SLC32A1

Summary

SLC32A1 (solute carrier family 32 member 1, HGNC:11018) is a protein-coding gene on chromosome 20q11.23, encoding Vesicular inhibitory amino acid transporter (Q9H598). Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals.

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.

Source: NCBI Gene 140679 — RefSeq curated summary.

At a glance

• Gene–disease (curated): generalized epilepsy with febrile seizures plus, type 12 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 95 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 112
• MANE Select transcript: NM_080552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11018
Approved symbol	SLC32A1
Name	solute carrier family 32 member 1
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	VGAT, bA122O1.1
Ensembl gene	ENSG00000101438
Ensembl biotype	protein_coding
OMIM	616440
Entrez	140679

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000217420

RefSeq mRNA: 1 — MANE Select: NM_080552 NM_080552

CCDS: CCDS13307

Canonical transcript exons

ENST00000217420 — 2 exons

Exon	Start	End
ENSE00000661971	38724486	38725114
ENSE00000844671	38727452	38729372

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 89.72.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8552 / max 220.3503, expressed in 448 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184583	0.9474	111
184580	0.8364	101
184584	0.5063	273
184582	0.3518	89
184581	0.2134	63

Top tissues by expression

235 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	89.72	gold quality
putamen	UBERON:0001874	85.84	gold quality
prefrontal cortex	UBERON:0000451	85.32	gold quality
caudate nucleus	UBERON:0001873	85.25	gold quality
endothelial cell	CL:0000115	84.10	gold quality
lateral globus pallidus	UBERON:0002476	81.14	gold quality
frontal cortex	UBERON:0001870	80.23	gold quality
neocortex	UBERON:0001950	79.37	gold quality
anterior cingulate cortex	UBERON:0009835	79.25	gold quality
middle temporal gyrus	UBERON:0002771	79.13	gold quality
right frontal lobe	UBERON:0002810	79.09	gold quality
hypothalamus	UBERON:0001898	78.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.03	gold quality
primary visual cortex	UBERON:0002436	78.02	gold quality
forebrain	UBERON:0001890	76.84	gold quality
cerebellar vermis	UBERON:0004720	76.34	gold quality
cerebral cortex	UBERON:0000956	75.50	gold quality
brain	UBERON:0000955	75.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.25	gold quality
occipital lobe	UBERON:0002021	75.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.09	gold quality
Brodmann (1909) area 46	UBERON:0006483	72.68	gold quality
pituitary gland	UBERON:0000007	72.03	gold quality
cerebellum	UBERON:0002037	71.25	gold quality
cerebellar cortex	UBERON:0002129	71.06	gold quality
cerebellar hemisphere	UBERON:0002245	70.78	gold quality
adenohypophysis	UBERON:0002196	70.43	gold quality
amygdala	UBERON:0001876	70.32	gold quality
superior frontal gyrus	UBERON:0002661	70.05	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	26.17
E-GEOD-93593	yes	19.91
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting SLC32A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-6818-3P	98.56	68.23	1307

Literature-anchored findings (GeneRIF, showing 5)

• VIATT has been identified in horizontal cells of the adult outer retina in culture, either at their terminals or throughout the entire cell. (PMID:12115694)
• Subjects with schizophrenia exhibited expression deficits in GABA transpter 1. (PMID:17471287)
• We examined the ratio of excitatory to inhibitory vesicular neurotransmitter transporter mRNAs (VGluT1 to VGAT) and their ratio in the dorsolateral prefrontal cortex during normal human development and in people with schizophrenia (PMID:21396926)
• Data indicate that GABAergic axons were labeled with vesicular inhibitory aa transporter (VIAAT) antibodies, whereas glutamatergic axons were detected with antisera against the major vesicular glutamate transporter (VGLUT) isoforms, VGLUT1 and VGLUT2. (PMID:22510271)
• Association of SLC32A1 Missense Variants With Genetic Epilepsy With Febrile Seizures Plus. (PMID:34038384)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc32a1	ENSDARG00000059775
mus_musculus	Slc32a1	ENSMUSG00000037771
rattus_norvegicus	Slc32a1	ENSRNOG00000015393
drosophila_melanogaster	CG16700	FBGN0030816
drosophila_melanogaster	CG4991	FBGN0030817
drosophila_melanogaster	CG13384	FBGN0032036
drosophila_melanogaster	polyph	FBGN0033572
drosophila_melanogaster	VGAT	FBGN0033911
drosophila_melanogaster	acs	FBGN0035300
drosophila_melanogaster	CG7888	FBGN0036116
drosophila_melanogaster	CG32079	FBGN0052079
drosophila_melanogaster	CG32081	FBGN0052081
drosophila_melanogaster	mah	FBGN0285912
caenorhabditis_elegans		WBGENE00006783
caenorhabditis_elegans	slc-36.4	WBGENE00010421
caenorhabditis_elegans	Y18D10A.23	WBGENE00012487
caenorhabditis_elegans		WBGENE00012629
caenorhabditis_elegans		WBGENE00012804
caenorhabditis_elegans		WBGENE00019837
caenorhabditis_elegans		WBGENE00020837

Paralogs (15): SLC38A5 (ENSG00000017483), SLC38A7 (ENSG00000103042), SLC38A1 (ENSG00000111371), SLC36A1 (ENSG00000123643), SLC38A2 (ENSG00000134294), SLC38A4 (ENSG00000139209), SLC38A6 (ENSG00000139974), SLC38A10 (ENSG00000157637), SLC38A8 (ENSG00000166558), SLC38A11 (ENSG00000169507), SLC38A9 (ENSG00000177058), SLC36A4 (ENSG00000180773), SLC36A3 (ENSG00000186334), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Vesicular inhibitory amino acid transporter — Q9H598 (reviewed: Q9H598)

Alternative names: GABA and glycine transporter, Solute carrier family 32 member 1, Vesicular GABA transporter

All UniProt accessions (1): Q9H598

UniProt curated annotations — full annotation on UniProt →

Function. Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals. The transport is equally dependent on the chemical and electrical components of the proton gradient. May also transport beta-alanine. Acidification of GABAergic synaptic vesicles is a prerequisite for 4-aminobutanoate uptake.

Subcellular location. Cytoplasmic vesicle membrane. Presynapse.

Tissue specificity. Retina. Expressed throughout the horizontal cells or more specifically at the terminals.

Disease relevance. Generalized epilepsy with febrile seizures plus 12 (GEFSP12) [MIM:620755] An autosomal dominant neurologic disorder with variable expressivity and incomplete penetrance. Affected individuals have variable types of seizures, most often febrile seizures, sometimes combined with non-febrile focal or generalized seizures. Rarely, afebrile tonic-clonic seizures have been observed. The disease may be caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 114 (DEE114) [MIM:620774] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE114 is an autosomal dominant form characterized by moderate-to-severe intellectual disability, onset of epilepsy within the first 18 months of life, and a choreiform, dystonic or dyskinetic movement disorder. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the amino acid/polyamine transporter 2 family.

RefSeq proteins (1): NP_542119* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 3 shown:

• 4-aminobutanoate(out) + n H(+)(in) = 4-aminobutanoate(in) + n H(+)(out) (RHEA:70979)
• glycine(out) + n H(+)(in) = glycine(in) + n H(+)(out) (RHEA:70983)
• beta-alanine(out) + n H(+)(in) = beta-alanine(in) + n H(+)(out) (RHEA:70987)

UniProt features (36 total): sequence variant 13, topological domain 10, transmembrane region 9, chain 1, region of interest 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H598-F1	78.69	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 186

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-888590	GABA synthesis, release, reuptake and degradation
R-HSA-425393

