DEPDC5

Summary

DEPDC5 (DEP domain containing 5, GATOR1 subcomplex subunit, HGNC:18423) is a protein-coding gene on chromosome 22q12.2-q12.3, encoding GATOR1 complex protein DEPDC5 (O75140). As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9681 — RefSeq curated summary.

At a glance

• Gene–disease (curated): focal epilepsy (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 2,806 total — 303 pathogenic, 137 likely-pathogenic
• Phenotypes (HPO): 126
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001242896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18423
Approved symbol	DEPDC5
Name	DEP domain containing 5, GATOR1 subcomplex subunit
Location	22q12.2-q12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0645, DEP.5
Ensembl gene	ENSG00000100150
Ensembl biotype	protein_coding
OMIM	614191
Entrez	9681

Gene structure

Transcript identifiers

Ensembl transcripts: 76 — 39 protein_coding, 18 retained_intron, 14 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000382111, ENST00000382112, ENST00000400242, ENST00000400246, ENST00000400248, ENST00000400249, ENST00000433147, ENST00000437411, ENST00000448753, ENST00000456178, ENST00000458532, ENST00000462414, ENST00000469969, ENST00000469974, ENST00000471914, ENST00000473802, ENST00000479261, ENST00000490731, ENST00000494060, ENST00000497340, ENST00000535622, ENST00000642212, ENST00000642551, ENST00000642605, ENST00000642684, ENST00000642696, ENST00000642771, ENST00000642915, ENST00000642956, ENST00000642974, ENST00000643021, ENST00000643075, ENST00000643097, ENST00000643166, ENST00000643395, ENST00000643751, ENST00000643948, ENST00000644162, ENST00000644331, ENST00000644690, ENST00000645015, ENST00000645407, ENST00000645494, ENST00000645547, ENST00000645560, ENST00000645564, ENST00000645693, ENST00000645711, ENST00000645755, ENST00000645785, ENST00000645893, ENST00000645967, ENST00000646135, ENST00000646383, ENST00000646465, ENST00000646515, ENST00000646755, ENST00000646830, ENST00000646969, ENST00000646998, ENST00000647289, ENST00000647343, ENST00000647438, ENST00000651528, ENST00000903727, ENST00000903728, ENST00000903729, ENST00000915004, ENST00000915005, ENST00000915006, ENST00000915007, ENST00000915008, ENST00000915009, ENST00000915010, ENST00000915011, ENST00000960437

RefSeq mRNA: 13 — MANE Select: NM_001242896 NM_001007188, NM_001136029, NM_001242896, NM_001242897, NM_001363852, NM_001363854, NM_001364318, NM_001364319, NM_001364320, NM_001369901, NM_001369902, NM_001369903, NM_014662

CCDS: CCDS43006, CCDS43007, CCDS46692, CCDS56229, CCDS74849, CCDS87017, CCDS87018, CCDS93151

Canonical transcript exons

ENST00000651528 — 43 exons

Exon	Start	End
ENSE00000653307	31778099	31778168
ENSE00000653308	31783907	31783985
ENSE00000653309	31784814	31784875
ENSE00000653316	31804162	31804223
ENSE00000653318	31806122	31806191
ENSE00000653319	31809611	31809647
ENSE00000653322	31814992	31815212
ENSE00000653323	31819022	31819225
ENSE00000653324	31821502	31821637
ENSE00000653326	31833915	31833980
ENSE00000653331	31843645	31843812
ENSE00000653332	31845018	31845237
ENSE00000653333	31846834	31846967
ENSE00000879948	31758546	31758633
ENSE00000879950	31822693	31822790
ENSE00001167463	31754862	31754979
ENSE00001332142	31810521	31810641
ENSE00001332145	31804842	31804915
ENSE00001490948	31861368	31861433
ENSE00001490980	31836972	31837155
ENSE00003465839	31843095	31843212
ENSE00003485807	31792745	31792817
ENSE00003500185	31838685	31838845
ENSE00003532975	31764975	31765060
ENSE00003534604	31802704	31802838
ENSE00003556686	31876157	31876265
ENSE00003562908	31874273	31874405
ENSE00003569463	31879525	31879752
ENSE00003574498	31905984	31906066
ENSE00003579387	31901742	31901802
ENSE00003579891	31873255	31873332
ENSE00003612808	31893582	31893751
ENSE00003614751	31870590	31870744
ENSE00003615928	31797600	31797703
ENSE00003639456	31857445	31857553
ENSE00003647795	31760656	31760702
ENSE00003650130	31766585	31766668
ENSE00003672317	31768814	31768863
ENSE00003675273	31798582	31798656
ENSE00003684192	31897482	31897653
ENSE00003685435	31792033	31792102
ENSE00003818087	31906205	31908033
ENSE00003828198	31754019	31754164

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 93.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9675 / max 77.9198, expressed in 1592 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191829	5.4042	1591
191831	0.3339	62
191832	0.1547	22
191830	0.0747	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	93.18	gold quality
frontal pole	UBERON:0002795	92.51	gold quality
middle frontal gyrus	UBERON:0002702	92.14	gold quality
colonic epithelium	UBERON:0000397	91.96	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.82	gold quality
ventricular zone	UBERON:0003053	88.42	gold quality
sural nerve	UBERON:0015488	88.40	gold quality
cortical plate	UBERON:0005343	87.99	gold quality
adrenal tissue	UBERON:0018303	87.50	gold quality
endometrium epithelium	UBERON:0004811	87.35	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.06	gold quality
mucosa of transverse colon	UBERON:0004991	86.93	gold quality
calcaneal tendon	UBERON:0003701	86.91	gold quality
lower esophagus mucosa	UBERON:0035834	85.64	gold quality
ganglionic eminence	UBERON:0004023	85.18	gold quality
right lobe of liver	UBERON:0001114	84.24	gold quality
prefrontal cortex	UBERON:0000451	84.09	gold quality
left ovary	UBERON:0002119	83.80	gold quality
granulocyte	CL:0000094	83.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.61	gold quality
right ovary	UBERON:0002118	83.42	gold quality
right uterine tube	UBERON:0001302	83.39	gold quality
tonsil	UBERON:0002372	83.17	gold quality
monocyte	CL:0000576	82.94	gold quality
leukocyte	CL:0000738	82.84	gold quality
mononuclear cell	CL:0000842	82.64	gold quality
right frontal lobe	UBERON:0002810	82.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.01	gold quality
ovary	UBERON:0000992	81.73	gold quality
spleen	UBERON:0002106	81.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.74
E-MTAB-7303	no	276.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6

miRNA regulators (miRDB)

