p.Phe296fs)Likely pathogenic
NCKAP1-related neurodevelopmental disorder with autism features
β˜…β˜†β˜†β˜†2024β†’ Residue 296
NM_013436.5(NCKAP1):c.922G>A (p.Glu308Lys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 308
NM_013436.5(NCKAP1):c.1488T>G (p.Tyr496Ter)Pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 496
NM_013436.5(NCKAP1):c.2007G>T (p.Arg669Ser)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 669
NM_013436.5(NCKAP1):c.2226T>G (p.Ser742Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 742
NM_013436.5(NCKAP1):c.2749C>T (p.Arg917Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 917
NM_013436.5(NCKAP1):c.3280G>T (p.Glu1094Ter)Likely pathogenic
Immunodeficiency 72 with autoinflammation
β˜…β˜†β˜†β˜†2024β†’ Residue 1094
NM_013436.5(NCKAP1):c.1861C>T (p.Gln621Ter)Pathogenic
Neurodevelopmental abnormality;Autistic behavior
β˜…β˜†β˜†β˜†2023β†’ Residue 621
NM_013436.5(NCKAP1):c.3165_3176del (p.Lys1056_Leu1059del)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 1056
NM_013436.5(NCKAP1):c.155del (p.Asn52fs)Likely pathogenic
Intellectual disability
β˜…β˜†β˜†β˜†2022β†’ Residue 52
NM_013436.5(NCKAP1):c.684_687del (p.Gln228fs)Likely pathogenic
NCKAP1-associated Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2021β†’ Residue 228
NM_013436.5(NCKAP1):c.778A>T (p.Lys260Ter)Likely pathogenic
Global developmental delay
β˜…β˜†β˜†β˜†2019β†’ Residue 260
View on ClinVar β†—
Related Genes
CDC42Protein interaction100%SRA1Protein interaction99%ABI3Protein interaction99%ELMO2Protein interaction97%RAC2Protein interaction96%ARF1Protein interaction94%
Tissue Expression6 tissues
Heart
100%
Brain
78%
Ovary
39%
Lung
35%
Liver
29%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
NCKAP1CDC42SRA1ABI3ELMO2RAC2ARF1
PROTEIN STRUCTURE
Preparing viewer…
PDB3P8C Β· 2.29 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.14Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.07 [0.04–0.14]
RankingsWhere NCKAP1 stands among ~20K protein-coding genes
  • #3,491of 20,598
    Most Researched133 Β· top quartile
  • #2,096of 5,498
    Most Pathogenic Variants22
  • #169of 17,882
    Most Constrained (LOEUF)0.14 Β· top 1%
Genes detectedNCKAP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Expanding the genetic heterogeneity of intellectual disability.
PMID: 28940097
Hum Genet Β· 2017
1.00
2
NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism.
PMID: 33157009
Am J Hum Genet Β· 2020
0.90
3
Rapid identification of primary atopic disorders (PAD) by a clinical landmark-guided, upfront use of genomic sequencing.
PMID: 39381601
Allergol Select Β· 2024
0.80
4
Inhibition of thioredoxin reductase 1 sensitizes glucose-starved glioblastoma cells to disulfidptosis.
PMID: 39715824
Cell Death Differ Β· 2025
0.70
5
Molecular cloning of a novel apoptosis-related gene, human Nap1 (NCKAP1), and its possible relation to Alzheimer disease.
PMID: 10673335
Genomics Β· 2000
0.60