NCKAP1
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
NCKAP1 (HGNC:7666) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
NCK associated protein 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
Nap1, HEM2, NAP125
%HI
9.37(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.14(Read more about gnomAD LOEUF score)
Cytoband
2q32.1
Genomic Coordinates
GRCh37/hg19: chr2:183773843-183903185 NCBI Ensembl UCSC
GRCh38/hg38: chr2:182909115-183038457 NCBI Ensembl UCSC
MANE Select Transcript
NM_013436.5 ENST00000361354.9 (Read more about MANE Select)
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. Actin remodeling activity is regulated by RAC1. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes. {ECO:0000250|UniProtKB:P28660}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-19141
ClinGen Curation ID:
CCID:007524
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
12/27/2017

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Complex Neurodevelopmental Disorder Monarch
HI Evidence:
  • PUBMED: 27632392
    Freed and Pevsner (2016) reported a de novo (potentially mosaic) frameshift variant (NM_205842.2:c.524_525insGT/p.Ala176X) in a patient with autism spectrum disorder.
  • PUBMED: 27824329
    Wang et al., (2016) detected a de novo splicing variant c.3180+ 1G>A in a Chinese patient with ASD and global developmental delay among 1,543 probands with ASD.
  • PUBMED: 28940097
    Anazi et al. (2017) reported a heterozygous nonsense variant c.3298G>T:p.Glu1100* segregated with intellectual disability in a large multigenerational family in an effort for discovering novel genetic causes of intellectual disability. This four generation pedigree had a total of 13 affected (not all were genotyped). Seven heterzygous carriers that were genotyped were all affected. Two unaffected individuals had normal genotype. The gene expression pattern suppport the involvement of NCKAP1 in brain function.
HI Evidence Comments:
This gene is extremely constrained against haploinsufficency in the human genome. Currently at least three independent null variants had been reported in patients with developmental delay (DD), autism spectrum disorder (ASD) and/or intellectual disability (ID). Multiple patients with large deletion involving this gene (and many other genes) exhibited DD/ID/ASD. No deletion involving NCKAP1 was reported in normal populations.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence suggesting triplosensitivity of NCKAP1 gene.

Genomic View

Select assembly: (NC_000002.11) (NC_000002.12)