UNC13A

unc-13 homolog A, the group of UNC13 homologs

Basic information

Region (hg38): 19:17601336-17688365

Links

ENSG00000130477 ∙ NCBI:23025 ∙ OMIM:609894 ∙ HGNC:23150 ∙ Uniprot:Q9UPW8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital nervous system disorder (Limited), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UNC13A gene.

• not_specified (130 variants)
• UNC13A-related_disorder (124 variants)
• not_provided (103 variants)
• Neurodevelopmental_disorder (3 variants)
• UNC13A-related_Neurodevelopmental_and_Movement_disorder (3 variants)
• Tremor (2 variants)
• Amyotrophic_lateral_sclerosis (2 variants)
• Cerebellar_ataxia (2 variants)
• Amyotrophic_lateral_sclerosis_type_1 (1 variants)
• UNC13A-related_Neurodevelopmental_disorder (1 variants)
• Microcephaly (1 variants)
• Delayed_speech_and_language_development (1 variants)
• UNC13A-associated_disorder (1 variants)
• Febrile_seizure_(within_the_age_range_of_3_months_to_6_years) (1 variants)
• Developmental_regression (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UNC13A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001080421.3. 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				78	12	90
missense		2	185	8	1	196
nonsense			3			3
start loss						0
frameshift	1		9			10
splice donor/acceptor (+/-2bp)			5			5
Total	1	2	202	86	13

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UNC13A	protein_coding	protein_coding	ENST00000519716	44	87265

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.01e-10	125167	0	29	125196	0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.63	513	1.02e+3	0.504	0.0000641	11229
Missense in Polyphen		174	467.09	0.37252		4933
Synonymous	-0.0310	428	427	1.00	0.0000311	3085
Loss of Function	8.39	9	99.1	0.0908	0.00000513	1103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000942	0.000938
Ashkenazi Jewish	0.0000998	0.0000993
East Asian	0.0000556	0.0000545
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000441
Middle Eastern	0.0000556	0.0000545
South Asian	0.0000999	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses (By similarity). Also involved in secretory granule priming in insulin secretion (By similarity). Interacts with FBXO45 (via SRY domain); leading to the degradation of UNC13A by the proteasome (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250, ECO:0000269|PubMed:23999003}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Synaptic Vesicle Pathway (Consensus)

Intolerance Scores

• rvis_EVS: -1.7
• rvis_percentile_EVS: 2.58

Haploinsufficiency Scores

• pHI: 0.207
• hipred: Y
• hipred_score: 0.623
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.875

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Unc13a
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system 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); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: positive regulation of neurotransmitter secretion;neurotransmitter secretion;neuromuscular junction development;synaptic vesicle docking;synaptic vesicle priming;synaptic vesicle maturation;positive regulation of synaptic plasticity;synaptic transmission, glutamatergic;intracellular signal transduction;regulation of short-term neuronal synaptic plasticity;amyloid-beta metabolic process;regulation of synaptic transmission, glutamatergic;innervation;dense core granule priming;presynaptic dense core vesicle exocytosis;positive regulation of glutamate receptor signaling pathway;regulation of amyloid precursor protein catabolic process;positive regulation of dendrite extension
• Cellular component: plasma membrane;cell junction;synaptic vesicle membrane;neuromuscular junction;presynaptic membrane;neuron projection;terminal bouton;calyx of Held;presynaptic active zone;presynaptic active zone cytoplasmic component;glutamatergic synapse
• Molecular function: calcium ion binding;calmodulin binding;phospholipid binding;syntaxin-1 binding;diacylglycerol binding