VAC14

VAC14 component of PIKFYVE complex, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 16:70687439-70801160

Previous symbols: [ "TAX1BP2" ]

Links

ENSG00000103043 ∙ NCBI:55697 ∙ OMIM:604632 ∙ HGNC:25507 ∙ Uniprot:Q08AM6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• striatonigral degeneration, childhood-onset (Moderate), mode of inheritance: AR
• hereditary neurological disease (Moderate), mode of inheritance: AR
• striatonigral degeneration, childhood-onset (Strong), mode of inheritance: AR
• Yunis-Varon syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Striatonigral degeneration, childhood-onset	AR	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	Neurologic	27292112

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VAC14 gene.

• not_provided (407 variants)
• Inborn_genetic_diseases (104 variants)
• Striatonigral_degeneration,_childhood-onset (19 variants)
• VAC14-related_disorder (12 variants)
• Yunis-Varon_syndrome (2 variants)
• Neurodegeneration (1 variants)
• Myoepithelial_tumor (1 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAC14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018052.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	147	8	156
missense	3	3	166	6	3	181
nonsense	1	1	1			3
start loss						0
frameshift	4	1	1			6
splice donor/acceptor (+/-2bp)	2	3	10			15
Total	10	8	179	153	11

Highest pathogenic variant AF is 0.000018587107

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAC14	protein_coding	protein_coding	ENST00000261776	19	113723

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.17	335	467	0.717	0.0000278	5100
Missense in Polyphen		108	176.51	0.61185		1927
Synonymous	-0.974	228	210	1.09	0.0000134	1574
Loss of Function	4.29	9	37.3	0.241	0.00000167	444

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000607	0.0000607
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000172	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000178	0.000176
Middle Eastern	0.000172	0.000163
South Asian	0.000198	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts as a positive activator of PIKfyve kinase activity. Also required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. {ECO:0000269|PubMed:15542851, ECO:0000269|PubMed:17556371}.
• Disease: DISEASE: Striatonigral degeneration, childhood-onset (SNDC) [MIM:617054]: An autosomal recessive neurological disorder characterized by sudden childhood onset of developmental regression. Affected children develop impaired movements with dystonia, progressively become non-ambulatory and non-verbal, and exhibit striatal abnormalities on MRI. {ECO:0000269|PubMed:27292112}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HTLV-I infection - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;Metabolism of lipids;Metabolism;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the late endosome membrane;PI Metabolism;Phospholipid metabolism (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.223
• rvis_EVS: -1.15
• rvis_percentile_EVS: 6.29

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.799

Gene Damage Prediction

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

Gene ontology

• Biological process: phosphatidylinositol biosynthetic process;signal transduction;viral process
• Cellular component: Golgi membrane;extrinsic component of vacuolar membrane;endoplasmic reticulum;endosome membrane;early endosome membrane;late endosome membrane;PAS complex
• Molecular function: protein binding;signaling receptor activity