SLC18A3

solute carrier family 18 member A3, the group of Solute carrier family 18

Basic information

Region (hg38): 10:49610309-49612720

Links

ENSG00000187714 ∙ NCBI:6572 ∙ OMIM:600336 ∙ HGNC:10936 ∙ Uniprot:Q16572 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 21 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 21 (Strong), mode of inheritance: AR
• fetal akinesia deformation sequence 1 (Supportive), mode of inheritance: AR
• presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD
• congenital myasthenic syndrome 21 (Limited), mode of inheritance: AR
• congenital myasthenic syndrome 21 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 21, presynaptic	AR	Musculoskeletal	Early diagnosis and management has been described as beneficial, as individuals have been reported as responding to medical management (with pyridostigmine)	Musculoskeletal	27590285

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC18A3 gene.

• not provided (203 variants)
• Inborn genetic diseases (22 variants)
• Congenital myasthenic syndrome 21 (8 variants)
• Familial infantile myasthenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC18A3 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			2	78	7	87
missense		2	116	4	4	126
nonsense		1				1
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	4	119	82	12

Variants in SLC18A3

This is a list of pathogenic ClinVar variants found in the SLC18A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-49610749-C-T			Likely benign (Jun 08, 2022)
10-49610751-C-G			Uncertain significance (Jul 13, 2022)
10-49610752-G-A			Likely benign (Aug 28, 2023)
10-49610772-G-A			Likely benign (Nov 01, 2023)
10-49610772-G-T			Uncertain significance (Jul 05, 2022)
10-49610774-GC-AG			Uncertain significance (Sep 07, 2022)
10-49610776-G-A			Likely benign (Oct 27, 2022)
10-49610777-G-C			Benign (Jan 29, 2024)
10-49610779-G-A			Likely benign (Jan 29, 2024)
10-49610781-C-A		Inborn genetic diseases	Uncertain significance (Mar 13, 2023)
10-49610781-C-T			Benign (Dec 30, 2023)
10-49610786-A-G			Uncertain significance (Oct 26, 2021)
10-49610804-G-A			Uncertain significance (Nov 30, 2021)
10-49610825-C-T		Congenital myasthenic syndrome 21 • SLC18A3-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
10-49610828-C-A		CHAT-related disorder	Benign (Jan 29, 2024)
10-49610828-C-T		Congenital myasthenic syndrome 21	Uncertain significance (Aug 23, 2022)
10-49610830-G-A			Likely benign (Sep 01, 2022)
10-49610848-T-A			Likely benign (Apr 06, 2022)
10-49610850-T-C			Uncertain significance (Sep 21, 2021)
10-49610852-A-T			Uncertain significance (Sep 21, 2021)
10-49610854-C-T			Likely benign (Sep 06, 2022)
10-49610877-A-G			Uncertain significance (Mar 18, 2022)
10-49610891-A-G		Congenital myasthenic syndrome 21	Uncertain significance (Mar 02, 2018)
10-49610915-G-A		Inborn genetic diseases	Uncertain significance (May 18, 2022)
10-49610917-C-G			Uncertain significance (Jul 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC18A3	protein_coding	protein_coding	ENST00000374115	1	2419

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.454	0.541	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.145	311	318	0.977	0.0000151	3292
Missense in Polyphen		112	131.78	0.84989		1433
Synonymous	-2.63	190	149	1.27	0.00000768	1236
Loss of Function	2.33	2	9.90	0.202	4.26e-7	108

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: Involved in acetylcholine transport into synaptic vesicles. {ECO:0000269|PubMed:8071310}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction);Synaptic Vesicle Pathway;Vesicle-mediated transport;Membrane Trafficking;Neuronal System;Glycerophospholipid metabolism;Clathrin-mediated endocytosis;Acetylcholine Neurotransmitter Release Cycle;Neurotransmitter release cycle;Cargo recognition for clathrin-mediated endocytosis;Transmission across Chemical Synapses (Consensus)

Intolerance Scores

• loftool: 0.523
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.58

Haploinsufficiency Scores

• pHI: 0.213
• hipred: N
• hipred_score: 0.445
• ghis: 0.457

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.571

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc18a3
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; skeleton 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)

Gene ontology

• Biological process: drug transmembrane transport;neurotransmitter secretion;organic cation transport;membrane organization;ammonium transmembrane transport;acetate ester transport
• Cellular component: plasma membrane;integral component of membrane;AP-1 adaptor complex;AP-2 adaptor complex;clathrin-coated vesicle membrane;terminal bouton;clathrin-sculpted acetylcholine transport vesicle membrane
• Molecular function: acetylcholine transmembrane transporter activity