WASF1

WASP family member 1, the group of Wiskott-Aldrich Syndrome protein family|A-kinase anchoring proteins|SCAR/WAVE complex

Basic information

Region (hg38): 6:110099818-110180004

Links

ENSG00000112290 ∙ NCBI:8936 ∙ OMIM:605035 ∙ HGNC:12732 ∙ Uniprot:Q92558 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with absent language and variable seizures (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with absent language and variable seizures (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with absent language and variable seizures	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	29961568

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WASF1 gene.

• Neurodevelopmental disorder with absent language and variable seizures (3 variants)
• Intellectual disability (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WASF1 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				6		6
missense		1	34	6	1	42
nonsense	2	2	1			5
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding			2			2
Total	3	3	37	12	1

Variants in WASF1

This is a list of pathogenic ClinVar variants found in the WASF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-110100589-C-T			Uncertain significance (Sep 20, 2022)
6-110100622-A-G		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
6-110100644-G-A		Intellectual disability • Neurodevelopmental disorder with absent language and variable seizures • Epileptic encephalopathy	Pathogenic (Dec 20, 2019)
6-110100649-C-T			Uncertain significance (Mar 31, 2022)
6-110101588-C-T		Neurodevelopmental disorder with absent language and variable seizures	Uncertain significance (Aug 09, 2022)
6-110101594-G-A		Intellectual disability • Neurodevelopmental disorder with absent language and variable seizures	Pathogenic (Mar 26, 2023)
6-110101628-G-CCTGGC		Intellectual disability • Neurodevelopmental disorder with absent language and variable seizures	Pathogenic (Dec 20, 2019)
6-110101636-GT-G		Neurodevelopmental disorder with absent language and variable seizures	Pathogenic (Jul 17, 2023)
6-110101644-G-C		Neurodevelopmental disorder with absent language and variable seizures	Likely pathogenic (Mar 05, 2021)
6-110101651-G-A		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
6-110101674-A-G			Uncertain significance (Mar 15, 2022)
6-110101679-T-G		WASF1-related disorder	Uncertain significance (Jan 10, 2024)
6-110101712-A-C			Likely benign (Nov 01, 2022)
6-110101725-G-A		WASF1-related disorder	Likely benign (Sep 02, 2021)
6-110101728-G-A		WASF1-related disorder	Likely benign (Nov 01, 2023)
6-110101779-G-A			Uncertain significance (Aug 25, 2022)
6-110101791-G-A			Likely pathogenic (Feb 01, 2023)
6-110101841-C-T		WASF1-related disorder	Likely benign (May 31, 2019)
6-110101851-A-C		Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
6-110101913-T-C			Likely benign (Aug 01, 2021)
6-110101926-T-C			Uncertain significance (May 27, 2022)
6-110101957-C-A		Inborn genetic diseases	Uncertain significance (May 25, 2023)
6-110101991-A-C			Likely benign (Jun 01, 2024)
6-110102027-A-T		WASF1-related disorder	Likely benign (May 21, 2019)
6-110102050-G-A		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WASF1	protein_coding	protein_coding	ENST00000392589	8	80186

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00243	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.55	175	299	0.586	0.0000158	3582
Missense in Polyphen		14	44.693	0.31325		504
Synonymous	1.32	88	105	0.836	0.00000545	1186
Loss of Function	4.15	1	22.1	0.0453	0.00000126	267

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: Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF- NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). {ECO:0000250|UniProtKB:Q8R5H6, ECO:0000269|PubMed:9889097}.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Adherens junction - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);VEGFA-VEGFR2 Signaling Pathway;Regulation of Actin Cytoskeleton;Signal Transduction;how does salmonella hijack a cell;VEGFA-VEGFR2 Pathway;rac1 cell motility signaling pathway;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;RHO GTPases Activate WASPs and WAVEs;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of actin dynamics for phagocytic cup formation;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;RAC1 signaling pathway;E2F transcription factor network (Consensus)

Intolerance Scores

• loftool: 0.317
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.680
• hipred: Y
• hipred_score: 0.825
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wasf1
• Phenotype: digestive/alimentary 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: receptor-mediated endocytosis;Rac protein signal transduction;actin filament polymerization;positive regulation of neurotrophin TRK receptor signaling pathway;protein-containing complex assembly;lamellipodium morphogenesis;dendrite extension;modification of postsynaptic actin cytoskeleton;dendritic transport of mitochondrion;cellular response to brain-derived neurotrophic factor stimulus;positive regulation of Arp2/3 complex-mediated actin nucleation
• Cellular component: mitochondrial outer membrane;cytoskeleton;focal adhesion;actin cytoskeleton;lamellipodium;SCAR complex;dendrite cytoplasm;protein-containing complex;postsynapse
• Molecular function: actin binding;protein binding;Rac GTPase binding;protein kinase A binding