SLC32A1

protein-coding

solute carrier family 32 member 1, the group of Solute carrier family 32

Gene summary

The protein encoded by this gene is an integral membrane protein involved in gamma-aminobutyric acid (GABA) and glycine uptake into synaptic vesicles. The encoded protein is a member of amino acid/polyamine transporter family II. [provided by RefSeq, Jul 2008]

Previous symbols:

VIAAT

MANE transcript

NM_080552.3

Inheritance

ClinVar variants

P:7U:92B:6

Top phenotype

Generalized epilepsy with febrile seizures plus, type 12; Developmental and epileptic encephalopathy 114

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr20:38,724,486-38,729,372

External References & Databases

Ensembl (ENSG00000101438)

Transcript & Mutation Effects

hg38 • Region Span ~4.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

generalized epilepsy with febrile seizures plus, type 12STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0958324

Submitter: PanelApp Australia

developmental and epileptic encephalopathy 114MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0958331

Submitter: G2P

developmental and epileptic encephalopathy 114STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0958331

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Generalized epilepsy with febrile seizures plus, type 12; Developmental and epileptic encephalopathy 114AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 34038384; 36073542

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC32A1 variants in ClinVar

15 Conditions Cataloged

not providedTotal: 46

Inborn genetic diseasesTotal: 39

Generalized epilepsy with febrile seizures plus, type 12Total: 9

Generalized epilepsy with febrile seizures plusTotal: 8

Intellectual disabilityTotal: 4

SeizureTotal: 4

SLC32A1-related conditionTotal: 3

Developmental and epileptic encephalopathy 114Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080552.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar		5
missense	1 clinvar	6 clinvar	87 clinvar		1 clinvar	95
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	6	92	5	1	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080552.3	RefSeq	NP_542119.1	2	MANE Select
ENST00000217420.2	Ensembl	ENSP00000217420.1	2	MANE Select
ENST00001133273.1	Ensembl	ENSP00000801598.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Benzodiazepine Pathway, Pharmacodynamics
Synaptic vesicle cycle - Homo sapiens (human)
Retrograde endocannabinoid signaling - Homo sapiens (human)
GABAergic synapse - Homo sapiens (human)
Nicotine addiction - Homo sapiens (human)

Biological Process

amino acid transmembrane transport
ion transport
neurotransmitter secretion
aging
gamma-aminobutyric acid transport

Molecular Function

amino acid transmembrane transporter activity
glycine transmembrane transporter activity
gamma-aminobutyric acid:proton symporter activity

Cellular Component

plasma membrane
integral component of synaptic vesicle membrane
dendrite
synaptic vesicle membrane
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217420
Coding exons: 2
Length: 4911
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125732
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.30	188	300	0.626	0.0000141	3404
Missense (PolyPhen)		25	83.639	0.2989		997
Synonymous	-0.425	144	138	1.05	0.00000689	1111
Loss of Function	3.35	1	15.0	0.0668	6.55e-7	154

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the uptake of GABA and glycine into the synaptic vesicles. {ECO:0000250|UniProtKB:O35458}.;

Recessive Scores

pRec: 0.169

Intolerance Scores

LoFtool: 0.123
RVIS EVS: -0.03
RVIS percentile EVS: 51.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.386

Gene Damage Prediction

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