62 targeting DEPDC5, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. (PMID:21725309)
• Mutations in DEPDC5 cause familial focal epilepsy with variable foci. (PMID:23542697)
• Mutations in DEPDC5 cause familial focal epilepsy with variable foci. (PMID:23542701)
• A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population. (PMID:24283814)
• DEPDC5 mutations are associated with both lesional and nonlesional epilepsies. (PMID:24585383)
• Mutations in DEPDC5 are associated with childhood focal epilepsies. (PMID:24591017)
• DEPDC5 loss-of-function mutations may represent a part of the broader familial focal epilepsy with variable foci phenotype found in 30 European families with a presentation of autosomal dominant nocturnal frontal lobe epilepsy. (PMID:24814846)
• PAPL, IL10RB and DEPDC5 polymorphisms have an impact on progression of hepatitis B virus-related liver disease. (PMID:25032264)
• This chapter focuses on DEPDC5, a newly identified gene in autosomal dominant focal epilepsies [review] (PMID:25194487)
• The effects of 10 DEPDC5 variants identified in individuals with focal epilepsy and two DEPDC5 variants identified in serous ovarian tumors, on TORC1 signaling and GATOR-1 complex formation. (PMID:25366275)
• Genetic variations in DEPDC5 gene region may influence HCV-associated liver cirrhosis and/or hepatocellular carcinoma. development. (PMID:25551790)
• An association was made for DEPDC5 with sporadic focal cortical dysplasia and also hemimegalencephaly. (PMID:25599672)
• Truncating DEPDC5 mutations were found in all four French families with focal cortical dysplasia and focal epilepsy. (PMID:25623524)
• MICA and DEPDC5 SNPs were found to be strongly associated with HCV-induced HCC. (PMID:25764692)
• This revealed four patients to have two or more tumors that were clonally related, all of which lacked MED12 mutations. DEPDC5 was discovered as a novel tumor suppressor gene playing a role in the progression of uterine leiomyomas. (PMID:25964426)
• This study found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies. (PMID:26216793)
• DEPDC5 variants increase fibrosis progression in European subjects with chronic HCV infection. Our findings suggest that DEPDC5 down-regulation may contribute to HCV-related fibrosis by increasing MMP2 synthesis through the beta-catenin pathway (PMID:26517016)
• This cohort study showed DEPDC5 mutations were present in 8% of individuals with focal epilepsy, including one individual with focal cortical dysplasia. (PMID:27173016)
• Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research. (PMID:28170089)
• This study showed that polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with with chronic hepatitis C-related hepatocellular carcinoma development in Japanese patients with chronic hepatitis C virus infection. (PMID:28928439)
• Heterozygous mice appeared to be normal and we found no evidence of increased susceptibility to seizures or tumorigenesis. Together, these data support mTORC1 hyperactivation as the likely pathogenic mechanism that underpins DEPDC5 loss of function in humans and highlights the potential utility of mTORC1 inhibitors in the treatment of DEPDC5-associated epilepsy (PMID:28974734)
• the DEPDC5-KO HCC cells could acquire anti-oxidant ability through p62 accumulation and survive under leucine starvation, and that downregulated DEPDC5 expression was an independent predictive factor for patient outcome. (PMID:29311600)
• Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy. (PMID:29708508)
• Knockout of either TSC1 or DEPDC5 led to enhanced HIV-1 reactivation in both a T-cell and a monocyte cell lines. (PMID:30087333)
• overall, 63 distinct variants were identified: 53 in DEPDC5, three in NPRL2 and seven in NPRL3 . Among these, 46 were novel (including 39 single nucleotide variants and seven CNVs) and 16 were newly defined as recurrent variants; 34 were loss-of-function (LoF) variants (nonsense, splice-site, frameshift indels and CNVs). (PMID:30093711)
• There was a significant correlation between DEPDC5 rs1012068A/C and HBV-related hepatocellular carcinoma in the Han Chinese population. A to C mutation increased the risk of the developing of HBV-related hepatocellular carcinoma. (PMID:30683632)
• A variant in the MICA gene is associated with liver fibrosis progression in chronic hepatitis C through TGF-beta1 dependent mechanisms. (PMID:30723271)
• our data provide the first evidence of behavioral alterations in mice with Depdc5 loss and support mTOR inhibition as a rational therapeutic strategy for DEPDC5-related epilepsy in humans. (PMID:31174205)
• findings of recurrent genomic alterations, together with functional data, validate the DEPDC5 as a bona fide tumor suppressor contributing to GIST progression and a biologically relevant target of the frequent chromosome 22q deletions (PMID:31636198)
• Sleep-related hypermotor epilepsy (SHE): Contribution of known genes in 103 patients. (PMID:31835056)
• Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes. (PMID:32086284)
• DEPDC5 haploinsufficiency drives increased mTORC1 signaling and abnormal morphology in human iPSC-derived cortical neurons. (PMID:32574724)
• GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families: A possible gradient in severity? (PMID:33461085)
• [Genotype and phenotype of children with DEPDC5 gene variants related epilepsy]. (PMID:34587683)
• DEPDC5-related epilepsy: A comprehensive review. (PMID:35429726)
• Disheveled EGL-10 and pleckstrin domain-containing 5 rs1012068 T/G gene polymorphism among Egyptian chronic HCV-infected patients: disease progression and related complications. (PMID:35758967)
• Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria. (PMID:36067010)
• Clinical and genetic features of GATOR1 complex-associated epilepsy. (PMID:36604176)
• Clinical Course May Be Independent from Neuroimaging in DEPDC-5-Related Epilepsy. (PMID:37003255)
• Seizure features and outcomes in 50 children with GATOR1 variants: A retrospective study, more favorable for epilepsy surgery. (PMID:37259768)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	depdc5	ENSDARG00000078105
mus_musculus	Depdc5	ENSMUSG00000037426
rattus_norvegicus	Depdc5	ENSRNOG00000018144
drosophila_melanogaster	Iml1	FBGN0035227
caenorhabditis_elegans		WBGENE00011604

Protein

Protein identifiers

GATOR1 complex protein DEPDC5 — O75140 (reviewed: O75140)

Alternative names: DEP domain-containing protein 5

All UniProt accessions (28): O75140, A0A2R8Y5E9, A0A2R8Y5K9, A0A2R8Y5P2, A0A2R8Y5T1, A0A2R8Y5V3, A0A2R8Y6F4, A0A2R8Y6H3, A0A2R8Y6H8, A0A2R8Y6V4, A0A2R8Y6Y2, A0A2R8Y721, A0A2R8Y7C9, A0A2R8Y7U0, A0A2R8Y7U6, A0A2R8Y7X0, A0A2R8Y842, A0A2R8YEI8, A0A2R8YET0, A0A2R8YEW8, A0A2R8YF97, A0A2R8YFS1, A0A5F9UWT1, C9JGS4, F8WAX3, H0Y770, H7C1T0, H7C3I3

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway. Within the GATOR1 complex, DEPDC5 mediates direct interaction with the nucleotide-binding pocket of small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and coordinates their nucleotide loading states by promoting RagA/RRAGA or RagB/RRAGB into their GDP-binding state and RagC/RRAGC or RagD/RRAGD into their GTP-binding state. However, it does not execute the GAP activity, which is mediated by NPRL2.

Subunit / interactions. Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction of the GATOR complex with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) heterodimers. Interacts with SAMTOR; interaction is direct and takes place in presence of methionine, leading to inhibit the activity of the GATOR1 complex.

Subcellular location. Lysosome membrane. Cytoplasm. Cytosol. Perinuclear region.

Tissue specificity. Expressed in developing and adult brain.

Post-translational modifications. Phosphorylation at Ser-1002 and Ser-1530 by AKT1 and PIM1 inhibit the activity of DEPDC5, releasing inhibition of the mTORC1 pathway. Ubiquitinated. Amino acid-induced ‘Lys-48’-linked polyubiquitination of DEPDC5 by the BCR(KLHL22) ubiquitin ligase complex leads to DEPDC5 proteasomal degradation and inhibition of the GATOR1 complex. Ubiquitination may occur at multiple lysines.

Disease relevance. Epilepsy, familial focal, with variable foci 1 (FFEVF1) [MIM:604364] An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 111 (DEE111) [MIM:620504] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE111 is an autosomal recessive form characterized by the onset of seizures in the first days, months, or years of life. Brain imaging shows frontal, parietal, and perisylvian polymicrogyria, dysmorphic basal ganglia and corpus callosum, and hypoplastic pons. Death in early childhood may occur. The disease is caused by variants affecting the gene represented in this entry. Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins, including DEPDC5, are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal.

Domain organisation. The DEP domain mediates the interaction with KLHL22.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the IML1 family.

Isoforms (8)

UniProt ID	Names	Canonical?
O75140-10	10	yes
O75140-2	2
O75140-4	4
O75140-5	5
O75140-6	6
O75140-8	8
O75140-9	9
O75140-1	1

RefSeq proteins (13): NP_001007189, NP_001129501, NP_001229825, NP_001229826, NP_001350781, NP_001350783, NP_001351247, NP_001351248, NP_001351249, NP_001356830, NP_001356831, NP_001356832, NP_055477 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000591	DEP_dom	Domain
IPR027244	IML1	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045838	DEPDC5_CTD	Domain
IPR048255	IML1_N	Domain
IPR055213	IML1_double_psi_beta_barrel	Domain

Pfam: PF00610, PF12257, PF19418, PF23013

UniProt features (146 total): strand 44, helix 27, mutagenesis site 23, sequence variant 19, splice variant 8, turn 7, compositionally biased region 6, region of interest 4, modified residue 3, sequence conflict 3, chain 1, domain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9V0J	ELECTRON MICROSCOPY	2.97
8FW5	ELECTRON MICROSCOPY	3.08
9O5A	ELECTRON MICROSCOPY	3.2
9O5D	ELECTRON MICROSCOPY	3.34
9XZY	ELECTRON MICROSCOPY	3.8
7T3B	ELECTRON MICROSCOPY	3.9
6CES	ELECTRON MICROSCOPY	4
7T3A	ELECTRON MICROSCOPY	4
7T3C	ELECTRON MICROSCOPY	4
6CET	ELECTRON MICROSCOPY	4.4
9O5E	ELECTRON MICROSCOPY	5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75140-F1	65.22	0.19

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): 505, 1002, 1530

Mutagenesis-validated functional residues (23):

Position	Phenotype
185–189	in mutant ab; abolished interaction with nprl2 and nprl3; when associated with 371-g–g-375.
371–375	in mutant ab; abolished interaction with nprl2 and nprl3; when associated with 185-g–g-189.
447	no effect on ubiquitination. loss of interaction with klhl22 and ubiquitination; when associated with r-710, r-1065, r-1
710	no effect on ubiquitination. loss of interaction with klhl22 and ubiquitination; when associated with r-447, r-1065, r-1
775–779	in mutant p; strongly decreased interaction with raga/rraga.
775	strongly decreased interaction with raga/rraga.
1002	abolished phosphorylation by pim1; when associated with a-1530.
1065	no effect on ubiquitination. loss of interaction with klhl22 and ubiquitination; when associated with r-447, r-710, r-10
1088	no effect on ubiquitination. loss of interaction with klhl22 and ubiquitination; when associated with r-447, r-710, r-10
1188	no effect on interaction with klhl22.
1189	no effect on interaction with klhl22.
1195	no effect on interaction with klhl22.
1201	no effect on interaction with klhl22.
1203	no effect on interaction with klhl22.
1207	no effect on interaction with klhl22.
1223	no effect on interaction with klhl22.
1241	no effect on interaction with klhl22.
1244	no effect on interaction with klhl22.
1250	no effect on interaction with klhl22.
1253	no effect on interaction with klhl22.
1256	no effect on interaction with klhl22.
1530	abolished phosphorylation by pim1; when associated with a-1002.
1574	no effect on ubiquitination. loss of ubiquitination; when associated with r-447, r-710, r-1065 and r-1088.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9639288	Amino acids regulate mTORC1

MSigDB gene sets: 377 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOCC_VACUOLAR_MEMBRANE, GOMF_GTPASE_BINDING, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TOR_SIGNALING, MORF_IL4, MODULE_99, GOBP_CELLULAR_RESPONSE_TO_STARVATION, GOBP_TOR_SIGNALING, MORF_ATF2, GOBP_POSITIVE_REGULATION_OF_AUTOPHAGY, SCHLOSSER_SERUM_RESPONSE_UP

GO Biological Process (11): positive regulation of autophagy (GO:0010508), cellular response to amino acid starvation (GO:0034198), intracellular signal transduction (GO:0035556), negative regulation of TORC1 signaling (GO:1904262), cytoplasmic translation (GO:0002181), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202), negative regulation of translational initiation (GO:0045947), positive regulation of translational initiation (GO:0045948), protein localization to lysosome (GO:0061462), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (4): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (8): lysosome (GO:0005764), lysosomal membrane (GO:0005765), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), GATOR1 complex (GO:1990130), cytoplasm (GO:0005737), membrane (GO:0016020), Cul3-RING ubiquitin ligase complex (GO:0031463)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
TORC1 signaling	2
regulation of TORC1 signaling	2
translational initiation	2
regulation of translational initiation	2
binding	2
cytoplasm	2
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
cellular response to starvation	1
response to amino acid starvation	1
signal transduction	1
negative regulation of TOR signaling	1
translation	1
response to nutrient levels	1
cellular response to stimulus	1
TOR signaling	1
negative regulation of translation	1
positive regulation of translation	1
protein localization to vacuole	1
positive regulation of TOR signaling	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
protein-containing complex	1
Seh1-associated complex	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEPDC5	NPRL2	Q8WTW4	998
DEPDC5	NPRL3	Q12980	998
DEPDC5	WDR59	Q6PJI9	858
DEPDC5	ITFG2	Q969R8	818
DEPDC5	WDR24	Q96S15	817
DEPDC5	MIOS	Q9NXC5	809
DEPDC5	KICS2	Q96MD2	780
DEPDC5	SZT2	Q5T011	776
DEPDC5	SEH1L	Q96EE3	773
DEPDC5	KPTN	Q9Y664	753
DEPDC5	SEC13	P55735	733
DEPDC5	SAMTOR	Q1RMZ1	707
DEPDC5	RRAGA	Q7L523	701
DEPDC5	KCNT1	Q5JUK3	696
DEPDC5	RRAGB	Q5VZM2	692

IntAct

25 interactions, top by confidence:

A	B	Type	Score
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
NPRL2	DEPDC5	psi-mi:“MI:0914”(association)	0.730
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
SAMTOR	DEPDC5	psi-mi:“MI:0914”(association)	0.640
SZT2	DEPDC5	psi-mi:“MI:0914”(association)	0.530
DEPDC5	NPRL3	psi-mi:“MI:0914”(association)	0.530
NPRL3	DEPDC5	psi-mi:“MI:0914”(association)	0.530
NPRL2	ZBTB5	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SAMTOR	PER1	psi-mi:“MI:0914”(association)	0.530
ITFG2	DEPDC5	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DEPDC5	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
Sesn2	CASTOR2	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
SAMTOR	MIF4GD	psi-mi:“MI:0914”(association)	0.350
DEPDC5	SZT2	psi-mi:“MI:0914”(association)	0.350
DEPDC5	GLA	psi-mi:“MI:0914”(association)	0.350
NPRL2	APAF1	psi-mi:“MI:0914”(association)	0.350
GLA	DEPDC5	psi-mi:“MI:0914”(association)	0.350
CDC5L	DEPDC5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (132): DEPDC5 (Affinity Capture-MS), DEPDC5 (Affinity Capture-MS), DEPDC5 (Affinity Capture-Western), DEPDC5 (Affinity Capture-Western), RRAGC (Affinity Capture-Western), RRAGA (Affinity Capture-Western), NPRL3 (Affinity Capture-Western), RRAGC (Reconstituted Complex), RRAGB (Reconstituted Complex), DEPDC5 (Affinity Capture-Western), DEPDC5 (Affinity Capture-Western), DEPDC5 (Affinity Capture-MS), DEPDC5 (Affinity Capture-MS), SZT2 (Affinity Capture-MS), C12orf66 (Affinity Capture-MS)

ESM2 similar proteins: A1CEE0, A1DFV9, A1DG01, A2QQ79, A4R596, B0XVV1, B2AR36, C4Y5P7, C7YM38, G2WWH6, I1RQE2, O74788, O75140, P0CO32, P0CO33, P0CP70, P0CP71, P19970, P61460, P87233, Q01513, Q01631, Q09033, Q0CHV5, Q0UY20, Q1DN93, Q1E9Q9, Q2GSA4, Q2H0S0, Q2UMR9, Q4PBL3, Q4PE51, Q4WHD1, Q4WHH4, Q52EB3, Q5AIA4, Q5AW24, Q6CAP3, Q6CWI2, Q6E3D2

Diamond homologs: A1CEE0, A1DFV9, A4R596, O75140, P61460, Q0CHV5, Q1E9Q9, Q2H0S0, Q2UMR9, Q4WHH4, Q54XA2, Q5AW24, Q69ZK0, Q7S9J6, Q8TCU6, Q9W0E3, Q570Y9, Q8TB45, Q8WZA2, Q4PE51, P0CO32, P0CO33, Q05AS8, Q3LAC4, Q70Z35, Q9EQZ6, A3LRB2, P47170, Q5AIA4, Q6CAP3, Q6CWI2, Q6FK84

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DEPDC5	“form complex”	GATOR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
Amino acids regulate mTORC1	6	66.8×	5e-08
Cellular responses to stress	5	10.2×	5e-03
Cellular responses to stimuli	5	8.7×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of TORC1 signaling	7	108.0×	3e-11
cellular response to amino acid starvation	5	75.7×	4e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

2806 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	303
Likely pathogenic	137
Uncertain significance	1212
Likely benign	858
Benign	128

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012693	NM_001242896.3(DEPDC5):c.675del (p.Tyr226fs)	Pathogenic
1068966	NM_001242896.3(DEPDC5):c.800G>A (p.Trp267Ter)	Pathogenic
1069166	NC_000022.10:g.(?32160941)(32161066_?)del	Pathogenic
1069167	NC_000022.10:g.(?32179873)(32179991_?)del	Pathogenic
1069168	NC_000022.10:g.(?32180780)(32302503_?)del	Pathogenic
1069222	NM_001242896.3(DEPDC5):c.2275_2281del (p.Tyr759fs)	Pathogenic
1069249	NM_001242896.3(DEPDC5):c.158del (p.Leu53fs)	Pathogenic
1069270	NM_001242896.3(DEPDC5):c.208_209del (p.Asp70fs)	Pathogenic
1069325	NM_001242896.3(DEPDC5):c.2196dup (p.Val733fs)	Pathogenic
1069373	NM_001242896.3(DEPDC5):c.2548dup (p.Asp850fs)	Pathogenic
1069404	NM_001242896.3(DEPDC5):c.3205C>T (p.Gln1069Ter)	Pathogenic
1070245	NM_001242896.3(DEPDC5):c.4290del (p.Tyr1431fs)	Pathogenic
1070712	NM_001242896.3(DEPDC5):c.4671_4672del (p.Trp1558fs)	Pathogenic
1070820	NM_001242896.3(DEPDC5):c.2958_2959insTTTTTTTTTTTTTTTTNNNNNNNNNNTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCAGGCTGGAGTGCAGTGGCGGGATCTCGGCTCACTGCAAGCTCCGCCTCCTGGATGGTTTT (p.Val987delinsPhePhePhePhePheXaaXaaXaaXaaPhePhePhePhePhePhePhePhePheTer)	Pathogenic
1071232	NM_001242896.3(DEPDC5):c.3578del (p.Leu1193fs)	Pathogenic
1071236	NM_001242896.3(DEPDC5):c.862del (p.Glu288fs)	Pathogenic
1071273	NC_000022.10:g.(?32188019)(32194642_?)del	Pathogenic
1071274	NC_000022.10:g.(?32205577)(32206647_?)del	Pathogenic
1071275	NC_000022.10:g.(?32150888)(32188823_?)del	Pathogenic
1071348	NM_001242896.3(DEPDC5):c.2898C>A (p.Cys966Ter)	Pathogenic
1072903	NM_001242896.3(DEPDC5):c.2094dup (p.Ser699fs)	Pathogenic
1073135	NM_001242896.3(DEPDC5):c.3449_3450del (p.Glu1150fs)	Pathogenic
1073159	NM_001242896.3(DEPDC5):c.280-2A>G	Pathogenic
1073184	NC_000022.10:g.(?32150888)(32162674_?)del	Pathogenic
1073185	NC_000022.10:g.(?32150888)(32164869_?)del	Pathogenic
1073186	NC_000022.10:g.(?32301960)(32302483_?)del	Pathogenic
1073187	NC_000022.10:g.(?32174065)(32180881_?)del	Pathogenic
1073664	NM_001242896.3(DEPDC5):c.247C>T (p.Gln83Ter)	Pathogenic
1073683	NM_001242896.3(DEPDC5):c.305dup (p.Leu102fs)	Pathogenic
1074181	NM_001242896.3(DEPDC5):c.2489_2511del (p.Leu830fs)	Pathogenic

SpliceAI

6716 predictions. Top by Δscore:

Variant	Effect	Δscore
22:31758544:A:AG	acceptor_gain	1.0000
22:31758545:G:GG	acceptor_gain	1.0000
22:31758630:ACAGG:A	donor_loss	1.0000
22:31758632:AGGT:A	donor_loss	1.0000
22:31758634:G:GA	donor_loss	1.0000
22:31758634:G:GG	donor_gain	1.0000
22:31758635:T:A	donor_loss	1.0000
22:31760654:A:AG	acceptor_gain	1.0000
22:31760655:G:GA	acceptor_gain	1.0000
22:31760655:GC:G	acceptor_gain	1.0000
22:31760655:GCC:G	acceptor_gain	1.0000
22:31760655:GCCCT:G	acceptor_gain	1.0000
22:31760698:GAAGG:G	donor_gain	1.0000
22:31760701:GG:G	donor_gain	1.0000
22:31760701:GGGTA:G	donor_loss	1.0000
22:31760702:GG:G	donor_gain	1.0000
22:31760702:GGTA:G	donor_loss	1.0000
22:31760703:GTAAG:G	donor_loss	1.0000
22:31760704:T:TC	donor_loss	1.0000
22:31764970:TTTA:T	acceptor_loss	1.0000
22:31764971:TTAG:T	acceptor_loss	1.0000
22:31764972:TA:T	acceptor_loss	1.0000
22:31764973:A:AG	acceptor_gain	1.0000
22:31764974:G:GA	acceptor_gain	1.0000
22:31764974:GA:G	acceptor_gain	1.0000
22:31764974:GAA:G	acceptor_gain	1.0000
22:31764974:GAAA:G	acceptor_gain	1.0000
22:31764974:GAAAC:G	acceptor_gain	1.0000
22:31765031:G:GT	donor_gain	1.0000
22:31765061:G:GA	donor_loss	1.0000

AlphaMissense

10618 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:31765035:T:A	V85D	1.000
22:31766601:T:C	L99P	1.000
22:31766655:T:C	L117P	1.000
22:31778116:T:C	L144P	1.000
22:31783955:A:C	S178R	1.000
22:31783957:C:A	S178R	1.000
22:31783957:C:G	S178R	1.000
22:31783967:T:A	W182R	1.000
22:31783967:T:C	W182R	1.000
22:31784834:G:C	A195P	1.000
22:31784859:T:C	L203P	1.000
22:31784870:T:A	W207R	1.000
22:31784870:T:C	W207R	1.000
22:31792064:T:A	V219D	1.000
22:31797631:T:A	W267R	1.000
22:31797631:T:C	W267R	1.000
22:31798620:G:A	G304R	1.000
22:31798620:G:C	G304R	1.000
22:31798643:T:A	N311K	1.000
22:31798643:T:G	N311K	1.000
22:31798645:T:C	L312P	1.000
22:31802745:G:A	G330R	1.000
22:31802745:G:C	G330R	1.000
22:31802745:G:T	G330W	1.000
22:31802746:G:A	G330E	1.000
22:31802772:G:T	G339W	1.000
22:31802819:G:C	K354N	1.000
22:31802819:G:T	K354N	1.000
22:31802824:G:C	R356P	1.000
22:31804162:G:A	G361E	1.000

dbSNP variants (sampled 300 via entrez): RS1000074858 (22:31776908 T>C), RS1000079437 (22:31777156 C>T), RS1000100429 (22:31820858 A>C,G), RS1000144071 (22:31856767 G>A), RS1000145644 (22:31882758 C>A,T), RS1000151667 (22:31755201 A>G), RS1000160973 (22:31796550 A>T), RS1000161895 (22:31885898 G>T), RS1000170120 (22:31754771 G>A,T), RS1000193333 (22:31903564 T>A,C,G), RS1000234275 (22:31772031 C>A,T), RS1000238547 (22:31801642 G>C), RS1000240551 (22:31845991 A>G), RS1000256546 (22:31886724 C>T), RS1000270496 (22:31839150 G>A)

Disease associations

OMIM: gene MIM:614191 | disease phenotypes: MIM:604364, MIM:620504, MIM:618744, MIM:600513, MIM:117100, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy, familial focal, with variable foci 1	Definitive	Autosomal dominant
developmental and epileptic encephalopathy 111	Strong	Autosomal dominant
autosomal dominant epilepsy with auditory features	Supportive	Autosomal dominant
autosomal dominant nocturnal frontal lobe epilepsy	Supportive	Autosomal dominant
familial focal epilepsy with variable foci	Supportive	Autosomal dominant
Brugada syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
focal epilepsy	Definitive	AD

Mondo (17): familial focal epilepsy with variable foci (MONDO:0020310), epilepsy, familial focal, with variable foci 1 (MONDO:0024556), developmental and epileptic encephalopathy 111 (MONDO:0957780), developmental and epileptic encephalopathy, 83 (MONDO:0032895), focal epilepsy (MONDO:0005384), familial sleep-related hypermotor epilepsy (MONDO:0000030), epilepsy (MONDO:0005027), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), epilepsy syndrome (MONDO:0015650), intellectual disability (MONDO:0001071), genetic developmental and epileptic encephalopathy (MONDO:0100062), hereditary ataxia (MONDO:0100309), cerebral cortical dysplasia (MONDO:0017094), ependymoma (MONDO:0016698), Brugada syndrome (MONDO:0015263)

Orphanet (8): Familial focal epilepsy with variable foci (Orphanet:98820), Sleep-related hypermotor epilepsy (Orphanet:98784), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Epilepsy syndrome (Orphanet:166463), Hereditary ataxia (Orphanet:183518), Cerebral cortical dysplasia (Orphanet:268950), Ependymoma (Orphanet:251636), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

126 total (30 of 126 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000546	Retinal degeneration
HP:0000574	Thick eyebrow
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000648	Optic atrophy
HP:0000666	Horizontal nystagmus
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001139_1	Chronic hepatitis C infection	1.000000e-13
GCST001428_12	Intelligence	5.000000e-07
GCST002491_16	Age-related hearing impairment	2.000000e-06
GCST004250_28	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	6.000000e-07
GCST006484_22	Type 2 diabetes	3.000000e-07
GCST009212_15	Isthmus-cingulate cortex volume	8.000000e-06
GCST010135_20	Oily fish consumption	3.000000e-10
GCST010135_5	Oily fish consumption	1.000000e-15
GCST010140_12	Pork consumption	3.000000e-10
GCST010140_49	Pork consumption	1.000000e-15
GCST010142_11	Fish- and plant-related diet	1.000000e-11
GCST010142_79	Fish- and plant-related diet	3.000000e-08
GCST011500_3	Gastroesophageal reflux disease, peptic ulcer disease and/or corresponding medications and treatment	1.000000e-08
GCST90002385_579	High light scatter reticulocyte count	8.000000e-14
GCST90002386_493	High light scatter reticulocyte percentage of red cells	7.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0007965	response to combination chemotherapy
EFO:0008111	diet measurement
EFO:0009923	Peptic ulcer and gastro-oesophageal reflux disease (GORD) drug use measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
D004828	Epilepsies, Partial	C10.228.140.490.360
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D054220	Malformations of Cortical Development	C10.500.507; C16.131.666.507
C537297	Autosomal Dominant Lateral Temporal Lobe Epilepsy (supp.)
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)
C565785	Epilepsy, Partial, with Variable Foci (supp.)
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation, increases mutagenesis	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
Tetrachlorodibenzodioxin	affects expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
glycidyl methacrylate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Dieldrin	increases response to substance	1
Gallic Acid	increases expression, decreases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Sodium Selenite	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

7 cell lines: 3 cancer cell line, 3 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1F2	Abcam A-549 DEPDC5 KO	Cancer cell line	Male
CVCL_C1SV	CIPi003-A	Induced pluripotent stem cell	Female
CVCL_D9D6	Ubigene HEK293 DEPDC5 KO	Transformed cell line	Female
CVCL_SK74	HAP1 DEPDC5 (-) 1	Cancer cell line	Male
CVCL_SK75	HAP1 DEPDC5 (-) 2	Cancer cell line	Male
CVCL_WN90	INSRMi002-A	Induced pluripotent stem cell	Male
CVCL_WR06	INSRMi006-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

342 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
NCT00438451	PHASE4	COMPLETED	Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00855738	PHASE4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT00955357	PHASE4	COMPLETED	Trial to Assess Lacosamide as the First add-on Anti-epileptic Drug Treatment in Patients With Partial-onset Seizures
NCT01190098	PHASE4	COMPLETED	Randomized Controlled Trial to Assess Effects of Lacosamide on Sleep and Wake in Adults With Focal Epilepsy
NCT01235403	PHASE4	COMPLETED	Trial to Assess Optimized Dosage of Lacosamide as add-on Therapy in Patients With Partial Onset Seizure
NCT02208492	PHASE4	COMPLETED	The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study
NCT03607851	PHASE4	COMPLETED	Efficacy and Safety of Rapid Titration Protocols of Lacosamide
NCT05748236	PHASE4	UNKNOWN	The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy
NCT07193277	PHASE4	RECRUITING	Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy
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
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