Human Gene Module / Chromosome 2 / NCKAP1

NCKAP1NCK-associated protein 1

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
5 / 0
Aliases
NCKAP1, HEM2,  NAP1,  NAP125,  p125Nap1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
2q32.1
Associated Disorders
-
Relevance to Autism

Two de novo loss-of-function variants in the NCKAP1 gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex.

Reports related to NCKAP1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
2 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
3 Recent recommendation The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
4 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
5 Support The Contribution of Mosaic Variants to Autism Spectrum Disorder. Freed D and Pevsner J (2016) Yes -
6 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3262G>T p.Glu1088Ter stop_gained De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.2321_2322del p.Gln774fs frameshift_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.767A>G p.Arg256Gly missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.503_504insTG p.His168fs frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.3180+1G>A p.? splice_site_variant De novo - - 27824329 Wang T , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo LoF variants in the NCKAP1 gene (one nonsense, one frameshift) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). A third de novo LoF variant in NCKAP1 was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016.

2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

04-01-2017
2

Initial score established: 2

Description

Two de novo LoF variants in the NCKAP1 gene (one nonsense, one frameshift) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). A third de novo LoF variant in NCKAP1 was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016.

CNVs associated with NCKAP1(1 CNVs)
2q32.1 20 Deletion-Duplication 34  /  170
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
AMZ1 Archaemetzincin-1 Human Protein Binding 155185 Q400G9
CGB2 chorionic gonadotropin, beta polypeptide 2 Human Protein Binding 114336 Q6NT52
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