MSigDB gene sets: 383 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOCC_CELL_SURFACE, GOBP_NEUROTRANSMITTER_TRANSPORT, MEF2_02, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_HIPPOCAMPUS_DEVELOPMENT, GOCC_COATED_VESICLE, GOBP_PALLIUM_DEVELOPMENT, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT

GO Biological Process (11): beta-alanine transport (GO:0001762), monoatomic ion transport (GO:0006811), neurotransmitter secretion (GO:0007269), gamma-aminobutyric acid transport (GO:0015812), glycine transport (GO:0015816), hippocampus development (GO:0021766), gamma-aminobutyric acid import (GO:0051939), neurotransmitter loading into synaptic vesicle (GO:0098700), amino acid transmembrane transport (GO:0003333), neurotransmitter transport (GO:0006836), proton transmembrane transport (GO:1902600)

GO Molecular Function (6): amino acid transmembrane transporter activity (GO:0015171), gamma-aminobutyric acid transmembrane transporter activity (GO:0015185), glycine transmembrane transporter activity (GO:0015187), gamma-aminobutyric acid:proton symporter activity (GO:0015495), glycine:proton antiporter activity (GO:0140799), gamma-aminobutyric acid:proton antiporter activity (GO:0140800)

GO Cellular Component (20): plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), cell surface (GO:0009986), dendrite (GO:0030425), synaptic vesicle membrane (GO:0030672), neuron projection (GO:0043005), dendrite terminus (GO:0044292), neuron projection terminus (GO:0044306), cone cell pedicle (GO:0044316), presynaptic active zone (GO:0048786), cell tip (GO:0051286), inhibitory synapse (GO:0060077), clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane (GO:0061202), presynapse (GO:0098793), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Neurotransmitter release cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
carboxylic acid transport	3
nitrogen compound transport	3
presynapse	3
synapse	3
neutral amino acid transport	2
transport	2
neurotransmitter transport	2
establishment of localization in cell	2
amino acid transport	2
gamma-aminobutyric acid transport	2
carboxylic acid transmembrane transporter activity	2
gamma-aminobutyric acid transmembrane transporter activity	2
secondary active monocarboxylate transmembrane transporter activity	2
proton transmembrane transporter activity	2
amino acid:monoatomic cation antiporter activity	2
neuron projection	2
chemical synaptic transmission	1
signal release from synapse	1
pallium development	1
limbic system development	1
anatomical structure development	1
acidic amino acid transport	1
intercellular transport	1
synaptic vesicle cycle	1
transmembrane transport	1
monoatomic cation transmembrane transport	1
amino acid transmembrane transport	1
transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
neutral L-amino acid transmembrane transporter activity	1
glycine transport	1
amino acid:proton symporter activity	1
glycine transmembrane transporter activity	1
membrane	1
cell periphery	1
exocytic vesicle	1
dendritic tree	1
synaptic vesicle	1
exocytic vesicle membrane	1

Protein interactions and networks

STRING

3206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC32A1	GAD2	Q05329	967
SLC32A1	SLC17A7	Q9P2U7	960
SLC32A1	GAD1	Q99259	946
SLC32A1	GPHN	Q9NQX3	940
SLC32A1	SLC17A6	Q9P2U8	898
SLC32A1	SLC17A8	Q8NDX2	827
SLC32A1	DLG4	P78352	817
SLC32A1	SYN1	P17600	816
SLC32A1	SLC18A3	Q16572	793
SLC32A1	PVALB	P20472	776
SLC32A1	SYN2	Q92777	750
SLC32A1	SYN3	O14994	749
SLC32A1	SLC38A3	Q99624	749
SLC32A1	SLC6A1	P30531	742
SLC32A1	SLC6A5	Q9Y345	739

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SLC32A1	NPLOC4	psi-mi:“MI:0914”(association)	0.530
DNAJC5	SLC32A1	psi-mi:“MI:0915”(physical association)	0.400
SLC32A1	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
SLC32A1	CST1	psi-mi:“MI:0914”(association)	0.350
AXDND1	SRP72	psi-mi:“MI:0914”(association)	0.350
SLC32A1	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (117): RNF181 (Affinity Capture-MS), CST1 (Affinity Capture-MS), DNAJC5 (FRET), SLC32A1 (Affinity Capture-Luminescence), SLC32A1 (Co-localization), SLC32A1 (Two-hybrid), SLC32A1 (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), RNF181 (Affinity Capture-MS), SLC32A1 (Affinity Capture-MS), SLC32A1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), AIMP1 (Affinity Capture-MS), APEX1 (Affinity Capture-MS), BASP1 (Affinity Capture-MS)

ESM2 similar proteins: A1L272, A6QL92, B8AF63, E2RFJ3, E7EXX2, O35458, O35633, O54902, O80605, P49281, P49282, P51027, P57057, P58355, Q0VA82, Q28CV2, Q569T7, Q5F383, Q5R6J3, Q5RD30, Q5U3U7, Q62052, Q640L2, Q6DEJ6, Q6DIV6, Q6GPQ3, Q6GQE1, Q6P499, Q6PF45, Q6YK44, Q7RTT9, Q8BGN5, Q8BH31, Q8CBH5, Q8MIQ9, Q8NA29, Q8NBI5, Q8NHS3, Q8R070, Q8R139

Diamond homologs: O35458, O35633, P34579, Q6DIV6, Q6PF45, Q95KE2, Q9H598

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

95 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	83
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3064670	NM_080552.3(SLC32A1):c.806T>A (p.Leu269Gln)	Pathogenic
1329949	NM_080552.3(SLC32A1):c.806T>C (p.Leu269Pro)	Likely pathogenic
1329950	NM_080552.3(SLC32A1):c.965T>G (p.Phe322Cys)	Likely pathogenic
3365638	NM_080552.3(SLC32A1):c.272C>G (p.Ala91Gly)	Likely pathogenic

SpliceAI

165 predictions. Top by Δscore:

Variant	Effect	Δscore
20:38725115:G:GA	donor_loss	1.0000
20:38725116:T:A	donor_loss	1.0000
20:38725115:G:GG	donor_gain	0.9900
20:38727451:GGGC:G	acceptor_gain	0.9900
20:38727446:CCACA:C	acceptor_loss	0.9800
20:38727447:CACA:C	acceptor_loss	0.9800
20:38727449:CA:C	acceptor_loss	0.9800
20:38727450:AG:A	acceptor_gain	0.9800
20:38727451:G:GT	acceptor_loss	0.9800
20:38727451:GG:G	acceptor_gain	0.9800
20:38725113:AG:A	donor_gain	0.9600
20:38725114:GG:G	donor_gain	0.9600
20:38727448:ACAG:A	acceptor_gain	0.9600
20:38727442:C:A	acceptor_gain	0.9500
20:38725110:TCCAG:T	donor_gain	0.9400
20:38727450:A:AG	acceptor_gain	0.9400
20:38727451:G:GG	acceptor_gain	0.9400
20:38727442:C:CA	acceptor_loss	0.9300
20:38725112:CAG:C	donor_gain	0.9200
20:38726007:GC:G	donor_gain	0.9100
20:38727451:GGGCA:G	acceptor_gain	0.9100
20:38725392:G:GT	donor_gain	0.9000
20:38727450:AGG:A	acceptor_gain	0.9000
20:38727451:GGG:G	acceptor_gain	0.9000
20:38725111:CCAG:C	donor_gain	0.8600
20:38725029:TGGG:T	donor_gain	0.8500
20:38725387:TG:T	donor_gain	0.8500
20:38725393:A:T	donor_gain	0.8500
20:38728634:GAC:G	donor_gain	0.7700
20:38727545:ACC:A	acceptor_gain	0.7300

AlphaMissense

3433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:38725085:G:C	A121P	1.000
20:38725089:G:A	G122D	1.000
20:38725091:T:A	W123R	1.000
20:38725091:T:C	W123R	1.000
20:38725105:C:A	N127K	1.000
20:38725105:C:G	N127K	1.000
20:38727452:G:C	G131R	1.000
20:38727452:G:T	G131C	1.000
20:38727458:T:C	F133L	1.000
20:38727460:C:A	F133L	1.000
20:38727460:C:G	F133L	1.000
20:38727467:G:C	G136R	1.000
20:38727474:C:A	P138H	1.000
20:38727474:C:T	P138L	1.000
20:38727546:C:T	T162I	1.000
20:38727548:G:C	G163R	1.000
20:38727558:T:C	L166P	1.000
20:38727567:G:A	C169Y	1.000
20:38727568:C:G	C169W	1.000
20:38727570:T:C	L170P	1.000
20:38727702:T:C	L214P	1.000
20:38727713:T:C	C218R	1.000
20:38727714:G:A	C218Y	1.000
20:38727715:C:G	C218W	1.000
20:38727720:T:C	L220P	1.000
20:38727734:A:C	S225R	1.000
20:38727736:T:A	S225R	1.000
20:38727736:T:G	S225R	1.000
20:38727744:T:C	L228P	1.000
20:38727788:T:A	W243R	1.000

dbSNP variants (sampled 300 via entrez): RS1000849821 (20:38724122 A>G), RS1000923399 (20:38723814 C>G), RS1001007774 (20:38724383 TG>T), RS1001097482 (20:38724102 A>G), RS1001149766 (20:38723908 C>G), RS1002040402 (20:38723491 C>A,G), RS1002198803 (20:38723204 C>T), RS1002381827 (20:38729597 C>A,G,T), RS1003111540 (20:38726495 T>A), RS1003127033 (20:38727963 T>A), RS1003447285 (20:38727911 T>A,C), RS1004750306 (20:38729332 G>T), RS1004811754 (20:38724644 G>GC), RS1004906392 (20:38724418 A>C,G), RS1005342626 (20:38727391 G>A,T)

Disease associations

OMIM: gene MIM:616440 | disease phenotypes: MIM:620755, MIM:620774, MIM:604233

GenCC curated gene-disease

Disease	Classification	Inheritance
generalized epilepsy with febrile seizures plus, type 12	Strong	Autosomal dominant
developmental and epileptic encephalopathy 114	Strong	Autosomal dominant

Mondo (6): intellectual disability (MONDO:0001071), generalized epilepsy with febrile seizures plus, type 12 (MONDO:0958324), developmental and epileptic encephalopathy 114 (MONDO:0958331), obesity disorder (MONDO:0011122), developmental and epileptic encephalopathy (MONDO:0100620), generalized epilepsy with febrile seizures plus (MONDO:0018214)

Orphanet (4): Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Genetic epilepsy with febrile seizure plus (Orphanet:36387), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

112 total (30 of 112 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000577	Exotropia
HP:0000664	Synophrys
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000826	Precocious puberty
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002539_92	Schizophrenia	1.000000e-11
GCST003367_4	circulating leptin levels	7.000000e-07
GCST003368_4	circulating leptin levels adjusted for BMI	2.000000e-07
GCST003368_9	circulating leptin levels adjusted for BMI	8.000000e-06
GCST006803_7	Schizophrenia	8.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005000	leptin measurement
EFO:0007793	BMI-adjusted leptin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C565808	Generalized Epilepsy with Febrile Seizures Plus (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC32 vesicular inhibitory amino acid transporter

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
vigabatrin	Inhibition	2.1	pIC50

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Tretinoin	decreases expression, increases expression	2
trichostatin A	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Lead	affects expression	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1

Clinical trials (associated diseases)

197 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders