SLMAP

Summary

SLMAP (sarcolemma associated protein, HGNC:16643) is a protein-coding gene on chromosome 3p14.3, encoding Sarcolemmal membrane-associated protein (Q14BN4). Associates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex. It is a selective cancer dependency (DepMap: 15.9% of cell lines).

This gene encodes a component of a conserved striatin-interacting phosphatase and kinase complex. Striatin family complexes participate in a variety of cellular processes including signaling, cell cycle control, cell migration, Golgi assembly, and apoptosis. The protein encoded by this gene is a coiled-coil, tail-anchored membrane protein with a single C-terminal transmembrane domain that is posttranslationally inserted into membranes. Mutations in this gene are associated with Brugada syndrome, a cardiac channelopathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7871 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brugada syndrome (Supportive, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 715 total
• Phenotypes (HPO): 12
• Cancer dependency (DepMap): dependent in 15.9% of screened cell lines
• MANE Select transcript: NM_001377540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16643
Approved symbol	SLMAP
Name	sarcolemma associated protein
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Aliases	SLAP, KIAA1601
Ensembl gene	ENSG00000163681
Ensembl biotype	protein_coding
OMIM	602701
Entrez	7871

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 42 protein_coding, 7 retained_intron, 7 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000295951, ENST00000295952, ENST00000383718, ENST00000416658, ENST00000417128, ENST00000428312, ENST00000438794, ENST00000449503, ENST00000459654, ENST00000460223, ENST00000461354, ENST00000465203, ENST00000466255, ENST00000467901, ENST00000472546, ENST00000475055, ENST00000476471, ENST00000481846, ENST00000494088, ENST00000497084, ENST00000655012, ENST00000657480, ENST00000658689, ENST00000659705, ENST00000659926, ENST00000662629, ENST00000664084, ENST00000667800, ENST00000670768, ENST00000671191, ENST00000705628, ENST00000705629, ENST00000705630, ENST00000705648, ENST00000705649, ENST00000705650, ENST00000705651, ENST00000705652, ENST00000705653, ENST00000705654, ENST00000865054, ENST00000865055, ENST00000865056, ENST00000865057, ENST00000936712, ENST00000936713, ENST00000936714, ENST00000936715, ENST00000957856, ENST00000957857, ENST00000957858, ENST00000957859, ENST00000957860, ENST00000957861, ENST00000957862, ENST00000957863, ENST00000957864, ENST00000957865

RefSeq mRNA: 26 — MANE Select: NM_001377540 NM_001304420, NM_001304421, NM_001304422, NM_001304423, NM_001311178, NM_001377538, NM_001377539, NM_001377540, NM_001377541, NM_001377542, NM_001377545, NM_001377549, NM_001377551, NM_001377552, NM_001377555, NM_001377557, NM_001377559, NM_001377562, NM_001377921, NM_001377922, NM_001377923, NM_001377924, NM_001377925, NM_001377926, NM_001377927, NM_007159

CCDS: CCDS33774, CCDS77757, CCDS77758, CCDS93295, CCDS93296, CCDS93297, CCDS93298, CCDS93299, CCDS93300, CCDS93301

Canonical transcript exons

ENST00000671191 — 25 exons

Exon	Start	End
ENSE00001077175	57916906	57917077
ENSE00001077188	57912381	57912701
ENSE00001518947	57756548	57757849
ENSE00001693887	57925845	57925934
ENSE00003458506	57864548	57864716
ENSE00003466734	57831383	57831530
ENSE00003469148	57896873	57896932
ENSE00003469998	57907884	57908006
ENSE00003473596	57849754	57849816
ENSE00003475186	57871636	57871698
ENSE00003502411	57841299	57841371
ENSE00003525198	57847197	57847233
ENSE00003594464	57864807	57864857
ENSE00003596953	57858088	57858159
ENSE00003597354	57860699	57860839
ENSE00003619002	57857733	57857828
ENSE00003625243	57890041	57890100
ENSE00003644487	57865242	57865292
ENSE00003644964	57913158	57913275
ENSE00003649879	57922889	57923023
ENSE00003665424	57861949	57862086
ENSE00003666794	57909076	57909150
ENSE00003784256	57896511	57896591
ENSE00003866719	57756309	57756342
ENSE00003871726	57927296	57930003

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1772 / max 648.9806, expressed in 1815 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36997	24.3372	1814
37005	2.4190	197
37004	0.6845	117
36999	0.2561	101
36998	0.1350	56
37008	0.1265	41
37002	0.1088	48
37007	0.0470	14
37006	0.0360	15
37003	0.0270	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.39	gold quality
cauda epididymis	UBERON:0004360	99.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.28	gold quality
left ventricle myocardium	UBERON:0006566	99.24	gold quality
myocardium	UBERON:0002349	99.09	gold quality
smooth muscle tissue	UBERON:0001135	98.99	gold quality
seminal vesicle	UBERON:0000998	98.75	gold quality
vena cava	UBERON:0004087	98.56	gold quality
heart right ventricle	UBERON:0002080	98.42	gold quality
popliteal artery	UBERON:0002250	98.23	gold quality
tibial artery	UBERON:0007610	98.22	gold quality
mucosa of stomach	UBERON:0001199	98.14	gold quality
artery	UBERON:0001637	97.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.97	gold quality
superficial temporal artery	UBERON:0001614	97.95	gold quality
urethra	UBERON:0000057	97.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.85	gold quality
lower esophagus	UBERON:0013473	97.83	gold quality
epithelial cell of pancreas	CL:0000083	97.72	gold quality
deltoid	UBERON:0001476	97.66	gold quality
aorta	UBERON:0000947	97.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.55	gold quality
myometrium	UBERON:0001296	97.34	gold quality
upper arm skin	UBERON:0004263	97.31	gold quality
left uterine tube	UBERON:0001303	97.25	gold quality
urinary bladder	UBERON:0001255	97.10	gold quality
cardiac atrium	UBERON:0002081	97.01	gold quality
body of uterus	UBERON:0009853	96.99	gold quality
right atrium auricular region	UBERON:0006631	96.87	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	61.12
E-HCAD-11	yes	8.06
E-ANND-3	yes	6.88
E-CURD-112	no	2.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

147 targeting SLMAP, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AQ-5P	99.94	71.34	3426
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
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel. (PMID:23064965)
• The data suggests the potential role of SLMAP single nucleotide polymorphism as a risk factor for the susceptibility of diabetic retinopathy among type 2 diabetes patients in the Qatari population. (PMID:25880194)
• Here, the authors discover SAV1-mediated inhibition of the PP2A complex STRIPAK(SLMAP) as a key mechanism of MST1/2 activation. (PMID:29063833)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slmapa	ENSDARG00000054458
mus_musculus	Slmap	ENSMUSG00000021870
rattus_norvegicus	Slmap	ENSRNOG00000011307

Paralogs (2): TRAF3IP3 (ENSG00000009790), CCDC136 (ENSG00000128596)

Protein

Protein identifiers

Sarcolemmal membrane-associated protein — Q14BN4 (reviewed: Q14BN4)

All UniProt accessions (26): A0A590UJ16, A0A590UJ91, A0A590UJG7, A0A590UJH8, Q14BN4, A0A590UJK3, A0A590UJP6, A0A590UJS6, A0A590UJT5, A0A590UJU9, A0A590UK66, A0A5F9VB99, A0A994J4X6, A0A994J4X9, A0A994J558, A0A994J562, A0A994J5K5, A0A994J5K8, A0A994J7G6, A0A994J7U9, A0A994J7V1, H7BZK0, H7BZW9, H7C3M8, H7C5G9, H7C5S2

UniProt curated annotations — full annotation on UniProt →

Function. Associates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex. The (SIKE1:SLMAP)STRIPAK complex dephosphorylates STK3 leading to the inhibition of Hippo signaling and the control of cell growth. May play a role during myoblast fusion.

Subunit / interactions. Homodimer. Interacts with myosin. Interacts with SIKE1 and both associate with the STRIPAK core complex composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26. Interacts (via FHA domain) with STK3 (when phosphorylated); the interaction associates STK3 with the STRIPAK complex.

Subcellular location. Cell membrane. Sarcolemma. Cytoplasm. Myofibril. Sarcomere. M line. Z line. Cytoskeleton. Microtubule organizing center. Centrosome Endoplasmic reticulum membrane. Mitochondrion membrane Endoplasmic reticulum membrane.

Domain organisation. Alternative spliced transmembrane domains determine subcellular targeting. Isoforms 1, 2, 3 and 4 are targeted to endoplasmic reticulum membrane as well as mitochondrion membrane. Isoform 5 is not targeted to mitochondrion membrane but to endoplasmic reticulum membrane.

Miscellaneous. Incomplete sequence.

Similarity. Belongs to the SLMAP family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q14BN4-1	1	yes
Q14BN4-2	2
Q14BN4-3	3
Q14BN4-4	4
Q14BN4-5	5
Q14BN4-6	6
Q14BN4-7	7
Q14BN4-8	8

RefSeq proteins (26): NP_001291349, NP_001291350, NP_001291351, NP_001291352, NP_001298107, NP_001364467, NP_001364468, NP_001364469, NP_001364470, NP_001364471, NP_001364474, NP_001364478, NP_001364480, NP_001364481, NP_001364484, NP_001364486, NP_001364488, NP_001364491, NP_001364850, NP_001364851, NP_001364852, NP_001364853, NP_001364854, NP_001364855, NP_001364856, NP_009090 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR051176	Cent_Immune-Sig_Mod	Family

Pfam: PF00498

UniProt features (57 total): splice variant 15, strand 13, mutagenesis site 8, modified residue 3, sequence conflict 3, coiled-coil region 3, topological domain 2, transmembrane region 2, region of interest 2, helix 2, chain 1, compositionally biased region 1, domain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6AR0	X-RAY DIFFRACTION	1.08
6AR2	X-RAY DIFFRACTION	1.55
6AKM	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14BN4-F1	77.74	0.42

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 (3): 148, 448, 452

Mutagenesis-validated functional residues (8):

Position	Phenotype
182	loss of interaction with sike1.
186	loss of interaction with sike1.
189	loss of interaction with sike1.
193	loss of interaction with sike1.
799	no effect on location to mitochondrion membrane; when associated with l-825.
808–815	loss of mitochondrion membrane location.
808–809	loss of mitochondrion membrane location.
825	no effect on location to mitochondrion membrane; when associated with k-799.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 249 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_255, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, MODULE_317, GOBP_HIPPO_SIGNALING, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION, CHANDRAN_METASTASIS_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_MONOATOMIC_CATION_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (6): muscle contraction (GO:0006936), negative regulation of hippo signaling (GO:0035331), protein localization to plasma membrane (GO:0072659), regulation of membrane depolarization during cardiac muscle cell action potential (GO:1900825), regulation of sodium ion transmembrane transport (GO:1902305), hippo signaling (GO:0035329)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), smooth endoplasmic reticulum (GO:0005790), centrosome (GO:0005813), plasma membrane (GO:0005886), Z disc (GO:0030018), M band (GO:0031430), mitochondrial membrane (GO:0031966), sarcolemma (GO:0042383), FAR/SIN/STRIPAK complex (GO:0090443), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytoskeleton (GO:0005856), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
organelle membrane	2
cytoplasm	2
intracellular membrane-bounded organelle	2
muscle system process	1
hippo signaling	1
regulation of hippo signaling	1
negative regulation of intracellular signal transduction	1
protein localization to membrane	1
protein localization to cell periphery	1
membrane depolarization during cardiac muscle cell action potential	1
regulation of membrane depolarization during action potential	1
regulation of sodium ion transport	1
sodium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
intracellular signal transduction	1
protein binding	1
molecular adaptor activity	1
binding	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum	1
centriole	1
microtubule organizing center	1
membrane	1
cell periphery	1
I band	1
A band	1
mitochondrion	1
mitochondrial envelope	1
plasma membrane	1
protein-containing complex	1
endomembrane system	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1735 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLMAP	SIKE1	Q9BRV8	979
SLMAP	MOB4	Q9Y3A3	915
SLMAP	SLA	Q13239	896
SLMAP	STRIP1	Q5VSL9	870
SLMAP	STRN	O43815	866
SLMAP	FGFR1OP2	Q9NVK5	842
SLMAP	PPP2CA	P05323	815
SLMAP	STRIP2	Q9ULQ0	801
SLMAP	SLA2	Q9H6Q3	777
SLMAP	CTTNBP2	Q8WZ74	766
SLMAP	STRN3	Q13033	761
SLMAP	RANGRF	Q9HD47	730
SLMAP	PLEC	Q15149	721
SLMAP	CTTNBP2NL	Q9P2B4	718
SLMAP	PDCD10	Q9BUL8	708

IntAct

157 interactions, top by confidence:

A	B	Type	Score
PDCD10	STK25	psi-mi:“MI:0914”(association)	0.980
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
STK24	STK25	psi-mi:“MI:0914”(association)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
STRN3	STK25	psi-mi:“MI:0914”(association)	0.880
STRN3	STRN	psi-mi:“MI:0914”(association)	0.880
STRN3	STRN	psi-mi:“MI:2364”(proximity)	0.880
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
STRIP1	PPP2CB	psi-mi:“MI:0914”(association)	0.870
STK26	STRN	psi-mi:“MI:0914”(association)	0.860
PRDM14	CBFA2T2	psi-mi:“MI:0914”(association)	0.860
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
STRIP1	STK25	psi-mi:“MI:0914”(association)	0.840
MOB4	STRN	psi-mi:“MI:0914”(association)	0.790
PRPF19	AQR	psi-mi:“MI:0914”(association)	0.790
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
STK26	STK25	psi-mi:“MI:0914”(association)	0.790
SLMAP	STK4	psi-mi:“MI:0915”(physical association)	0.790
STK4	SLMAP	psi-mi:“MI:0403”(colocalization)	0.790

BioGRID (252): SLMAP (Two-hybrid), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), SLMAP (Affinity Capture-MS), PPP2R1B (Affinity Capture-MS), FGFR1OP2 (Affinity Capture-MS), STK26 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), MOB4 (Affinity Capture-MS), RABEP1 (Affinity Capture-MS)

ESM2 similar proteins: A0PJP4, A0PJT0, A2VDP1, A4IFK7, D3ZUQ0, E9PSL7, O14578, O75665, P0C219, P49025, P97817, Q01850, Q0IHE5, Q14BN4, Q17QG3, Q28623, Q3LGD4, Q3SYW5, Q3URD3, Q3V079, Q4R3X1, Q4R7Y8, Q58A65, Q5DTM8, Q5EBL4, Q5R5R4, Q5VTR2, Q5ZJA3, Q5ZLS3, Q62172, Q62796, Q68CZ1, Q6AYA0, Q6DFC2, Q6DH86, Q6NRH3, Q6ZUS6, Q7Z3E2, Q86VS8, Q8BR07

Diamond homologs: A6ZRW7, O23305, O74388, P0C219, P38823, P53924, Q03944, Q06001, Q10322, Q14BN4, Q28623, Q2HJ46, Q3URD3, Q8VC56, P46017, Q80U49, Q9Y4F5, Q8C0G2, Q9Y228, A0QNG6, Q3TVA9, Q96JN2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF activation	5	18.9×	2e-03
Degradation of beta-catenin by the destruction complex	5	9.7×	7e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	6	7.9×	7e-03
COPI-mediated anterograde transport	6	7.4×	7e-03
Mitotic Prometaphase	7	5.4×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of hippo signaling	6	34.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	357
Likely benign	279
Benign	38

Top pathogenic / likely-pathogenic (0)

SpliceAI

4480 predictions. Top by Δscore:

Variant	Effect	Δscore
3:57831378:TGCAG:T	acceptor_loss	1.0000
3:57831379:GCAGT:G	acceptor_loss	1.0000
3:57831381:A:AG	acceptor_gain	1.0000
3:57831382:G:GT	acceptor_gain	1.0000
3:57831382:GT:G	acceptor_gain	1.0000
3:57831382:GTT:G	acceptor_gain	1.0000
3:57831382:GTTT:G	acceptor_gain	1.0000
3:57831382:GTTTT:G	acceptor_gain	1.0000
3:57831527:AAAG:A	donor_loss	1.0000
3:57831528:AAGG:A	donor_loss	1.0000
3:57831529:AGGTA:A	donor_loss	1.0000
3:57831531:GT:G	donor_loss	1.0000
3:57831532:T:A	donor_loss	1.0000
3:57841372:G:GG	donor_gain	1.0000
3:57847195:A:AG	acceptor_gain	1.0000
3:57847196:G:GG	acceptor_gain	1.0000
3:57847234:G:GG	donor_gain	1.0000
3:57849748:TTCTA:T	acceptor_loss	1.0000
3:57849749:TCTA:T	acceptor_loss	1.0000
3:57849750:CTAGG:C	acceptor_loss	1.0000
3:57849751:TA:T	acceptor_loss	1.0000
3:57849753:G:GT	acceptor_loss	1.0000
3:57857725:A:AG	acceptor_gain	1.0000
3:57857822:TTGGC:T	donor_gain	1.0000
3:57860695:GTAG:G	acceptor_loss	1.0000
3:57860697:A:AG	acceptor_gain	1.0000
3:57860697:A:G	acceptor_loss	1.0000
3:57860698:G:GG	acceptor_gain	1.0000
3:57860698:GA:G	acceptor_gain	1.0000
3:57860698:GAAT:G	acceptor_gain	1.0000

AlphaMissense

5569 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:57757668:C:A	A6D	1.000
3:57757709:C:A	R20S	1.000
3:57757716:T:A	V22D	1.000
3:57757740:T:A	I30N	1.000
3:57757742:G:C	G31R	1.000
3:57757742:G:T	G31C	1.000
3:57757743:G:A	G31D	1.000
3:57757743:G:T	G31V	1.000
3:57757745:C:A	R32S	1.000
3:57757745:C:G	R32G	1.000
3:57757745:C:T	R32C	1.000
3:57757746:G:C	R32P	1.000
3:57757755:C:A	A35D	1.000
3:57757782:C:A	A44D	1.000
3:57757787:T:C	F46L	1.000
3:57757788:T:C	F46S	1.000
3:57757789:T:A	F46L	1.000
3:57757789:T:G	F46L	1.000
3:57757793:T:C	C48R	1.000
3:57757794:G:A	C48Y	1.000
3:57757794:G:T	C48F	1.000
3:57757795:C:G	C48W	1.000
3:57757796:A:G	K49E	1.000
3:57757797:A:T	K49I	1.000
3:57757798:A:C	K49N	1.000
3:57757798:A:T	K49N	1.000
3:57757799:G:A	V50M	1.000
3:57757800:T:A	V50E	1.000
3:57757803:T:A	L51Q	1.000
3:57757803:T:C	L51P	1.000

dbSNP variants (sampled 300 via entrez): RS1000022901 (3:57783629 G>T), RS1000028811 (3:57833805 T>C), RS1000054794 (3:57884589 C>G), RS1000059467 (3:57923489 A>G,T), RS1000077575 (3:57790303 A>C), RS1000102258 (3:57834665 C>T), RS1000116127 (3:57864305 G>A,T), RS1000184629 (3:57846666 T>A), RS1000192170 (3:57820710 G>A), RS1000193184 (3:57777481 G>A), RS1000199569 (3:57808744 G>C,T), RS1000216402 (3:57897573 G>A), RS1000227790 (3:57770698 C>T), RS1000302476 (3:57796461 C>T), RS1000309820 (3:57814618 G>A)

Disease associations

OMIM: gene MIM:602701 | disease phenotypes: MIM:601144

GenCC curated gene-disease

Disease	Classification	Inheritance
Brugada syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Brugada syndrome	Refuted	AD
Brugada syndrome	Disputed	AD

Mondo (3): Brugada syndrome (MONDO:0015263), long QT syndrome (MONDO:0002442), cardiac arrest (MONDO:0000745)

Orphanet (1): Brugada syndrome (Orphanet:130)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0001279	Syncope
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:0012251	ST segment elevation

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001762_474	Obesity-related traits	5.000000e-06
GCST003815_45	Late-onset Alzheimer’s disease	2.000000e-06
GCST007094_173	Diastolic blood pressure	2.000000e-09
GCST007268_13	Diastolic blood pressure	3.000000e-08
GCST007429_108	Lung function (FVC)	1.000000e-11
GCST007430_96	Peak expiratory flow	3.000000e-10
GCST007431_85	Lung function (FEV1/FVC)	2.000000e-19
GCST007432_122	FEV1	4.000000e-26
GCST007692_102	Chronic obstructive pulmonary disease	2.000000e-08
GCST008664_15	Lung function (low FEV1 vs high FEV1)	3.000000e-08
GCST90002398_122	Neutrophil count	1.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:1001870	late-onset Alzheimers disease
EFO:0006336	diastolic blood pressure
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0004833	neutrophil count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D006323	Heart Arrest	C14.280.383
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
1-nitropyrene	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Vehicle Emissions	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Theophylline	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

299 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
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00101881	PHASE4	COMPLETED	Transthoracic Incremental Monophasic Versus Biphasic by Emergency Responders (TIMBER)
NCT00127907	PHASE4	COMPLETED	Vasopressin and Epinephrine Versus Epinephrine Alone in Cardiac Arrest
NCT00180362	PHASE4	COMPLETED	Quick ICD Study: Is Extensive Electrophysiological Testing Before, During and After ICD-Implantation Still Necessary ?
NCT00392639	PHASE4	COMPLETED	Clinical and Economical Interest of Endovascular Cooling in the Management of Cardiac Arrest (ICEREA Study)
NCT00644722	PHASE4	COMPLETED	Out-of-Hospital Intubation With Metal Single Use Laryngoscope Blades
NCT00827957	PHASE4	COMPLETED	Comparing Therapeutic Hypothermia Using External and Internal Cooling for Post-Cardiac Arrest Patients
NCT00843297	PHASE4	COMPLETED	COOL-Trial: Outcome With Invasive and Non-invasive Cooling After Cardiac Arrest
NCT01009606	PHASE4	COMPLETED	Cardiopulmonary Resuscitation Witnessing by a Relative
NCT01083784	PHASE4	UNKNOWN	The Benefit of Prophylactic Anticonvulsant in Post Cardiac Arrest Syndrome With Induced Mild Hypothermia
NCT01155622	PHASE4	COMPLETED	Trial of Different Hypothermia Temperatures in Patients Recovered From Out-of-hospital Cardiac Arrest
NCT01374061	PHASE4	WITHDRAWN	Pre Hospital Evaluation of Video Laryngoscopy
NCT02088736	PHASE4	COMPLETED	Intraosseous vs Intravenous Access for Cardiac Arrest Treatment
NCT02224274	PHASE4	COMPLETED	Antiplatelet Therapy After Cardiac Arrest
NCT02367755	PHASE4	UNKNOWN	Therapeutic Hypothermia With Propofol in Survival and Neurological Prognoses After Cardiac Arrest
NCT03317197	PHASE4	UNKNOWN	Effect of Vasopressin, Steroid, and Epinephrine Treatment in Patients With Out-of-hospital Cardiac Arrest
NCT04287842	PHASE4	WITHDRAWN	Impact if Desflurane Preconditioning on the Content of the Phospho-GSK-3b in the Rat’s Neurons in the Model of I/R
NCT05173740	PHASE4	RECRUITING	Rehabilitation for Survivors of Out-of-hospital Cardiac Arrest
NCT05205031	PHASE4	ACTIVE_NOT_RECRUITING	Intravenous Vs. Intraosseous Vascular Access During Out-of-Hospital
NCT05564130	PHASE4	ACTIVE_NOT_RECRUITING	Bicarbonate for In-Hospital Cardiac Arrest
NCT05956431	PHASE4	UNKNOWN	RCT Study of Levosimendan Improving Prognosis of Cardiac Arrest
NCT06081283	PHASE4	TERMINATED	Antiseizure Medication in Seizure Networks at Early Acute Brain Injury
NCT06156059	PHASE4	UNKNOWN	Oral Bedtime Melatonin in Critically Ill Patients
NCT06353334	PHASE4	RECRUITING	Butylphthalide’s Safety and Efficacy for Improving Neurological Function Prognosis in Patients With Cardiac Arrest (BNCA Trial)
NCT06530641	PHASE4	RECRUITING	Evaluation of Clinical Impact of the Type of Cardioplegia Used in the Patient Undergoing Major Cardiac Surgery.
NCT06572085	PHASE4	RECRUITING	Neuroprotective Effect of Butylphthalide for Cardiac Arrest Patients
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000502	PHASE3	COMPLETED	Evaluation of SC-V Versus Conventional CPR
NCT00000525	PHASE3	COMPLETED	Diuretics, Hypertension, and Arrhythmias Clinical Trial
NCT00000526	PHASE3	COMPLETED	Cardiac Arrhythmia Suppression Trial (CAST)
NCT00004560	PHASE3	COMPLETED	Public Access Defibrillation (PAD) Community Trial
NCT00120965	PHASE3	TERMINATED	AutoPulse Assisted Prehospital International Resuscitation Trial (ASPIRE)
NCT00139542	PHASE3	COMPLETED	AED Use in Out-of-Hospital Cardiac Arrest: A New Algorithm Named One Shock Per Minute
NCT00157261	PHASE3	TERMINATED	Thrombolysis Using Tenecteplase (Metalyse®) in Cardiac Arrest - The TROICA Trial