GPD1L

Summary

GPD1L (glycerol-3-phosphate dehydrogenase 1 like, HGNC:28956) is a protein-coding gene on chromosome 3p22.3, encoding Glycerol-3-phosphate dehydrogenase 1-like protein (Q8N335). Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also….

The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS).

Source: NCBI Gene 23171 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brugada syndrome 2 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 464 total
• Phenotypes (HPO): 15
• MANE Select transcript: NM_015141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28956
Approved symbol	GPD1L
Name	glycerol-3-phosphate dehydrogenase 1 like
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0089
Ensembl gene	ENSG00000152642
Ensembl biotype	protein_coding
OMIM	611778
Entrez	23171

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000282541, ENST00000425459, ENST00000428684, ENST00000429432, ENST00000431009, ENST00000474846, ENST00000496151, ENST00000902848, ENST00000902849, ENST00000902850, ENST00000951741, ENST00000951742, ENST00000951743

RefSeq mRNA: 1 — MANE Select: NM_015141 NM_015141

CCDS: CCDS33729

Canonical transcript exons

ENST00000282541 — 8 exons

Exon	Start	End
ENSE00001134607	32165814	32168709
ENSE00001134616	32106620	32106758
ENSE00003480545	32158876	32159109
ENSE00003567638	32138587	32138727
ENSE00003572257	32159568	32159674
ENSE00003598626	32128076	32128253
ENSE00003674717	32146622	32146734
ENSE00003691527	32140228	32140366

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2650 / max 178.0471, expressed in 1617 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35871	8.7780	1535
35868	0.7346	292
35869	0.6377	276
35870	0.1147	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	98.80	gold quality
heart right ventricle	UBERON:0002080	98.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.47	gold quality
left ventricle myocardium	UBERON:0006566	98.41	gold quality
triceps brachii	UBERON:0001509	98.39	gold quality
deltoid	UBERON:0001476	98.31	gold quality
myocardium	UBERON:0002349	98.26	gold quality
diaphragm	UBERON:0001103	98.21	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.08	gold quality
gluteal muscle	UBERON:0002000	97.98	gold quality
body of tongue	UBERON:0011876	97.88	gold quality
skeletal muscle tissue	UBERON:0001134	97.85	gold quality
quadriceps femoris	UBERON:0001377	97.81	gold quality
vastus lateralis	UBERON:0001379	97.81	gold quality
tibialis anterior	UBERON:0001385	97.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.33	gold quality
parotid gland	UBERON:0001831	97.21	gold quality
muscle organ	UBERON:0001630	97.16	gold quality
skeletal muscle organ	UBERON:0014892	97.16	gold quality
gastrocnemius	UBERON:0001388	97.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.09	gold quality
muscle tissue	UBERON:0002385	97.05	gold quality
muscle of leg	UBERON:0001383	96.87	gold quality
vena cava	UBERON:0004087	96.87	gold quality
esophagus squamous epithelium	UBERON:0006920	96.85	gold quality
cardiac atrium	UBERON:0002081	96.70	gold quality
cardiac ventricle	UBERON:0002082	96.69	gold quality
heart left ventricle	UBERON:0002084	96.64	gold quality
right atrium auricular region	UBERON:0006631	96.56	gold quality
middle temporal gyrus	UBERON:0002771	96.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	261.10
E-CURD-119	yes	17.02
E-ANND-3	yes	14.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting GPD1L, 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-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 18)

• mutations in GPD1-L as a pathogenic cause for a small subset of sudden infant death syndrome via a secondary loss-of-function mechanism (PMID:17967976)
• A GPD1-L mutation decreases SCN5A surface membrane expression, reduces inward Na+ current, and causes Brugada syndrome (PMID:17967977)
• No non-synonymous mutations were found, indicating that GPD1L does not appear to be a major cause of Brugada syndrome in a Japanese population. (PMID:18762705)
• GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A. (PMID:19666841)
• Mutations of GPD1-L may downregulate Na(v)1.5 by altering the oxidized to reduced NAD(H) balance. (PMID:19745168)
• hypoxia-induced miR-210 represses GPD1L, contributing to suppression of prolyl hydroxylases activity, and increases of HIF-1alpha protein levels. (PMID:21555452)
• Common variations in or near CASQ2, GPD1L, and NOS1AP are associated with increased risk of sudden cardiac death in patients with coronary artery disease (PMID:21685173)
• The results of real-time PCR showed that, compared with the paired normal tissues, mRNA levels of GPD1L were decreased significantly in head and neck squamous cell carcinoma. (PMID:24274692)
• In a nonreferred nationwide Danish cohort of SIDS cases, up to 5/66 (7.5%) of SIDS cases can be explained by genetic variants in the sodium channel complex genes. (PMID:25757662)
• Then bioinformatic analysis identified potential target sites of the miR-181a located in the 3’ untranslated region of GPD1L. Increased GPD1L and decreased miRNA-181a were observed in tissues from osteoarthritis patients. Our results demonstrated that miR-181a may play an important role in the pathogenesis of Osteoarthritis through targeting GPD1L and regulating chondrocyte apoptosis. (PMID:28280258)
• The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. (PMID:28496128)
• This study not only further supported the important role of GPD1L in Cardiac conduction disease, but also expanded the spectrum of GPD1L mutations (PMID:29077258)
• Findings indicate that downregulation of NEAT1 aggravated progression of OA via modulating the miR-181a/GPD1L axis, providing a novel insight into the mechanism of OA pathogenesis. (PMID:31658244)
• A novel mutation in GPD1L associated with early repolarization syndrome via modulation of cardiomyocyte fast sodium currents. (PMID:31922248)
• GPD1L is negatively associated with HIF1alpha expression and predicts lymph node metastasis in oral and HPV- Oropharyngeal cancer. (PMID:33107174)
• Atrial myocyte-derived exosomal microRNA contributes to atrial fibrosis in atrial fibrillation. (PMID:36064558)
• GPD1L inhibits renal cell carcinoma progression by regulating PINK1/Parkin-mediated mitophagy. (PMID:37382962)
• Prognostic and Predictive Utility of GPD1L in Human Hepatocellular Carcinoma. (PMID:37685919)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpd1l	ENSDARG00000040024
mus_musculus	Gpd1l	ENSMUSG00000050627
rattus_norvegicus	Gpd1l	ENSRNOG00000026455
drosophila_melanogaster	Gpdh1	FBGN0001128
drosophila_melanogaster	Gpdh2	FBGN0034825
drosophila_melanogaster	Gpdh3	FBGN0263048
caenorhabditis_elegans	gpdh-1	WBGENE00009824
caenorhabditis_elegans		WBGENE00010778

Paralogs (1): GPD1 (ENSG00000167588)

Protein

Protein identifiers

Glycerol-3-phosphate dehydrogenase 1-like protein — Q8N335 (reviewed: Q8N335)

All UniProt accessions (5): Q8N335, C9JFA7, C9JM46, C9K0P5, F8WC16

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also be reduced due to alterations of NAD(H) balance induced by DPD1L.

Subunit / interactions. Interacts with SCN5A.

Subcellular location. Cytoplasm.

Tissue specificity. Most highly expressed in heart tissue, with lower levels in the skeletal muscle, kidney, lung and other organs.

Disease relevance. Brugada syndrome 2 (BRGDA2) [MIM:611777] A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. The gene represented in this entry may be involved in disease pathogenesis.

Similarity. Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.

RefSeq proteins (1): NP_055956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006109	G3P_DH_NAD-dep_C	Domain
IPR006168	G3P_DH_NAD-dep	Family
IPR008927	6-PGluconate_DH-like_C_sf	Homologous_superfamily
IPR011128	G3P_DH_NAD-dep_N	Domain
IPR013328	6PGD_dom2	Homologous_superfamily
IPR017751	G3P_DH_NAD-dep_euk	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF01210, PF07479

Catalyzed reactions (Rhea), 1 shown:

• sn-glycerol 3-phosphate + NAD(+) = dihydroxyacetone phosphate + NADH + H(+) (RHEA:11092)

UniProt features (45 total): helix 18, strand 11, binding site 7, sequence variant 5, turn 2, chain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2PLA	X-RAY DIFFRACTION	2.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N335-F1	96.90	0.97

Functional residue map

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

Catalytic / active sites (1): 206 (proton acceptor)

Ligand- & substrate-binding residues (7): 12–17; 122; 155; 271–272; 271; 298; 300

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA

MSigDB gene sets: 302 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, BENPORATH_ES_WITH_H3K27ME3, TGCGCANK_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GGAMTNNNNNTCCY_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (11): regulation of heart rate (GO:0002027), carbohydrate metabolic process (GO:0005975), positive regulation of sodium ion transport (GO:0010765), NAD+ metabolic process (GO:0019674), glycerol-3-phosphate catabolic process (GO:0046168), regulation of ventricular cardiac muscle cell membrane depolarization (GO:0060373), ventricular cardiac muscle cell action potential (GO:0086005), positive regulation of protein localization to cell surface (GO:2000010), glycerol-3-phosphate metabolic process (GO:0006072), obsolete NADH oxidation (GO:0006116), obsolete NADH metabolic process (GO:0006734)

GO Molecular Function (8): oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), sodium channel regulator activity (GO:0017080), protein homodimerization activity (GO:0042803), transmembrane transporter binding (GO:0044325), NAD binding (GO:0051287), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), glycerol-3-phosphate dehydrogenase (NAD+) activity (GO:0141152)

GO Cellular Component (5): cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of heart contraction	1
regulation of biological quality	1
primary metabolic process	1
regulation of sodium ion transport	1
sodium ion transport	1
positive regulation of monoatomic ion transport	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
glycerol-3-phosphate metabolic process	1
organophosphate catabolic process	1
carbohydrate derivative catabolic process	1
regulation of membrane depolarization	1
cardiac muscle cell action potential involved in contraction	1
protein localization to cell surface	1
positive regulation of protein localization	1
regulation of protein localization to cell surface	1
alditol phosphate metabolic process	1
oxidoreductase activity, acting on CH-OH group of donors	1
sodium channel activity	1
ion channel regulator activity	1
identical protein binding	1
protein dimerization activity	1
protein binding	1
adenyl nucleotide binding	1
binding	1
catalytic activity	1
glycerol-3-phosphate dehydrogenase [NAD(P)+] activity	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPD1L	SCN5A	Q14524	965
GPD1L	KCNE3	Q9Y6H6	904
GPD1L	SCN3B	Q9NY72	901
GPD1L	SCN1B	Q07699	894
GPD1L	CACNB2	Q08289	868
GPD1L	HCN4	Q9Y3Q4	834
GPD1L	CACNA1C	Q13936	822
GPD1L	CAV3	P56539	817
GPD1L	KCNE2	Q9Y6J6	779
GPD1L	RANGRF	Q9HD47	773
GPD1L	KCNE4	Q8WWG9	723
GPD1L	SCN10A	Q9Y5Y9	716
GPD1L	KCNE5	Q9UJ90	692
GPD1L	KCNJ8	Q15842	686
GPD1L	SCN2B	O60939	676

IntAct

58 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
AIFM1	AK2	psi-mi:“MI:0914”(association)	0.570
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CCL5	C4A	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
	GPD1L	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
SCN5A	GPD1L	psi-mi:“MI:0915”(physical association)	0.400
SLAMF8	GPD1L	psi-mi:“MI:0915”(physical association)	0.400
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.350
BSG	METTL15	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
ISLR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
LAMP2	HSPA12A	psi-mi:“MI:0914”(association)	0.350
GPD1	IDH3B	psi-mi:“MI:0914”(association)	0.350
FAS	PEX1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CD80	POTEF	psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
KLRC4	RAP1BL	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): GPD1L (Affinity Capture-MS), GPD1L (Affinity Capture-MS), GPD1L (Affinity Capture-MS), GPD1L (Affinity Capture-MS), GPD1L (Affinity Capture-MS), GPD1L (Affinity Capture-MS), ALDOA (Co-fractionation), ALDOC (Co-fractionation), CYCS (Co-fractionation), GNPNAT1 (Co-fractionation), GPD1L (Co-fractionation), GPD1L (Co-fractionation), GPD1L (Co-fractionation), GPD1L (Co-fractionation), GPD1L (Co-fractionation)

ESM2 similar proteins: A2RVK7, A6QLJ3, O00442, O04226, O19069, O57656, O65361, P00341, P06801, P08507, P13086, P13697, P18562, P28227, P31754, P32296, P40927, P40939, P48163, P48605, P53596, P53597, Q01415, Q16798, Q29558, Q2HJ88, Q2KHX8, Q3ULJ0, Q4R3J0, Q58DR8, Q5R5V3, Q5R6J8, Q5R7P3, Q5XIZ6, Q6P824, Q801R8, Q8BMF3, Q8C3X4, Q8N335, Q8N442

Diamond homologs: A0A0F6AK91, A0KR80, A1RQ92, A2RCE5, A2RK98, A3DAM7, A4TSB8, A4Y1E6, A6WHD0, A7FCV2, A8AUM5, A9KUC1, A9R691, B0K3E2, B1JQV5, B2JYQ1, B3WCP6, B4U0Q8, B5XJM4, B8E3F7, B9DVX9, C0M6I2, L7IGD3, O35077, O57656, O67555, O97463, P07735, P08507, P0CT11, P0DB22, P0DB23, P13706, P13707, P21695, P21696, P34517, P41911, P52425, P61740

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	214
Likely benign	165
Benign	42

Top pathogenic / likely-pathogenic (0)

SpliceAI

1895 predictions. Top by Δscore:

Variant	Effect	Δscore
3:32106730:A:T	donor_gain	1.0000
3:32106799:G:GT	donor_gain	1.0000
3:32114641:C:A	acceptor_gain	1.0000
3:32128074:AGG:A	acceptor_gain	1.0000
3:32128075:GGG:G	acceptor_gain	1.0000
3:32128250:TGTGG:T	donor_loss	1.0000
3:32128252:TGGTA:T	donor_loss	1.0000
3:32128253:GGT:G	donor_loss	1.0000
3:32128254:G:T	donor_loss	1.0000
3:32128255:TAAGA:T	donor_loss	1.0000
3:32140364:TCGG:T	donor_loss	1.0000
3:32140366:GGT:G	donor_loss	1.0000
3:32140367:G:GG	donor_gain	1.0000
3:32140367:GTA:G	donor_loss	1.0000
3:32140368:T:TC	donor_loss	1.0000
3:32146617:A:AG	acceptor_gain	1.0000
3:32146618:A:G	acceptor_gain	1.0000
3:32146619:CAGG:C	acceptor_loss	1.0000
3:32146620:A:AG	acceptor_gain	1.0000
3:32146621:G:GA	acceptor_gain	1.0000
3:32146621:GGCA:G	acceptor_gain	1.0000
3:32146730:TTAAG:T	donor_loss	1.0000
3:32146731:TAAGG:T	donor_loss	1.0000
3:32146733:AG:A	donor_loss	1.0000
3:32146734:G:GC	donor_loss	1.0000
3:32146735:G:C	donor_loss	1.0000
3:32159106:G:GT	donor_gain	1.0000
3:32159106:G:T	donor_gain	1.0000
3:32159107:A:T	donor_gain	1.0000
3:32159564:TAA:T	acceptor_loss	1.0000

AlphaMissense

2318 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:32146734:G:C	K206N	1.000
3:32146734:G:T	K206N	1.000
3:32159031:C:G	C258W	1.000
3:32138727:G:C	K122N	0.999
3:32138727:G:T	K122N	0.999
3:32140228:G:C	G123R	0.999
3:32140312:G:A	G151R	0.999
3:32140312:G:C	G151R	0.999
3:32140313:G:A	G151E	0.999
3:32140320:C:A	N153K	0.999
3:32140320:C:G	N153K	0.999
3:32146732:A:G	K206E	0.999
3:32146733:A:C	K206T	0.999
3:32146733:A:T	K206M	0.999
3:32158878:C:A	N207K	0.999
3:32158878:C:G	N207K	0.999
3:32158964:A:T	E236V	0.999
3:32159026:A:C	S257R	0.999
3:32159028:C:A	S257R	0.999
3:32159028:C:G	S257R	0.999
3:32159030:G:A	C258Y	0.999
3:32159041:G:C	D262H	0.999
3:32159042:A:C	D262A	0.999
3:32159045:T:C	L263P	0.999
3:32106745:G:C	G12R	0.998
3:32106746:G:A	G12D	0.998
3:32128076:G:C	W16C	0.998
3:32128076:G:T	W16C	0.998
3:32128214:T:A	N62K	0.998
3:32128214:T:G	N62K	0.998

dbSNP variants (sampled 300 via entrez): RS1000017080 (3:32126347 G>C), RS1000178105 (3:32146271 A>G), RS1000205633 (3:32120898 G>A), RS1000227415 (3:32159999 A>G), RS1000231293 (3:32121171 C>G), RS1000348327 (3:32107575 C>T), RS1000368608 (3:32154002 A>C), RS1000378356 (3:32115067 A>G), RS1000428910 (3:32147870 A>G), RS1000442439 (3:32154283 G>A,T), RS1000460807 (3:32108872 C>T), RS1000491811 (3:32143920 T>G), RS1000603015 (3:32142563 T>G), RS1000603180 (3:32139224 T>A), RS1000635594 (3:32142905 A>C)

Disease associations

OMIM: gene MIM:611778 | disease phenotypes: MIM:601144, MIM:611777, MIM:181500, MIM:194200, MIM:192600

GenCC curated gene-disease

Disease	Classification	Inheritance
Brugada syndrome 2	Limited	Unknown
Brugada syndrome 1	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Brugada syndrome 1	Disputed	AD

Mondo (10): Brugada syndrome (MONDO:0015263), Brugada syndrome 2 (MONDO:0012728), schizophrenia (MONDO:0005090), cardiomyopathy (MONDO:0004994), dilated cardiomyopathy (MONDO:0005021), Wolff-Parkinson-White syndrome (MONDO:0008685), long QT syndrome (MONDO:0002442), hypertrophic cardiomyopathy (MONDO:0005045), familial hypertrophic cardiomyopathy (MONDO:0024573), Brugada syndrome 1 (MONDO:0011001)

Orphanet (8): Brugada syndrome (Orphanet:130), Rare cardiomyopathy (Orphanet:167848), Dilated cardiomyopathy (Orphanet:217604), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

15 total (19 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001279	Syncope
HP:0001645	Sudden cardiac death
HP:0001649	Tachycardia
HP:0001663	Ventricular fibrillation
HP:0001695	Cardiac arrest
HP:0004308	Ventricular arrhythmia
HP:0004751	Paroxysmal ventricular tachycardia
HP:0004755	Supraventricular tachycardia
HP:0011704	Sick sinus syndrome
HP:0011705	First degree atrioventricular block
HP:0011712	Complete right bundle branch block
HP:0011715	Trifascicular block
HP:0012248	Prolonged PR interval
HP:0012251	ST segment elevation
HP:0100753	Schizophrenia
HP:0001644	Dilated cardiomyopathy
HP:0001716	Wolff-Parkinson-White syndrome
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001281_2	Alcohol dependence	8.000000e-06
GCST002312_8	Periodontal disease-related phenotype (Socransky)	6.000000e-06
GCST004946_13	Schizophrenia	3.000000e-08

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C567087	Brugada Syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	8
trichostatin A	affects cotreatment, increases expression	3
Estradiol	increases expression, decreases expression, affects cotreatment	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	decreases expression, affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	increases expression	2
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
Am 580	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5QL	WAe009-A-80	Embryonic stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients