NCKAP1

NCK associated protein 1, the group of SCAR/WAVE complex

Basic information

Region (hg38): 2:182909114-183038858

Links

ENSG00000061676 ∙ NCBI:10787 ∙ OMIM:604891 ∙ HGNC:7666 ∙ Uniprot:Q9Y2A7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCKAP1 gene.

• not provided (47 variants)
• Inborn genetic diseases (17 variants)
• NCKAP1-related condition (3 variants)
• Neurodevelopmental disorder (2 variants)
• Global developmental delay (1 variants)
• not specified (1 variants)
• Autistic behavior;Neurodevelopmental abnormality (1 variants)
• Complex neurodevelopmental disorder (1 variants)
• NCKAP1-associated Neurodevelopmental disorder (1 variants)
• Intellectual disability (1 variants)
• Neurodevelopmental disorder;Autism spectrum disorder;Focal sensory seizure with somatosensory features (1 variants)
• Autistic behavior (1 variants)
• NCKAP1-Related Disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCKAP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			56	1		57
nonsense	2	1				3
start loss						0
frameshift	1	2	2			5
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)			1			1
splice region			1		2	3
non coding			2		1	3
Total	3	4	62	4	1

Variants in NCKAP1

This is a list of pathogenic ClinVar variants found in the NCKAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-182925715-G-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
2-182925737-CATGG-C		Neurodevelopmental disorder;Autism spectrum disorder;Focal sensory seizure with somatosensory features	Uncertain significance (Aug 26, 2021)
2-182925739-T-TGGTATG			Uncertain significance (Nov 29, 2022)
2-182925743-A-T			Uncertain significance (Jan 27, 2022)
2-182925809-C-A		Immunodeficiency 72 with autoinflammation	Likely pathogenic (Mar 17, 2024)
2-182926844-CTA-C		Autistic behavior	Pathogenic (-)
2-182928117-C-T			Uncertain significance (Jul 26, 2022)
2-182928120-CAGAAATTCTTTA-C		Inborn genetic diseases	Likely pathogenic (May 09, 2023)
2-182928135-A-G			Likely benign (Aug 01, 2022)
2-182928136-C-T		Inborn genetic diseases	Uncertain significance (May 26, 2022)
2-182928216-G-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
2-182930754-G-A			Uncertain significance (Apr 19, 2022)
2-182930765-T-C		NCKAP1-related disorder	Likely benign (Jul 29, 2019)
2-182930783-T-C			Likely benign (Feb 01, 2024)
2-182930792-A-AT		NCKAP1-related disorder	Likely benign (Sep 10, 2019)
2-182934795-A-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
2-182934796-T-C		NCKAP1-related disorder	Likely benign (Jun 14, 2022)
2-182934830-G-C		NCKAP1-related disorder	Benign (Jan 31, 2021)
2-182935304-C-T			Uncertain significance (Jul 26, 2022)
2-182935332-A-G			Likely benign (Jan 01, 2024)
2-182935369-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
2-182935373-C-T			Uncertain significance (Jan 26, 2022)
2-182942166-A-T		Inborn genetic diseases	Uncertain significance (Dec 29, 2023)
2-182952819-T-C		NCKAP1-related disorder	Uncertain significance (Dec 08, 2023)
2-182952858-G-C			Uncertain significance (Jun 24, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCKAP1	protein_coding	protein_coding	ENST00000360982	32	129744

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.15e-11	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.27	291	581	0.501	0.0000287	7483
Missense in Polyphen		56	154.07	0.36346		2017
Synonymous	0.221	194	198	0.980	0.00000984	2051
Loss of Function	7.60	0	67.2	0.00	0.00000352	850

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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}.
• Pathway: Regulation of actin cytoskeleton - Homo sapiens (human);Exercise-induced Circadian Regulation;Regulation of Actin Cytoskeleton;Signal Transduction;VEGFA-VEGFR2 Pathway;y branching of actin filaments;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;RHO GTPases Activate WASPs and WAVEs;RHO GTPase Effectors;Signaling by Rho GTPases;ErbB1 downstream signaling;Regulation of actin dynamics for phagocytic cup formation;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;Stabilization and expansion of the E-cadherin adherens junction;RAC1 signaling pathway;PDGFR-beta signaling pathway;E-cadherin signaling in the nascent adherens junction (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.0326
• rvis_EVS: -1.2
• rvis_percentile_EVS: 5.76

Haploinsufficiency Scores

• pHI: 0.531
• hipred: Y
• hipred_score: 0.809
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nckap1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: nckap1
• Affected structure: CaP motoneuron
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: cell morphogenesis;apoptotic process;central nervous system development;positive regulation of lamellipodium assembly;viral process;cell migration;Rac protein signal transduction;cell projection assembly;positive regulation of actin filament polymerization;cortical actin cytoskeleton organization;Fc-gamma receptor signaling pathway involved in phagocytosis;vascular endothelial growth factor receptor signaling pathway;neuron projection morphogenesis;positive regulation of Arp2/3 complex-mediated actin nucleation
• Cellular component: ruffle;cytosol;focal adhesion;integral component of membrane;lamellipodium;SCAR complex;lamellipodium membrane;filamentous actin;extracellular exosome
• Molecular function: protein binding;Rac GTPase binding