COBLL1

Summary

COBLL1 (cordon-bleu WH2 repeat protein like 1, HGNC:23571) is a protein-coding gene on chromosome 2q24.3, encoding Cordon-bleu protein-like 1 (Q53SF7).

Enables cadherin binding activity. Located in extracellular exosome.

Source: NCBI Gene 22837 — RefSeq curated summary.

At a glance

• GWAS associations: 290
• Clinical variants (ClinVar): 229 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_001365672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23571
Approved symbol	COBLL1
Name	cordon-bleu WH2 repeat protein like 1
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0977
Ensembl gene	ENSG00000082438
Ensembl biotype	protein_coding
OMIM	610318
Entrez	22837

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 35 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000342193, ENST00000375458, ENST00000409184, ENST00000414843, ENST00000434366, ENST00000439313, ENST00000444537, ENST00000445474, ENST00000448708, ENST00000452626, ENST00000456171, ENST00000456693, ENST00000460238, ENST00000474975, ENST00000480873, ENST00000483743, ENST00000489955, ENST00000491126, ENST00000493713, ENST00000493868, ENST00000493921, ENST00000495084, ENST00000496396, ENST00000629362, ENST00000652658, ENST00000861276, ENST00000861277, ENST00000861278, ENST00000861279, ENST00000861280, ENST00000861281, ENST00000861282, ENST00000861283, ENST00000861284, ENST00000861285, ENST00000861286, ENST00000861287, ENST00000861288, ENST00000926847, ENST00000926848, ENST00000926849, ENST00000926850, ENST00000946162, ENST00000946163, ENST00000946164, ENST00000946165

RefSeq mRNA: 10 — MANE Select: NM_001365672 NM_001278458, NM_001278460, NM_001278461, NM_001365670, NM_001365671, NM_001365672, NM_001365673, NM_001365674, NM_001365675, NM_014900

CCDS: CCDS2223, CCDS63045, CCDS63046, CCDS92884

Canonical transcript exons

ENST00000652658 — 14 exons

Exon	Start	End
ENSE00000779621	164722425	164722522
ENSE00000779622	164727969	164728197
ENSE00000779623	164729914	164730115
ENSE00001611366	164680188	164686032
ENSE00001753629	164841710	164841823
ENSE00003466713	164699405	164699499
ENSE00003478737	164704952	164705105
ENSE00003499620	164694269	164695836
ENSE00003543411	164841156	164841246
ENSE00003583503	164700522	164700756
ENSE00003624993	164743687	164743875
ENSE00003635911	164722075	164722311
ENSE00003638921	164692221	164692397
ENSE00003648954	164704444	164704518

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0024 / max 647.8117, expressed in 1468 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31637	3.9600	921
31635	2.1668	745
31632	1.7550	700
31639	1.5827	723
31634	1.0294	389
31640	0.5842	321
31633	0.4967	234
31624	0.4402	63
31626	0.3174	60
31636	0.2474	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.06	gold quality
placenta	UBERON:0001987	97.01	gold quality
adrenal tissue	UBERON:0018303	96.40	gold quality
renal medulla	UBERON:0000362	96.02	gold quality
left adrenal gland	UBERON:0001234	95.97	gold quality
oral cavity	UBERON:0000167	95.94	gold quality
right adrenal gland	UBERON:0001233	95.79	gold quality
metanephros cortex	UBERON:0010533	95.77	gold quality
right adrenal gland cortex	UBERON:0035827	95.68	gold quality
left adrenal gland cortex	UBERON:0035825	95.63	gold quality
adrenal gland	UBERON:0002369	95.47	gold quality
cauda epididymis	UBERON:0004360	95.39	gold quality
adrenal cortex	UBERON:0001235	95.00	gold quality
secondary oocyte	CL:0000655	94.96	gold quality
calcaneal tendon	UBERON:0003701	94.77	gold quality
corpus epididymis	UBERON:0004359	94.63	gold quality
body of pancreas	UBERON:0001150	93.97	gold quality
liver	UBERON:0002107	93.97	gold quality
blood vessel layer	UBERON:0004797	93.80	gold quality
esophagus squamous epithelium	UBERON:0006920	93.80	gold quality
parietal pleura	UBERON:0002400	93.56	gold quality
popliteal artery	UBERON:0002250	93.40	gold quality
tibial artery	UBERON:0007610	93.39	gold quality
oocyte	CL:0000023	93.28	gold quality
adult mammalian kidney	UBERON:0000082	92.84	gold quality
epithelium of esophagus	UBERON:0001976	92.79	gold quality
seminal vesicle	UBERON:0000998	92.62	gold quality
kidney	UBERON:0002113	92.54	gold quality
skin of hip	UBERON:0001554	92.24	gold quality
adipose tissue	UBERON:0001013	92.22	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	6792.98
E-CURD-119	yes	6519.41
E-HCAD-35	yes	895.62
E-MTAB-6701	yes	40.12
E-HCAD-10	yes	21.22
E-ANND-3	yes	18.61
E-MTAB-9388	yes	11.09
E-MTAB-6678	yes	6.81
E-GEOD-84465	yes	6.24
E-CURD-135	no	2338.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

230 targeting COBLL1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-539-3P	99.98	70.74	1616
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487

Literature-anchored findings (GeneRIF, showing 14)

• The gene ratio test with the COBLL1/ARHGDIA genes for survival of patients with malignant pleural mesothelioma has robust predictive value. (PMID:19401544)
• We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. (PMID:21569526)
• genetic association study in children/adolescents in Sardinia: Data suggest that an SNP in COBLL1 (rs7607980; TC or CC) is associated with lower insulin resistance and lower serum insulin levels in overweight/obese children/adolescents. (PMID:23463496)
• Aggregation of rare variants in COBLL1were nominally associated with higher waist-to-hip ratio in European-Americans. (PMID:26757982)
• The expression of COBLL1, LPL, and ZAP70 corresponded to patient prognosis and to IGHV mutational status, although not absolutely. When we combined all three markers together and performed the ROC analysis, AUC increased compared to the AUC of individual gene expression. (PMID:27185377)
• High-level expression of Cobll1 promotes the transformation of CML and generates drug resistance by increasing IKKgamma stability, which results in activation of the canonical NF-kappaB pathway. (PMID:28232743)
• polymorphism, rs7607980 of COBLL1 didnot show any significant association with T2D (PMID:28258026)
• identified COBLL1 as a novel interaction partner of ROR1 (PMID:29122990)
• nuclear COBLL1 interacts with AR to enhance complex formation with CDK1 and facilitates AR phosphorylation for genomic binding in castration-resistant prostate cancer model cells. (PMID:29686105)
• Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia. (PMID:35352878)
• Metabolic Effects of the Waist-To-Hip Ratio Associated Locus GRB14/COBLL1 Are Related to GRB14 Expression in Adipose Tissue. (PMID:35955692)
• Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes. (PMID:36493769)
• Gene-Nutrient Interactions in Obesity: COBLL1 Genetic Variants Interact with Dietary Fat Intake to Modulate the Incidence of Obesity. (PMID:36835164)
• A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes. (PMID:37253881)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cobll1a	ENSDARG00000089858
danio_rerio	cobll1b	ENSDARG00000102829
mus_musculus	Cobll1	ENSMUSG00000034903
rattus_norvegicus	Cobll1	ENSRNOG00000027016

Paralogs (1): COBL (ENSG00000106078)

Protein

Protein identifiers

Cordon-bleu protein-like 1 — Q53SF7 (reviewed: Q53SF7)

All UniProt accessions (13): Q53SF7, A0A0B4J1Z0, A0A0D9SG04, A0A0X1KG75, A0A7P0T9X3, A0A7P0TAB9, A0A7P0TAY7, C9J5Y6, C9J8C4, C9JAU3, C9JK90, C9JWZ0, F8WEK0

UniProt curated annotations — full annotation on UniProt →

Isoforms (3)

UniProt ID	Names	Canonical?
Q53SF7-4	4	yes
Q53SF7-2	2
Q53SF7-3	3

RefSeq proteins (10): NP_001265387, NP_001265389, NP_001265390, NP_001352599, NP_001352600, NP_001352601, NP_001352602, NP_001352603, NP_001352604, NP_055715 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR019025	Cordon-bleu_ubiquitin_domain	Domain
IPR039895	COBL-like	Family

Pfam: PF09469

UniProt features (65 total): modified residue 28, compositionally biased region 8, region of interest 8, sequence conflict 6, strand 5, splice variant 3, short sequence motif 2, helix 2, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DAJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53SF7-F1	50.51	0.12

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 (28): 139, 204, 222, 256, 260, 273, 284, 326, 333, 344, 356, 438, 441, 461, 471, 474, 563, 584, 786, 813 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 325 (showing top): TAATAAT_MIR126, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOZGIT_ESR1_TARGETS_DN, HASLINGER_B_CLL_WITH_MUTATED_VH_GENES, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, WANG_LMO4_TARGETS_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G23_DN, chr2q24, WTGAAAT_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOMF_ACTIN_BINDING, BASAKI_YBX1_TARGETS_DN

GO Biological Process (0):

GO Molecular Function (4): actin monomer binding (GO:0003785), cadherin binding (GO:0045296), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (3): cell cortex (GO:0005938), membrane (GO:0016020), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin binding	1
cell adhesion molecule binding	1
cytoskeletal protein binding	1
binding	1
cytoplasm	1
cell periphery	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1167 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COBLL1	GRB14	Q14449	700
COBLL1	LYPLAL1	Q5VWZ2	613
COBLL1	PPM1N	Q8N819	519
COBLL1	BLTP3A	Q6BDS2	476
COBLL1	C5orf67	F2Z3F1	448
COBLL1	ARL15	Q9NXU5	447
COBLL1	TYW1B	Q6NUM6	447
COBLL1	SLC38A11	Q08AI6	419
COBLL1	ZNF664	Q8N3J9	419
COBLL1	COBL	O75128	417
COBLL1	PPP1R3B	Q86XI6	402
COBLL1	CCDC92	Q53HC0	400
COBLL1	FAM13A	O94988	395
COBLL1	PHLDB2	Q86SQ0	395
COBLL1	RSPO3	Q9BXY4	389

IntAct

57 interactions, top by confidence:

A	B	Type	Score
PACSIN1	COBL	psi-mi:“MI:0914”(association)	0.750
PACSIN2	COBL	psi-mi:“MI:0914”(association)	0.740
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
PACSIN1	COBLL1	psi-mi:“MI:0914”(association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
PACSIN3	COBL	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PACSIN2	COBLL1	psi-mi:“MI:0914”(association)	0.530
PACSIN3	COBLL1	psi-mi:“MI:0914”(association)	0.530
COBLL1		psi-mi:“MI:0915”(physical association)	0.370
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
MAPK1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
	SDCBP	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
ILF3	RPS3A	psi-mi:“MI:0914”(association)	0.350
PACSIN2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PACSIN1	WASL	psi-mi:“MI:0914”(association)	0.350
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270
EZR	PLS3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (93): COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS), COBLL1 (Affinity Capture-MS)

ESM2 similar proteins: A2A995, A2ALU4, A4IGN8, A6NMK8, D3ZUI5, E1C2Q8, F1QGH6, O54931, O75128, O75363, O75410, O95425, P24275, P24588, P51827, Q1LWM5, Q1RMS0, Q1W617, Q3UHI0, Q3UMF0, Q3ZB98, Q499V8, Q53SF7, Q5JR59, Q5NBX1, Q5VWT5, Q5ZJ26, Q62394, Q66KC9, Q673G8, Q69ZL1, Q6GQV1, Q6INC4, Q6QZN6, Q6WKZ4, Q6Y685, Q7TP36, Q7TS75, Q80YN3, Q8BI29

Diamond homologs: D3ZUI5, O75128, Q3UMF0, Q53SF7, Q5NBX1, E7F568

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
Activation of BAD and translocation to mitochondria	7	148.0×	2e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	130.6×	3e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	130.6×	3e-12
Activation of BH3-only proteins	7	96.5×	2e-11
RHO GTPases activate PKNs	8	70.5×	9e-12
Intrinsic Pathway for Apoptosis	8	65.1×	2e-11
FOXO-mediated transcription	5	46.6×	1e-06
Apoptosis	9	42.0×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	40.7×	5e-05
intracellular protein localization	7	16.3×	5e-05
actin cytoskeleton organization	6	10.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	182
Likely benign	21
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1526925	GRCh37/hg19 2q24.2-24.3(chr2:161551326-167762790)	Pathogenic
4279156	GRCh37/hg19 2q24.2-24.3(chr2:162440255-166816537)x1	Pathogenic
60245	GRCh38/hg38 2q24.3(chr2:163455290-166962322)x1	Pathogenic
626293	Single allele	Pathogenic
148507	GRCh38/hg38 2q24.3(chr2:163419387-165682938)x1	Likely pathogenic
442713	GRCh37/hg19 2q24.3(chr2:165065255-166517749)	Likely pathogenic

SpliceAI

4508 predictions. Top by Δscore:

Variant	Effect	Δscore
2:164692214:GACTT:G	donor_loss	1.0000
2:164692215:ACTTA:A	donor_loss	1.0000
2:164692216:CTT:C	donor_loss	1.0000
2:164692217:TTACC:T	donor_loss	1.0000
2:164692218:TACC:T	donor_loss	1.0000
2:164692219:A:AC	donor_gain	1.0000
2:164692219:A:T	donor_loss	1.0000
2:164692219:AC:A	donor_gain	1.0000
2:164692219:ACC:A	donor_gain	1.0000
2:164692220:C:CC	donor_gain	1.0000
2:164692220:CC:C	donor_gain	1.0000
2:164692220:CCC:C	donor_gain	1.0000
2:164692220:CCCT:C	donor_gain	1.0000
2:164692393:TTTTC:T	acceptor_gain	1.0000
2:164692397:CCT:C	acceptor_loss	1.0000
2:164692398:C:CC	acceptor_gain	1.0000
2:164695834:CTA:C	acceptor_gain	1.0000
2:164699398:AACTC:A	donor_loss	1.0000
2:164699399:ACTC:A	donor_loss	1.0000
2:164699400:CTCAC:C	donor_loss	1.0000
2:164699401:T:TA	donor_loss	1.0000
2:164699402:C:CG	donor_loss	1.0000
2:164699404:C:A	donor_loss	1.0000
2:164699404:CCATT:C	donor_gain	1.0000
2:164699495:GTTCT:G	acceptor_gain	1.0000
2:164699496:TTCT:T	acceptor_gain	1.0000
2:164699497:TCTC:T	acceptor_loss	1.0000
2:164699498:CT:C	acceptor_gain	1.0000
2:164699499:TC:T	acceptor_loss	1.0000
2:164699500:C:CC	acceptor_gain	1.0000

AlphaMissense

7470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:164728103:A:T	I176K	0.999
2:164728186:T:A	R148S	0.999
2:164728186:T:G	R148S	0.999
2:164730041:A:G	L102P	0.999
2:164730082:A:C	C88W	0.999
2:164730084:A:G	C88R	0.999
2:164730086:A:G	L87P	0.999
2:164722192:C:A	R293S	0.998
2:164722192:C:G	R293S	0.998
2:164728064:A:G	L189S	0.998
2:164728124:A:T	L169H	0.998
2:164728144:T:A	R162S	0.998
2:164728144:T:G	R162S	0.998
2:164729963:A:G	L128S	0.998
2:164730083:C:T	C88Y	0.998
2:164743696:A:T	V74D	0.998
2:164743738:A:G	L60P	0.998
2:164727986:G:T	A215E	0.997
2:164727992:A:G	L213S	0.997
2:164728103:A:C	I176R	0.997
2:164728145:C:G	R162T	0.997
2:164728146:T:C	R162G	0.997
2:164728184:A:T	V149E	0.997
2:164728187:C:G	R148T	0.997
2:164728188:T:C	R148G	0.997
2:164730010:A:C	F112L	0.997
2:164730010:A:T	F112L	0.997
2:164730012:A:G	F112L	0.997
2:164730041:A:T	L102Q	0.997
2:164730101:T:A	D82V	0.997

dbSNP variants (sampled 300 via entrez): RS1000005032 (2:164754167 G>T), RS1000028341 (2:164657707 A>G,T), RS1000053458 (2:164797884 T>C), RS1000083921 (2:164798240 C>T), RS1000095999 (2:164840355 T>C), RS1000109883 (2:164787448 A>T), RS1000110215 (2:164747748 C>T), RS1000115378 (2:164703704 C>G,T), RS1000145590 (2:164684548 T>A), RS1000158581 (2:164690158 T>A), RS1000169326 (2:164779290 G>A), RS1000195513 (2:164770362 T>C), RS1000196437 (2:164773105 T>C), RS1000211406 (2:164839504 G>T), RS1000213787 (2:164682335 G>T)

Disease associations

OMIM: gene MIM:610318 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): epilepsy (MONDO:0005027)

Orphanet (0):

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000220	Velopharyngeal insufficiency
HP:0000327	Hypoplasia of the maxilla
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000689	Dental malocclusion
HP:0000750	Delayed speech and language development
HP:0001611	Hypernasal speech
HP:0002033	Poor suck
HP:0004395	Malnutrition
HP:0006292	Abnormality of dental eruption
HP:0006342	Peg-shaped maxillary lateral incisors
HP:0008872	Feeding difficulties in infancy
HP:0009088	Speech articulation difficulties
HP:0010294	Palate fistula
HP:0011044	Abnormal number of permanent teeth
HP:0100334	Unilateral cleft palate
HP:0100337	Bilateral cleft palate
HP:0200136	Oral-pharyngeal dysphagia
HP:0200153	Agenesis of lateral incisor

GWAS associations

290 associations (top):

Study	Trait	p-value
GCST000635_36	Response to statin therapy	6.000000e-06
GCST000755_46	HDL cholesterol	3.000000e-10
GCST000758_1	Triglycerides	2.000000e-10
GCST001526_6	Fasting blood insulin (BMI interaction)	4.000000e-20
GCST001954_4	Waist-hip ratio	3.000000e-08
GCST002063_8	Sexual dimorphism in anthropometric traits	6.000000e-16
GCST002223_24	HDL cholesterol	2.000000e-15
GCST002579_8	Heschl’s gyrus morphology	2.000000e-06
GCST002782_100	Waist-to-hip ratio adjusted for body mass index	2.000000e-29
GCST002782_101	Waist-to-hip ratio adjusted for body mass index	2.000000e-15
GCST002782_102	Waist-to-hip ratio adjusted for body mass index	5.000000e-31
GCST002782_103	Waist-to-hip ratio adjusted for body mass index	1.000000e-16
GCST002782_272	Waist-to-hip ratio adjusted for body mass index	4.000000e-10
GCST002782_273	Waist-to-hip ratio adjusted for body mass index	1.000000e-10
GCST002782_274	Waist-to-hip ratio adjusted for body mass index	4.000000e-23
GCST002782_275	Waist-to-hip ratio adjusted for body mass index	8.000000e-11
GCST002782_276	Waist-to-hip ratio adjusted for body mass index	4.000000e-23
GCST002782_277	Waist-to-hip ratio adjusted for body mass index	2.000000e-11
GCST002782_81	Waist-to-hip ratio adjusted for body mass index	5.000000e-30
GCST002782_82	Waist-to-hip ratio adjusted for body mass index	6.000000e-15
GCST002782_83	Waist-to-hip ratio adjusted for body mass index	2.000000e-31
GCST002782_84	Waist-to-hip ratio adjusted for body mass index	4.000000e-16
GCST002783_193	Body mass index	5.000000e-06
GCST002783_348	Body mass index	1.000000e-06
GCST003139_2	Glomerular filtration rate in chronic kidney disease	2.000000e-06
GCST003367_5	circulating leptin levels	1.000000e-06
GCST003368_5	circulating leptin levels adjusted for BMI	2.000000e-06
GCST003435_13	Body fat percentage	2.000000e-06
GCST003435_19	Body fat percentage	2.000000e-08
GCST003435_34	Body fat percentage	5.000000e-06

EFO canonical traits (35, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004340	body mass index
EFO:0004343	waist-hip ratio
EFO:0005951	sexual dimorphism
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005000	leptin measurement
EFO:0007793	BMI-adjusted leptin measurement
EFO:0007800	body fat percentage
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009767	glycine measurement
EFO:0009924	Drugs used in diabetes use measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0000195	metabolic syndrome
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004468	glucose measurement
EFO:0005413	joint damage measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	increases expression	1
coumarin	affects phosphorylation	1
ciglitazone	affects binding, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy