UNC13A unc-13 homolog A [Homo sapiens (human)] - Gene

Summary

Official Symbol: UNC13Aprovided by HGNC
Official Full Name: unc-13 homolog Aprovided by HGNC
Primary source: HGNC:HGNC:23150
See related: Ensembl:ENSG00000130477 MIM:609894; AllianceGenome:HGNC:23150
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: Munc13-1
Summary: This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]
Expression: Biased expression in brain (RPKM 22.6), adrenal (RPKM 1.5) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.11

Exon count:: 44

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (17601336..17688354, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (17735579..17822489, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (17712145..17799163, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease.
Title: Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease.
Interaction of the C9orf72-Amyotrophic Lateral Sclerosis-Related Proline-Arginine Dipeptide Repeat Protein with the RNA-Binding Protein NOVA1 Causes Decreased Expression of UNC13A Due to Enhanced Inclusion of Cryptic Exons, Which Is Reversed by Betulin Treatment.
Title: Interaction of the C9orf72-Amyotrophic Lateral Sclerosis-Related Proline-Arginine Dipeptide Repeat Protein with the RNA-Binding Protein NOVA1 Causes Decreased Expression of UNC13A Due to Enhanced Inclusion of Cryptic Exons, Which Is Reversed by Betulin Treatment.
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.
Title: TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.
TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A.
Title: TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A.
Probing the Diacylglycerol Binding Site of Presynaptic Munc13-1.
Title: Probing the Diacylglycerol Binding Site of Presynaptic Munc13-1.
The Distinct Traits of the UNC13A Polymorphism in Amyotrophic Lateral Sclerosis.
Title: The Distinct Traits of the UNC13A Polymorphism in Amyotrophic Lateral Sclerosis.
rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.
Title: UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis.
Its polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis.
Title: UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis.
This study demonstrated that the population specific rare variants of UNC13A may modulate survival in ALS in United kingdom.
Title: Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis.
Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder
Title: Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1. EBI GWAS Catalog EBI GWAS CatalogPubMed
C9orf72 and UNC13A are shared risk loci for ALS and FTD: A genome-wide meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

D1S1423 (e-PCR)
- UniSTS:149619

RH15984 (e-PCR)
- UniSTS:93067

SHGC-89041 (e-PCR)
- UniSTS:104898

G20690 (e-PCR)
- UniSTS:16075

A006C03 (e-PCR)
- UniSTS:16076

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	ISS Inferred from Sequence or Structural Similarity more info
enables diacylglycerol binding	IEA Inferred from Electronic Annotation more info
enables phospholipid binding	IEA Inferred from Electronic Annotation more info
enables syntaxin-1 binding	IBA Inferred from Biological aspect of Ancestor more info
enables syntaxin-1 binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in dense core granule priming	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuronal dense core vesicle exocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in neurotransmitter secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of dendrite extension	IDA Inferred from Direct Assay more info	PubMed
involved_in presynaptic dense core vesicle exocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of synaptic transmission, glutamatergic	TAS Traceable Author Statement more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic vesicle docking	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic vesicle priming	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in neuromuscular junction	IBA Inferred from Biological aspect of Ancestor more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in presynaptic active zone	TAS Traceable Author Statement more info	PubMed
is_active_in presynaptic active zone cytoplasmic component	IBA Inferred from Biological aspect of Ancestor more info
is_active_in presynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in presynaptic membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in synaptic vesicle membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in terminal bouton	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: protein unc-13 homolog A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052872.1 RefSeqGene

Range

4991..92009

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001080421.3 → NP_001073890.2 protein unc-13 homolog A isoform 1

See identical proteins and their annotated locations for NP_001073890.2

Status: REVIEWED

Source sequence(s)

AC008761

Consensus CDS

CCDS46013.2

UniProtKB/Swiss-Prot

E5RHY9, Q9UPW8

UniProtKB/TrEMBL

F8W059

Related

ENSP00000429562.2, ENST00000519716.7

Conserved Domains (6) summary

cd04027
Location:676 → 802

C2B_Munc13; C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins

cd08394
Location:1 → 127

C2A_Munc13; C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins

cd08395
Location:1546 → 1665

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:554 → 603

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:994 → 1102

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1347 → 1508

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
NM_001387021.1 → NP_001373950.1 protein unc-13 homolog A isoform 2

Status: REVIEWED

Source sequence(s)

AC008761

UniProtKB/TrEMBL

F8W059

Conserved Domains (6) summary

cd04027
Location:674 → 800

C2B_Munc13; C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins

cd08394
Location:1 → 127

C2A_Munc13; C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins

cd08395
Location:1542 → 1661

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

pfam06292
Location:992 → 1100

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1344 → 1504

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain

cd20859
Location:533 → 614

C1_Munc13-2-like; protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins
NM_001387022.1 → NP_001373951.1 protein unc-13 homolog A isoform 3

Status: REVIEWED

Source sequence(s)

AC008761

UniProtKB/TrEMBL

F8W059

Conserved Domains (6) summary

cd04027
Location:674 → 800

C2B_Munc13; C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins

cd08394
Location:1 → 127

C2A_Munc13; C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins

cd08395
Location:1541 → 1660

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

pfam06292
Location:992 → 1100

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1343 → 1503

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain

cd20859
Location:533 → 614

C1_Munc13-2-like; protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins
NM_001387023.1 → NP_001373952.1 protein unc-13 homolog A isoform 4

Status: REVIEWED

Source sequence(s)

AC008761

Consensus CDS

CCDS92557.1

UniProtKB/TrEMBL

F8VZH8, F8W0P6

Related

ENSP00000446831.1, ENST00000550896.1

Conserved Domains (6) summary

cd04027
Location:674 → 800

C2B_Munc13; C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins

cd08394
Location:1 → 127

C2A_Munc13; C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins

cd08395
Location:1519 → 1638

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

pfam06292
Location:992 → 1100

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1344 → 1481

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain

cd20859
Location:533 → 614

C1_Munc13-2-like; protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

17601336..17688354 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011527810.3 → XP_011526112.1 protein unc-13 homolog A isoform X2

UniProtKB/TrEMBL

F8W059

Conserved Domains (6) summary

cd04027
Location:666 → 792

C2B_Munc13; C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins

cd08394
Location:1 → 117

C2A_Munc13; C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins

cd08395
Location:1536 → 1655

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:544 → 593

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:984 → 1092

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1337 → 1498

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
XM_017026502.2 → XP_016881991.1 protein unc-13 homolog A isoform X1

UniProtKB/TrEMBL

F8W059
XM_011527811.3 → XP_011526113.1 protein unc-13 homolog A isoform X3

UniProtKB/TrEMBL

F8W0P6

Related

ENSP00000447572.1, ENST00000552293.5

Conserved Domains (6) summary

cd04027
Location:676 → 802

C2B_Munc13; C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins

cd08394
Location:1 → 127

C2A_Munc13; C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins

cd08395
Location:1523 → 1642

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:554 → 603

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:994 → 1102

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1347 → 1485

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain