DLGAP5

Summary

DLGAP5 (DLG associated protein 5, HGNC:16864) is a protein-coding gene on chromosome 14q22.3, encoding Disks large-associated protein 5 (Q15398). Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells.

Predicted to enable microtubule binding activity. Predicted to be involved in several processes, including centrosome localization; kinetochore assembly; and mitotic spindle organization. Located in cytosol; nucleus; and spindle.

Source: NCBI Gene 9787 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brugada syndrome (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 325 total — 3 pathogenic
• MANE Select transcript: NM_014750

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16864
Approved symbol	DLGAP5
Name	DLG associated protein 5
Location	14q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0008, DLG1, HURP
Ensembl gene	ENSG00000126787
Ensembl biotype	protein_coding
OMIM	617859
Entrez	9787

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000247191, ENST00000395425, ENST00000554007, ENST00000554067, ENST00000557645, ENST00000940500, ENST00000940501, ENST00000940502, ENST00000940503, ENST00000940504

RefSeq mRNA: 2 — MANE Select: NM_014750 NM_001146015, NM_014750

CCDS: CCDS53897, CCDS9723

Canonical transcript exons

ENST00000247191 — 19 exons

Exon	Start	End
ENSE00000867238	55150799	55150848
ENSE00000867240	55152590	55152647
ENSE00000867241	55154617	55154806
ENSE00000867242	55158522	55158741
ENSE00000867243	55162971	55163075
ENSE00000867244	55169399	55169559
ENSE00000867245	55170702	55170787
ENSE00001093673	55181213	55181297
ENSE00001093676	55182370	55182432
ENSE00001093679	55183560	55183753
ENSE00001093684	55175346	55175472
ENSE00001093687	55175894	55176018
ENSE00001093693	55177062	55177336
ENSE00001093695	55179629	55179699
ENSE00001732707	55188942	55189180
ENSE00001744223	55191463	55191585
ENSE00001836421	55148135	55148473
ENSE00003664851	55151695	55151941
ENSE00003784578	55180656	55180778

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8877 / max 709.1135, expressed in 1321 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143366	17.9938	1316
143367	0.8939	550

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.65	gold quality
ventricular zone	UBERON:0003053	96.57	gold quality
oocyte	CL:0000023	92.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.54	gold quality
embryo	UBERON:0000922	92.46	gold quality
ganglionic eminence	UBERON:0004023	92.18	gold quality
trabecular bone tissue	UBERON:0002483	90.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.09	gold quality
bone marrow	UBERON:0002371	88.11	gold quality
bone marrow cell	CL:0002092	83.16	gold quality
sperm	CL:0000019	80.95	gold quality
endometrium epithelium	UBERON:0004811	80.35	gold quality
stromal cell of endometrium	CL:0002255	80.00	gold quality
testis	UBERON:0000473	79.08	gold quality
male germ cell	CL:0000015	78.84	gold quality
vermiform appendix	UBERON:0001154	78.62	gold quality
esophagus squamous epithelium	UBERON:0006920	78.25	gold quality
rectum	UBERON:0001052	78.06	gold quality
mucosa of transverse colon	UBERON:0004991	77.86	gold quality
right testis	UBERON:0004534	77.79	gold quality
left testis	UBERON:0004533	77.67	gold quality
adrenal tissue	UBERON:0018303	75.68	gold quality
gingival epithelium	UBERON:0001949	75.67	gold quality
thymus	UBERON:0002370	75.30	gold quality
lymph node	UBERON:0000029	74.88	gold quality
esophagus mucosa	UBERON:0002469	74.56	gold quality
caecum	UBERON:0001153	73.83	gold quality
epithelium of esophagus	UBERON:0001976	73.83	gold quality
oral cavity	UBERON:0000167	73.80	gold quality
squamous epithelium	UBERON:0006914	73.26	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	963.15
E-HCAD-56	yes	474.19
E-MTAB-11121	yes	363.77
E-GEOD-99795	yes	295.01
E-HCAD-13	yes	22.07
E-ANND-3	yes	5.16
E-MTAB-6911	no	548.71
E-CURD-11	no	542.66
E-MTAB-6524	no	235.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, REL, TXK

miRNA regulators (miRDB)

20 targeting DLGAP5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 38)

• results strongly suggest that HURP is a potential novel cell cycle regulator that may play a role in the carcinogenesis of human cancer cells (PMID:12527899)
• Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis is regulated by Fbx7 and the SCF complex (PMID:15145941)
• KIAA0008 expression is associated with invasiveness of HCC; overexpression of KIAA0008 leads to a more invasive phenotype of HCC cell lines. (PMID:15340842)
• HURP is a potential oncogenic target of Aurora-A. (PMID:15987997)
• HURP controls spindle stability and dynamics to achieve efficient kinetochore capture at prometaphase, timely chromosome congression to the metaphase plate, and proper interkinetochore tension for anaphase initiation. (PMID:16769820)
• Dlg7 has a role in stem cell survival, in maintaining stem cell properties, and in carcinogenesis. (PMID:17322106)
• Phosphorylation of HURP by Aurora A provides a regulatory mechanism for the control of spindle assembly and function. (PMID:18321990)
• Combined expression of DLG7 and PINK1 was the best predictor of disease free survival in malignant adrenal cortex neoplasms. (PMID:19139432)
• HURP regulates Kif18A localization and dynamics at the plus end of kinetochore microtubules. (PMID:21924616)
• Hepatocellular carcinoma patients can be separated into three prognosis-distinguishable groups by use of a risk score that is based upon HURP expression. (PMID:22022601)
• DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. (PMID:22048964)
• Knockdown of HURP inhibits the proliferation of hepacellular carcinoma cells via downregulation of gankyrin and accumulation of p53. (PMID:22230478)
• HURP is a substrate of Aurora kinase A, which plays a crucial role in the stabilization of kinetochore fiber (PMID:23610398)
• RNA purification using functionalized MNPs was 97%. CONCLUSIONS: The developed colorimetric HURP RNA AuNP assay is sensitive, simple, and can aid noninvasive diagnosis of bladder cancer (PMID:24183881)
• The expression of DLGAP5 is regulated by methylation; the up-regulation of DLGAP5 contributes to hepatocellular carcinoma tumorigenesis by promoting cell proliferation. (PMID:24324629)
• expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP. (PMID:24349376)
• Detection of urinary HURP RNA is a useful for early detection of bladder cancer and bilharzial bladder cancer. (PMID:24375315)
• Aurora-A/HURP relays cell transforming signal to NF-kappaB, and the HURP/NF-kappaB complex is engaged in the regulation of cyclin E1 expression. (PMID:25289861)
• Data provide evidence for the involvement of HURP protein in the modulation of prostate cancer cell resistance to gamma irradiation via mechanism mediated by the ubiquitination of ATM and p53. (PMID:26505164)
• Elevated NEK2, DLGAP5 and ECT2 expression was negatively correlated with both overall survival (OS) and relapse-free survival (RFS). (PMID:28808310)
• The bioinformatic analysis suggests that HURP promotes carcinogenesis in multiple manners. Taken together, we revealed the prognostic value of HURP in nonsmall cell lung cancer (NSCLC)patients and HURP may be a potential therapeutic target for NSCLC. (PMID:29484418)
• HURP recruits TACC3 to regulate K-fiber formation and support chromosome congression. (PMID:30054275)
• DLGAP5 has a unique function in stabilizing spindle formation and surviving microtubule assault from docetaxel, in an androgen-regulated cell cycle system. (PMID:30341281)
• Study provides evidence that downregulation of NUSAP1 can inhibit the proliferation, migration, and invasion of IBC cells by regulating CDK1 and DLGAP5 expression and enhances the drug susceptibility to E-ADM. (PMID:30476929)
• DLG7/DLGAP5 represents a potential biomarker for colorectal cancer. (PMID:31286215)
• positive expression of DLGAP5 in prostate cancer tissues correlates with poor prognosis of patients and has a role in castration-resistant prostate cancer cell growth and migration. (PMID:31454442)
• Spindle-Length-Dependent HURP Localization Allows Centrosomes to Control Kinetochore-Fiber Plus-End Dynamics. (PMID:31668617)
• The expression of hepatoma upregulated protein in human endometrium during the menstrual cycle. (PMID:32840162)
• Ran-GTP Is Non-essential to Activate NuMA for Mitotic Spindle-Pole Focusing but Dynamically Polarizes HURP Near Chromosomes. (PMID:33186548)
• Screening and identification of LMNB1 and DLGAP5, two key biomarkers in gliomas. (PMID:33956061)
• Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression. (PMID:34687756)
• Whole Genome Transcriptomic Analysis of Ovary Granulosa Cells Revealed an Anti-Apoptosis Regulatory Gene DLGAP5 in Polycystic Ovary Syndrome. (PMID:35370991)
• DLGAP5 knockdown inactivates the Wnt/beta-catenin signal to repress endometrial cancer cell malignant activities. (PMID:36454672)
• High Expression of DLGAP5 Indicates Poor Prognosis and Immunotherapy in Lung Adenocarcinoma and Promotes Proliferation through Regulation of the Cell Cycle. (PMID:36712920)
• circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557. (PMID:37334578)
• DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP. (PMID:37421434)
• DLGAP5 triggers proliferation and metastasis of bladder cancer by stabilizing E2F1 via USP11. (PMID:38182895)
• DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target. (PMID:38414025)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dlgap5	ENSDARG00000045167
mus_musculus	Dlgap5	ENSMUSG00000037544
rattus_norvegicus	Dlgap5	ENSRNOG00000010721
drosophila_melanogaster	mars	FBGN0033845

Paralogs (4): DLGAP4 (ENSG00000080845), DLGAP3 (ENSG00000116544), DLGAP1 (ENSG00000170579), DLGAP2 (ENSG00000198010)

Protein

Protein identifiers

Disks large-associated protein 5 — Q15398 (reviewed: Q15398)

Alternative names: Discs large homolog 7, Disks large-associated protein DLG7, Hepatoma up-regulated protein

All UniProt accessions (3): Q15398, G3V4E5, G3V543

UniProt curated annotations — full annotation on UniProt →

Function. Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells. Mitotic phosphoprotein regulated by the ubiquitin-proteasome pathway. Key regulator of adherens junction integrity and differentiation that may be involved in CDH1-mediated adhesion and signaling in epithelial cells.

Subunit / interactions. Interacts with CDK1. Interacts with the C-terminal proline-rich region of FBXO7. Recruited by FBXO7 to a SCF (SKP1-CUL1-F-box) protein complex in a CDK1/Cyclin B-phosphorylation dependent manner. Interacts with CDH1.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Abundantly expressed in fetal liver. Expressed at lower levels in bone marrow, testis, colon, and placenta.

Post-translational modifications. Ubiquitinated, leading to its degradation. Decreased phosphorylation levels are associated with the differentiation of intestinal epithelial cells.

Similarity. Belongs to the SAPAP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15398-2	1	yes
Q15398-1	2
Q15398-3	3

RefSeq proteins (2): NP_001139487, NP_055565* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005026	SAPAP	Family

Pfam: PF03359

UniProt features (44 total): modified residue 24, compositionally biased region 6, sequence variant 4, region of interest 2, splice variant 2, sequence conflict 2, chain 1, coiled-coil region 1, cross-link 1, helix 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7ZX4	X-RAY DIFFRACTION	2.08
9DUQ	ELECTRON MICROSCOPY	2.8
9DHZ	ELECTRON MICROSCOPY	3.1
8X9P	ELECTRON MICROSCOPY	3.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15398-F1	56.52	0.18

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 (25): 67, 202, 326, 329, 338, 401, 402, 618, 627, 629, 634, 639, 642, 662, 725, 757, 759, 774, 777, 784 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription

MSigDB gene sets: 986 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_SIGNALING_BY_NOTCH, MODULE_52, GCM_MAP4K4, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT

GO Biological Process (8): mitotic spindle organization (GO:0007052), chromosome segregation (GO:0007059), mitotic chromosome movement towards spindle pole (GO:0007079), regulation of mitotic cell cycle (GO:0007346), signaling (GO:0023052), positive regulation of mitotic metaphase/anaphase transition (GO:0045842), kinetochore assembly (GO:0051382), centrosome localization (GO:0051642)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), spindle pole centrosome (GO:0031616), mitotic spindle (GO:0072686), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by NOTCH3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	3
cellular anatomical structure	2
intracellular membraneless organelle	2
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell cycle process	1
mitotic sister chromatid segregation	1
chromosome movement towards spindle pole	1
mitotic cell cycle process	1
regulation of cell cycle	1
regulation of biological process	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic metaphase/anaphase transition	1
positive regulation of mitotic nuclear division	1
positive regulation of mitotic sister chromatid separation	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of metaphase/anaphase transition of cell cycle	1
kinetochore organization	1
protein-containing complex assembly	1
membraneless organelle assembly	1
microtubule organizing center localization	1
tubulin binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
spindle pole	1
centrosome	1
spindle	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLGAP5	KIF11	P52732	922
DLGAP5	TPX2	Q9ULW0	831
DLGAP5	AURKB	Q96GD4	818
DLGAP5	MELK	Q14680	813
DLGAP5	ASPM	Q8IZT6	799
DLGAP5	CCNB2	O95067	791
DLGAP5	CEP55	Q53EZ4	755
DLGAP5	TOP2A	P11388	754
DLGAP5	NUSAP1	Q9BXS6	753
DLGAP5	BUB1	O43683	752
DLGAP5	AURKA	O14965	747
DLGAP5	BUB1B	O60566	746
DLGAP5	CENPF	P49454	743
DLGAP5	KIF4A	O95239	742
DLGAP5	KIF20A	O95235	741

IntAct

69 interactions, top by confidence:

A	B	Type	Score
DLGAP5	KPNB1	psi-mi:“MI:0914”(association)	0.730
CLTC	DLGAP5	psi-mi:“MI:0915”(physical association)	0.650
CLTC	DLGAP5	psi-mi:“MI:0407”(direct interaction)	0.650
TUBA1B	TXNDC9	psi-mi:“MI:0914”(association)	0.640
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
RAN	RGPD8	psi-mi:“MI:0914”(association)	0.640
RACK1	RIOK3	psi-mi:“MI:0914”(association)	0.640
GOLGA2	DLGAP5	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	DLGAP5	psi-mi:“MI:0915”(physical association)	0.560
DLGAP5	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
DYDC2	INPPL1	psi-mi:“MI:0914”(association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
B2M	KPNA3	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
CAPSL	DLGAP5	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PURG	U2SURP	psi-mi:“MI:0914”(association)	0.530
NPM1	WDR46	psi-mi:“MI:0914”(association)	0.480
EPS15	DLGAP5	psi-mi:“MI:0407”(direct interaction)	0.440
DLGAP5	FRMD8P1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (95): DLGAP5 (Two-hybrid), MTUS2 (Two-hybrid), DLGAP5 (Two-hybrid), DLGAP5 (Two-hybrid), DLGAP5 (Affinity Capture-MS), DLGAP5 (Reconstituted Complex), DLGAP5 (Proximity Label-MS), DLGAP5 (Proximity Label-MS), KPNB1 (Affinity Capture-MS), DLGAP5 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), DLGAP5 (Affinity Capture-MS), DLGAP5 (Affinity Capture-MS), DLGAP5 (Affinity Capture-MS), DLGAP5 (Affinity Capture-MS)

ESM2 similar proteins: A0JMT0, A0JMZ1, A1L2F3, A1L3I5, A5D7U0, A8PUI7, A9C3N6, O13024, O14216, O60293, O75167, P53352, P86345, P86346, P86347, Q0IHP2, Q0P5H2, Q0V9F7, Q15398, Q1W1G1, Q24595, Q2YDJ0, Q32N93, Q3KPK4, Q3KQW7, Q4KLP8, Q4V7H8, Q53HL2, Q563C3, Q5BKG8, Q5RBS5, Q5XG21, Q5XLR4, Q5ZJU5, Q6CK38, Q6CNI5, Q6FME9, Q6GLC7, Q76FK4, Q7K3L1

Diamond homologs: B1AZP2, O14490, O95886, P97836, P97837, P97838, P97839, Q15398, Q6PFD5, Q7K3L1, Q7ZYZ6, Q8BJ42, Q8K4R9, Q9D415, Q9P1A6, Q9Y2H0

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
AURKA	“up-regulates quantity by stabilization”	DLGAP5	phosphorylation
DLGAP5	“up-regulates activity”	DLG4	binding
DLGAP5	“up-regulates activity”	SHANK1	relocalization
DLGAP5	“up-regulates activity”	SHANK2	relocalization
DLGAP5	“up-regulates activity”	SHANK3	relocalization
FBXO7	“down-regulates quantity by destabilization”	DLGAP5	binding
SCF-FBW7	“down-regulates quantity by destabilization”	DLGAP5	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	72.5×	1e-08
Transport of connexons to the plasma membrane	6	72.5×	1e-08
Gap junction trafficking and regulation	6	63.4×	2e-08
Gap junction trafficking	6	63.4×	2e-08
Post-chaperonin tubulin folding pathway	6	63.4×	2e-08
Formation of tubulin folding intermediates by CCT/TriC	6	56.4×	3e-08
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	6	54.4×	4e-08
Activation of AMPK downstream of NMDARs	6	50.8×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	5	60.8×	3e-06
mitotic cell cycle	9	18.2×	6e-07
ribosomal small subunit biogenesis	5	17.2×	1e-03
microtubule cytoskeleton organization	8	14.7×	1e-05
cytoplasmic translation	5	14.0×	3e-03
protein import into nucleus	5	10.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	218
Likely benign	32
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1340842	GRCh37/hg19 3q29(chr3:196897651-197081796)x1	Pathogenic
562864	GRCh37/hg19 3q29(chr3:195703615-197348575)x1	Pathogenic
816511	GRCh37/hg19 3q29(chr3:195652973-197346971)x1	Pathogenic

SpliceAI

8224 predictions. Top by Δscore:

Variant	Effect	Δscore
14:55150791:AAACT:A	donor_loss	1.0000
14:55150792:AACT:A	donor_loss	1.0000
14:55150793:ACT:A	donor_loss	1.0000
14:55150794:CTT:C	donor_loss	1.0000
14:55150795:TT:T	donor_loss	1.0000
14:55150796:TACT:T	donor_loss	1.0000
14:55150797:A:AC	donor_gain	1.0000
14:55150797:A:T	donor_loss	1.0000
14:55150798:C:CA	donor_gain	1.0000
14:55150798:CTGA:C	donor_gain	1.0000
14:55150798:CTGAA:C	donor_gain	1.0000
14:55150844:TAGTT:T	acceptor_gain	1.0000
14:55150845:AGTTC:A	acceptor_loss	1.0000
14:55150846:GTT:G	acceptor_gain	1.0000
14:55150848:TC:T	acceptor_loss	1.0000
14:55150849:C:CC	acceptor_gain	1.0000
14:55150849:CTG:C	acceptor_loss	1.0000
14:55150850:T:G	acceptor_loss	1.0000
14:55151689:TCTCA:T	donor_loss	1.0000
14:55151690:CTCAC:C	donor_loss	1.0000
14:55151691:TCA:T	donor_loss	1.0000
14:55151692:CAC:C	donor_loss	1.0000
14:55151694:C:CT	donor_loss	1.0000
14:55151694:CCTGA:C	donor_gain	1.0000
14:55151770:T:C	donor_gain	1.0000
14:55151778:T:TA	donor_gain	1.0000
14:55151938:CAAC:C	acceptor_gain	1.0000
14:55151940:AC:A	acceptor_gain	1.0000
14:55151940:ACC:A	acceptor_loss	1.0000
14:55151941:CC:C	acceptor_gain	1.0000

AlphaMissense

5603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:55169420:A:C	F509L	0.996
14:55169420:A:T	F509L	0.996
14:55169422:A:G	F509L	0.996
14:55169430:A:G	L506P	0.994
14:55170738:A:G	W451R	0.993
14:55170738:A:T	W451R	0.993
14:55163021:A:G	W535R	0.992
14:55163021:A:T	W535R	0.992
14:55169417:C:A	W510C	0.992
14:55169417:C:G	W510C	0.992
14:55169520:A:G	L476P	0.992
14:55169419:A:G	W510R	0.991
14:55169419:A:T	W510R	0.991
14:55169492:A:C	F485L	0.991
14:55169492:A:T	F485L	0.991
14:55169494:A:G	F485L	0.991
14:55169430:A:T	L506Q	0.990
14:55169421:A:G	F509S	0.989
14:55169517:A:G	L477P	0.988
14:55183698:T:A	K98N	0.988
14:55183698:T:G	K98N	0.988
14:55169493:A:G	F485S	0.987
14:55183684:A:G	L103P	0.987
14:55158568:G:C	F609L	0.986
14:55158568:G:T	F609L	0.986
14:55158570:A:G	F609L	0.986
14:55163044:A:G	L527P	0.986
14:55169532:C:T	G472D	0.986
14:55175348:G:C	F433L	0.986
14:55175348:G:T	F433L	0.986

dbSNP variants (sampled 300 via entrez): RS1000024557 (14:55155829 C>T), RS1000158824 (14:55159317 TAAG>T), RS1000176051 (14:55153268 C>T), RS1000180046 (14:55162353 C>T), RS1000211073 (14:55162520 G>A), RS1000252185 (14:55191486 C>A,T), RS1000318715 (14:55188354 T>C), RS1000352245 (14:55155492 A>C,G,T), RS1000373998 (14:55167938 C>G), RS1000481072 (14:55155615 T>C), RS1000512726 (14:55160807 G>A,T), RS1000545163 (14:55161191 A>C,G), RS1000592952 (14:55190028 T>C,G), RS1000625332 (14:55190358 G>A), RS1000634914 (14:55152230 T>A,C)

Disease associations

OMIM: gene MIM:617859 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Brugada syndrome	Limited	Unknown
cleft lip/palate	Limited	Autosomal dominant

Mondo (2): Brugada syndrome (MONDO:0015263), cleft lip/palate (MONDO:0016044)

Orphanet (1): Orofacial clefting syndrome (Orphanet:139039)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001711_2	Protein biomarker	2.000000e-188
GCST002550_5	Allergic rhinitis	1.000000e-08
GCST004635_27	Testicular germ cell tumor	3.000000e-08
GCST006630_58	Diastolic blood pressure	8.000000e-12
GCST006979_314	Heel bone mineral density	3.000000e-12
GCST009391_1189	Metabolite levels	5.000000e-06
GCST010320_100	PR interval	7.000000e-09
GCST010321_208	PR interval	1.000000e-09
GCST90000025_684	Appendicular lean mass	1.000000e-10
GCST90020025_1038	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1861	Waist-hip index	1.000000e-08
GCST90020029_728	Waist circumference adjusted for body mass index	5.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0021575	adipic acid measurement
EFO:0004462	PR interval
EFO:0004980	appendicular lean mass
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	5
Cisplatin	affects expression, decreases reaction, increases expression, decreases expression	4
Cyclosporine	decreases expression	4
bisphenol A	affects localization, decreases expression, affects expression	3
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
cobaltous chloride	decreases expression	2
Zoledronic Acid	decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Doxorubicin	decreases expression	2
Estradiol	increases expression	2
Quercetin	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tunicamycin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, affects expression	2
Genistein	affects expression, decreases expression	2
Vitamin K 3	affects expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
chloroacetaldehyde	affects expression	1
propionaldehyde	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1

Clinical trials (associated diseases)

123 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
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT02933437	PHASE2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT07146880	PHASE2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT02014961	Not specified	UNKNOWN	Worm Study: Modifier Genes in Sudden Cardiac Death
NCT02052765	Not specified	COMPLETED	AnalyST & Brugada Syndrome - Feasibility Study
NCT02302274	Not specified	COMPLETED	Diagnostic Value and Safety of Flecainide Infusion Test in Brugada Syndrome
NCT02344277	Not specified	COMPLETED	Evaluation of Subcutaneous Implantable Cardiac Defibrillator in Brugada Patients
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02641431	Not specified	COMPLETED	Epicardial Ablation in Brugada Syndrome
NCT02704416	Not specified	COMPLETED	Ablation in Brugada Syndrome for the Prevention of VF
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03435393	Not specified	UNKNOWN	Ripple Mapping for Epicardial Mapping of Brugada Syndrome
NCT03485508	Not specified	UNKNOWN	The Brugada Syndrome: a Follow-up Study
NCT03491475	Not specified	UNKNOWN	Echocardiography During Ajmaline Test
NCT03524079	Not specified	COMPLETED	Right Ventricle Morphology and Hemodynamics in BrS
NCT03764592	Not specified	COMPLETED	VF Mapping in Brugada and Early Repolarization Syndromes
NCT03775954	Not specified	RECRUITING	Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT03992677	Not specified	COMPLETED	Feasibility of Improving Risk Stratification in Brugada Syndrome
NCT04124237	Not specified	COMPLETED	Long Term Monitoring for Risk of Sudden Death
NCT04232787	Not specified	UNKNOWN	Southeast Asian Brugada Syndrome Cohort
NCT04257994	Not specified	RECRUITING	Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
NCT04420078	Not specified	COMPLETED	Brugada Ablation of VF Substrate Ongoing MultiCenter Registry
NCT04580992	Not specified	UNKNOWN	Defining the Electrocardiographic Effect of Propofol on the Ajmaline Provocation Drug Challenge: A Prospective Trial
NCT04650009	Not specified	COMPLETED	Physical Activity in Children With Inherited Cardiac Diseases
NCT04712136	Not specified	COMPLETED	Healthy-related Quality of Life and Physical Activity of Children With Cardiac Malformations
NCT04808193	Not specified	UNKNOWN	European Perioperative Brugada Survey
NCT05048602	Not specified	UNKNOWN	Drug-induced Brugada Syndrome Research Database
NCT05274646	Not specified	COMPLETED	Impact on Risk Stratification of Overlap Syndrome Phenotype in Patients With E1784K Mutation in SCN5A
NCT05283759	Not specified	RECRUITING	UZ Brussel HRMC Registry of Brugada Syndrome
NCT05521451	Not specified	RECRUITING	Clinical Cohort Study - TRUST
NCT05643209	Not specified	RECRUITING	Brugada Syndrome Substrate Characterization and Ablation
NCT05685134	Not specified	COMPLETED	Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome