OGDHL

Summary

OGDHL (oxoglutarate dehydrogenase L, HGNC:25590) is a protein-coding gene on chromosome 10q11.23, encoding 2-oxoglutarate dehydrogenase-like, mitochondrial (Q9ULD0). 2-oxoglutarate dehydrogenase (E1-like) component of the 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC) which mediates the decarboxylation of alpha-ketoglutarate in the tricarboxylic acid cycle.

The protein encoded by this gene is similar to oxoglutarate dehydrogenase (OGDH) of the OGDH complex, which degrades glucose and glutamate. This gene encodes several isoforms, including some that appear to localize to mitochondria. The encoded protein down-regulates the AKT signaling cascade and can suppress the growth of cervical cancer cells.

Source: NCBI Gene 55753 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Yoon-Bellen neurodevelopmental syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 251 total — 2 pathogenic, 6 likely-pathogenic
• MANE Select transcript: NM_018245

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25590
Approved symbol	OGDHL
Name	oxoglutarate dehydrogenase L
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10851
Ensembl gene	ENSG00000197444
Ensembl biotype	protein_coding
OMIM	617513
Entrez	55753

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000374103, ENST00000419399, ENST00000432695, ENST00000471460, ENST00000490844, ENST00000496884, ENST00000852713, ENST00000852714, ENST00000852715, ENST00000852716, ENST00000852717, ENST00000852718, ENST00000852719, ENST00000852720, ENST00000852721, ENST00000852722, ENST00000917749, ENST00000967764, ENST00000967765, ENST00000967766

RefSeq mRNA: 11 — MANE Select: NM_018245 NM_001143996, NM_001143997, NM_001347819, NM_001347820, NM_001347821, NM_001347822, NM_001347823, NM_001347824, NM_001347825, NM_001347826, NM_018245

CCDS: CCDS44390, CCDS44391, CCDS7234

Canonical transcript exons

ENST00000374103 — 23 exons

Exon	Start	End
ENSE00000702965	49756776	49756946
ENSE00000702980	49749726	49749816
ENSE00000702984	49747029	49747208
ENSE00000702992	49745344	49745496
ENSE00000702998	49743994	49744122
ENSE00000703001	49742828	49742978
ENSE00000703009	49740710	49740837
ENSE00000703019	49738191	49738262
ENSE00000883717	49750839	49750985
ENSE00001220157	49737947	49738072
ENSE00001462490	49758389	49758593
ENSE00001643608	49745798	49745977
ENSE00001733087	49746750	49746878
ENSE00001733462	49739661	49739839
ENSE00001859879	49734641	49735351
ENSE00001881046	49762239	49762323
ENSE00003472604	49737786	49737858
ENSE00003495359	49736023	49736177
ENSE00003513732	49736357	49736520
ENSE00003532373	49744650	49744752
ENSE00003603724	49752638	49752740
ENSE00003654828	49752133	49752248
ENSE00003668176	49751827	49751981

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 97.49.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8930 / max 142.7232, expressed in 647 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109341	3.4024	621
109342	0.4906	171

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	97.49	gold quality
right lobe of liver	UBERON:0001114	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.03	gold quality
renal medulla	UBERON:0000362	95.73	gold quality
cerebellar hemisphere	UBERON:0002245	95.64	gold quality
cerebellar cortex	UBERON:0002129	95.61	gold quality
cerebellum	UBERON:0002037	94.82	gold quality
cerebellar vermis	UBERON:0004720	94.80	gold quality
metanephros cortex	UBERON:0010533	94.56	gold quality
kidney	UBERON:0002113	93.95	gold quality
right frontal lobe	UBERON:0002810	93.83	gold quality
pons	UBERON:0000988	93.50	gold quality
nephron tubule	UBERON:0001231	93.05	gold quality
adenohypophysis	UBERON:0002196	93.03	gold quality
pituitary gland	UBERON:0000007	92.88	gold quality
putamen	UBERON:0001874	92.77	gold quality
nucleus accumbens	UBERON:0001882	92.70	gold quality
choroid plexus epithelium	UBERON:0003911	92.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.45	gold quality
caudate nucleus	UBERON:0001873	92.43	gold quality
liver	UBERON:0002107	92.29	gold quality
cortex of kidney	UBERON:0001225	92.24	gold quality
anterior cingulate cortex	UBERON:0009835	91.94	gold quality
cingulate cortex	UBERON:0003027	91.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.88	gold quality
left lobe of thyroid gland	UBERON:0001120	91.46	gold quality
prefrontal cortex	UBERON:0000451	91.25	gold quality
right lobe of thyroid gland	UBERON:0001119	91.13	gold quality
kidney epithelium	UBERON:0004819	91.02	gold quality
hypothalamus	UBERON:0001898	90.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.48
E-GEOD-109979	no	59.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting OGDHL, 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-9-5P	100.00	72.28	2361
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-596	97.48	63.13	469
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-4632-3P	96.26	58.52	123

Literature-anchored findings (GeneRIF, showing 10)

• inactivation of OGDHL can contribute to cervical tumorigenesis via activation of the AKT signaling pathway and thus support it as an important anti-proliferative gene in cervical cancer. (PMID:23152800)
• Aberrant hypermethylation of OGDHL gene promoter in sporadic colorectal cancer. (PMID:30904169)
• A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis. (PMID:31175094)
• Low OGDHL expression is associated with Hepatocellular Carcinoma. (PMID:31781311)
• Authors identified 29 genes showing promising associations with breast cancer risk. Authors replicated the association for 2 genes, OGDHL and BRCA2, at a Bonferroni-corrected p < 0.05, by genotyping an independent set of samples from 1,628 breast cancer cases and 1,943 controls. The association for OGDHL was primarily driven by three deleterious variants (p.Val827Met, p.Pro839Leu, p.Phe836Ser; p < 0.01 for all). (PMID:31837001)
• OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism. (PMID:31899205)
• OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer. (PMID:33405394)
• Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia. (PMID:34800363)
• Silencing of OGDHL promotes liver cancer metastasis by enhancing hypoxia inducible factor 1 alpha protein stability. (PMID:36000493)
• Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. (PMID:38031187)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ogdhl	ENSDARG00000079249
mus_musculus	Ogdhl	ENSMUSG00000021913
rattus_norvegicus	Ogdhl	ENSRNOG00000019955
drosophila_melanogaster	Ogdh	FBGN0010352
drosophila_melanogaster	CG33791	FBGN0035240
caenorhabditis_elegans		WBGENE00020679

Paralogs (2): OGDH (ENSG00000105953), DHTKD1 (ENSG00000181192)

Protein

Protein identifiers

2-oxoglutarate dehydrogenase-like, mitochondrial — Q9ULD0 (reviewed: Q9ULD0)

Alternative names: 2-oxoglutarate dehydrogenase complex component E1-like, Alpha-ketoglutarate dehydrogenase-like

All UniProt accessions (1): Q9ULD0

UniProt curated annotations — full annotation on UniProt →

Function. 2-oxoglutarate dehydrogenase (E1-like) component of the 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC) which mediates the decarboxylation of alpha-ketoglutarate in the tricarboxylic acid cycle. The OGDHC complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) while reducing NAD(+) to NADH. The OGDHC complex is mainly active in the mitochondrion. Involved in the inhibition of cell proliferation and in apoptosis.

Subunit / interactions. The OGDHC complex comprises multiple copies of three catalytic enzyme components, the 2-oxoglutarate dehydrogenase (OGDH/E1), the dihydrolipoamide dehydrogenase (DLST/E2) and the dihydrolipoamide dehydrogenase (DLD/E3). OGDHL/E1-like isoenzyme may replace OGDH in the OGDHC complex in the brain. The presence of either ODGH/E1 or ODGHL/E1-like isoenzyme in the complex may depend on its tissular distribution.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Expressed in the brain and the liver.

Disease relevance. Yoon-Bellen neurodevelopmental syndrome (YOBELN) [MIM:619701] An autosomal recessive disorder characterized by global developmental delay, and variably impaired intellectual development. Additional variable features may include hypotonia, spasticity, ataxia, hearing loss, visual problems, seizures, and non-specific anomalies on brain imaging. The disease may be caused by variants affecting the gene represented in this entry. The causal relationship between OGDHL variants and Yoon-Bellen neurodevelopmetal syndrome as monogenic disease has been called into question and needs to be confirmed. Clinical disease presentation is highly heterogeneous with no cardinal phenotypic features occurring in all or most patients. Additionally, several of the reported variants appear with high minor allele frequency, are even present in a homozygous state in population databases, and familial segregation analysis is limited.

Induction. Post-transcriptionally repressed by microRNA miR-214 in cancer cells.

Similarity. Belongs to the alpha-ketoglutarate dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9ULD0-1	1	yes
Q9ULD0-2	2
Q9ULD0-3	3

RefSeq proteins (11): NP_001137468, NP_001137469, NP_001334748, NP_001334749, NP_001334750, NP_001334751, NP_001334752, NP_001334753, NP_001334754, NP_001334755, NP_060715* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001017	DH_E1	Domain
IPR005475	Transketolase-like_Pyr-bd	Domain
IPR011603	2oxoglutarate_DH_E1	Family
IPR029061	THDP-binding	Homologous_superfamily
IPR031717	ODO-1/KGD_C	Domain
IPR032106	2-oxogl_dehyd_N	Domain
IPR042179	KGD_C_sf	Homologous_superfamily

Pfam: PF00676, PF02779, PF16078, PF16870

Enzyme classification (BRENDA):

• EC 1.2.1.105 — 2-oxoglutarate dehydrogenase system (BRENDA: 28 organisms, 44 substrates, 119 inhibitors, 83 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.0025–10.1	50
COA	0.0032–0.075	11
NAD+	0.0249–0.3	11
2-OXOVALERATE	0.0063–0.0163	5
2-OXOADIPATE	0.107–0.52	2

Catalyzed reactions (Rhea), 1 shown:

• N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 2-oxoglutarate + H(+) = N(6)-[(R)-S(8)-succinyldihydrolipoyl]-L-lysyl-[protein] + CO2 (RHEA:12188)

UniProt features (40 total): sequence variant 22, binding site 11, splice variant 2, sequence conflict 2, transit peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULD0-F1	90.44	0.81

Functional residue map

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

Ligand- & substrate-binding residues (11): 431; 433; 433; 663; 130; 143; 145; 299; 398; 398; 431

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): YAATNRNNNYNATT_UNKNOWN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, USF_01, CAIRO_HEPATOBLASTOMA_DN

GO Biological Process (3): glycolytic process (GO:0006096), tricarboxylic acid cycle (GO:0006099), 2-oxoglutarate metabolic process (GO:0006103)

GO Molecular Function (6): oxoglutarate dehydrogenase (succinyl-transferring) activity (GO:0004591), thiamine pyrophosphate binding (GO:0030976), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor (GO:0016624)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), oxoglutarate dehydrogenase complex (GO:0045252)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aerobic respiration	2
cation binding	2
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
primary metabolic process	1
dicarboxylic acid metabolic process	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor	1
vitamin binding	1
anion binding	1
quaternary ammonium group binding	1
heterocyclic compound binding	1
sulfur compound binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
tricarboxylic acid cycle heteromeric enzyme complex	1
alpha-ketoacid dehydrogenase complex	1
transferase complex	1

Protein interactions and networks

STRING

2046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OGDHL	DLST	P36957	978
OGDHL	DLD	P09622	736
OGDHL	IDH3B	O43837	628
OGDHL	IDH3A	P50213	625
OGDHL	CS	O75390	606
OGDHL	IDH3G	P51553	604
OGDHL	ACO2	Q99798	591
OGDHL	MDH2	P40926	591
OGDHL	SUCLG1	P53597	580
OGDHL	FH	P07954	577
OGDHL	SUCLA2	Q9P2R7	562
OGDHL	PDHB	P11177	560
OGDHL	IDH2	P48735	547
OGDHL	IDH1	O75874	502
OGDHL	MDH1B	Q5I0G3	502

IntAct

39 interactions, top by confidence:

A	B	Type	Score
DLD	PDHX	psi-mi:“MI:0914”(association)	0.880
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
KGD4	DLD	psi-mi:“MI:0914”(association)	0.640
EMC1	EMC8	psi-mi:“MI:0914”(association)	0.640
CDK4	OGDHL	psi-mi:“MI:0915”(physical association)	0.560
OGDHL	STAT3	psi-mi:“MI:0915”(physical association)	0.510
STAT3	OGDHL	psi-mi:“MI:0915”(physical association)	0.510
SMYD1	OGDHL	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
SIAH2	OGDH	psi-mi:“MI:0914”(association)	0.350
ACBD7	FYN	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CEP135	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CEP135	WWP2	psi-mi:“MI:0914”(association)	0.350
CEP135	WDR91	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TADA2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
LIG3	TK2	psi-mi:“MI:0914”(association)	0.350
ZNF718	TRIM24	psi-mi:“MI:0914”(association)	0.350
OGDHL	HSPD1	psi-mi:“MI:0914”(association)	0.350
CATSPERE	PYGB	psi-mi:“MI:0914”(association)	0.350
ACBD7	SRC	psi-mi:“MI:0914”(association)	0.350
ARMS2	PRKCA	psi-mi:“MI:0914”(association)	0.350
KMT5B	CARS1	psi-mi:“MI:0914”(association)	0.350
TCAIM	KGD4	psi-mi:“MI:0914”(association)	0.350
DNAI3	GALM	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): OGDHL (Affinity Capture-MS), OGDHL (Affinity Capture-MS), OGDHL (Affinity Capture-MS), OGDHL (Affinity Capture-MS), OGDHL (Affinity Capture-MS), OGDHL (Biochemical Activity), OGDHL (Affinity Capture-MS), OGDHL (PCA), OGDHL (Two-hybrid), OGDHL (Affinity Capture-MS), OGDHL (Proximity Label-MS), OGDHL (Proximity Label-MS), OGDHL (Proximity Label-MS), OGDHL (Proximity Label-MS), OGDHL (Proximity Label-MS)

ESM2 similar proteins: A0PVU7, A0R0B0, A0R2B1, A1KI36, A1TDK2, A1UK81, A3Q3N5, A5U1U6, A5VSQ0, A6WXF0, A7GMD4, A7Z5J9, A9M8Q9, A9VJX9, B0CIS7, B2S877, B7HH19, B7IM94, C0RFG8, P0AFG3, P0AFG4, P0AFG5, P19543, P45303, P52647, P52965, P9WIS4, P9WIS5, Q02218, Q148N0, Q1B4V6, Q2RMD6, Q2YLS2, Q53046, Q57AX5, Q59097, Q59106, Q5L172, Q5R9L8, Q5RCB8

Diamond homologs: A0PVU7, A0R2B1, A1KI36, A1TDK2, A1UK81, A3Q3N5, A5ISU5, A5U1U6, A5VSQ0, A6QGW6, A6U1N4, A6WXF0, A7GMD4, A7X295, A7Z5J9, A8FE66, A8Z3Z0, A9M8Q9, A9VJX9, B0CIS7, B2S877, B7HH19, B7I0H2, B7IM94, B7JEU9, B9IU58, C0RFG8, C1ELG5, C3LAU3, C3P487, C4L3W2, C5D802, D3ZQD3, O61199, O74378, P0AFG3, P0AFG4, P0AFG5, P0C601, P20707

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
OGDHL	“form complex”	OGDC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	6
Uncertain significance	176
Likely benign	23
Benign	11

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1334178	NM_018245.3(OGDHL):c.2018G>A (p.Arg673Gln)	Pathogenic
1334179	NM_018245.3(OGDHL):c.1464T>C (p.Val488=)	Pathogenic
1334181	NM_018245.3(OGDHL):c.895A>G (p.Arg299Gly)	Likely pathogenic
2503805	NM_018245.3(OGDHL):c.2140+1G>A	Likely pathogenic
3065905	NM_018245.3(OGDHL):c.1862-2A>G	Likely pathogenic
402144	NM_018245.3(OGDHL):c.2333C>T (p.Ser778Leu)	Likely pathogenic
4072296	NM_018245.3(OGDHL):c.1685del (p.Asp562fs)	Likely pathogenic
4293918	NM_018245.3(OGDHL):c.1135C>T (p.Gln379Ter)	Likely pathogenic

SpliceAI

4531 predictions. Top by Δscore:

Variant	Effect	Δscore
10:49736026:ATGGG:A	donor_gain	1.0000
10:49736176:ATCT:A	acceptor_loss	1.0000
10:49736179:T:G	acceptor_loss	1.0000
10:49736518:TCC:T	acceptor_gain	1.0000
10:49736518:TCCC:T	acceptor_loss	1.0000
10:49736519:CCC:C	acceptor_gain	1.0000
10:49736520:CCT:C	acceptor_loss	1.0000
10:49736521:C:CC	acceptor_gain	1.0000
10:49736522:T:G	acceptor_loss	1.0000
10:49736530:C:CT	acceptor_gain	1.0000
10:49736530:C:T	acceptor_gain	1.0000
10:49736531:A:T	acceptor_gain	1.0000
10:49737943:TCACC:T	donor_loss	1.0000
10:49737944:CACC:C	donor_loss	1.0000
10:49737945:A:AC	donor_gain	1.0000
10:49737945:A:T	donor_loss	1.0000
10:49737945:AC:A	donor_gain	1.0000
10:49737945:ACCGG:A	donor_gain	1.0000
10:49737946:C:CG	donor_gain	1.0000
10:49737946:CC:C	donor_gain	1.0000
10:49737946:CCG:C	donor_gain	1.0000
10:49737946:CCGG:C	donor_gain	1.0000
10:49737946:CCGGC:C	donor_gain	1.0000
10:49738068:AATGC:A	acceptor_gain	1.0000
10:49738069:ATGC:A	acceptor_gain	1.0000
10:49738070:TGC:T	acceptor_gain	1.0000
10:49738071:GC:G	acceptor_gain	1.0000
10:49738071:GCCT:G	acceptor_loss	1.0000
10:49738072:CC:C	acceptor_gain	1.0000
10:49738072:CCTG:C	acceptor_loss	1.0000

AlphaMissense

6694 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:49739714:A:G	W756R	1.000
10:49739714:A:T	W756R	1.000
10:49739769:G:C	F737L	1.000
10:49739769:G:T	F737L	1.000
10:49739771:A:G	F737L	1.000
10:49739778:A:C	F734L	1.000
10:49739778:A:T	F734L	1.000
10:49739780:A:G	F734L	1.000
10:49739792:A:G	W730R	1.000
10:49739792:A:T	W730R	1.000
10:49742830:G:C	F670L	1.000
10:49742830:G:T	F670L	1.000
10:49742832:A:G	F670L	1.000
10:49745919:G:T	A452D	1.000
10:49745969:G:C	F435L	1.000
10:49745969:G:T	F435L	1.000
10:49745971:A:G	F435L	1.000
10:49746833:C:G	G405R	1.000
10:49747187:G:C	H337D	1.000
10:49750839:C:A	R299M	1.000
10:49750940:A:C	F265L	1.000
10:49750940:A:T	F265L	1.000
10:49750942:A:G	F265L	1.000
10:49737838:T:A	K846N	0.999
10:49737838:T:G	K846N	0.999
10:49737839:T:A	K846I	0.999
10:49738251:G:C	H777Q	0.999
10:49738251:G:T	H777Q	0.999
10:49738252:T:C	H777R	0.999
10:49738253:G:C	H777D	0.999

dbSNP variants (sampled 300 via entrez): RS1000193385 (10:49746156 C>A,T), RS1000211187 (10:49746343 A>T), RS1000431619 (10:49741261 G>C), RS1000580713 (10:49763225 G>A), RS1000809125 (10:49737095 A>G), RS1000881240 (10:49736612 C>T), RS1001216931 (10:49747715 G>A,C), RS1001270694 (10:49752994 C>T), RS1001370023 (10:49760432 G>A), RS1001408766 (10:49759214 C>T), RS1001681945 (10:49759833 C>A,T), RS1001744708 (10:49752814 C>T), RS1001921990 (10:49734423 A>G), RS1002017504 (10:49760994 G>A), RS1002044608 (10:49743922 C>T)

Disease associations

OMIM: gene MIM:617513 | disease phenotypes: MIM:619701

GenCC curated gene-disease

Disease	Classification	Inheritance
Yoon-Bellen neurodevelopmental syndrome	Strong	Autosomal recessive

Mondo (2): depressive disorder (MONDO:0002050), Yoon-Bellen neurodevelopmental syndrome (MONDO:0859221)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003866	Depressive Disorder	F03.600.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	5
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
entinostat	increases expression, affects cotreatment	2
Acetaminophen	increases expression, decreases expression	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
dinophysistoxin 1	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Furaldehyde	affects cotreatment, decreases expression, affects localization, increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methamphetamine	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000378	PHASE4	COMPLETED	Antidepressant Treatment of Melancholia in Late Life
NCT00004554	PHASE4	COMPLETED	Sertraline for Alcohol Dependence and Depression
NCT00006180	PHASE4	COMPLETED	Bone Loss in Premenopausal Women With Depression
NCT00006204	PHASE4	COMPLETED	Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine)
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00018759	PHASE4	COMPLETED	Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients
NCT00018824	PHASE4	COMPLETED	Treating Alcohol Use In Older Adults With Depression
NCT00021528	PHASE4	COMPLETED	Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
NCT00029172	PHASE4	COMPLETED	Treatment for Post-Stroke Depression
NCT00030147	PHASE4	COMPLETED	Raloxifene and Rimostil for Perimenopause-Related Depression
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00044616	PHASE4	COMPLETED	Relapse Prevention for Bipolar Type-II Disorder
NCT00045916	PHASE4	COMPLETED	Optimizing Electroconvulsive Therapy for Depression
NCT00047671	PHASE4	COMPLETED	Ethnic Variations in Antidepressant Response
NCT00055328	PHASE4	COMPLETED	Treatment for Depression in the Primary Care Setting
NCT00057551	PHASE4	COMPLETED	Research Evaluating the Value of Augmenting Medication With Psychotherapy
NCT00057577	PHASE4	COMPLETED	Prevention of Recurrence in Depression With Drugs and CT
NCT00067912	PHASE4	COMPLETED	Duloxetine vs. Active Comparator for the Treatment of Depression
NCT00071695	PHASE4	COMPLETED	Duloxetine vs. Active Comparator in the Treatment of Patients With Depression
NCT00073697	PHASE4	COMPLETED	Treatment of Depression in Adults
NCT00106197	PHASE4	UNKNOWN	Hormone and Sleep Response to Antidepressant Treatment in Adolescents and Adults With Depression
NCT00108563	PHASE4	COMPLETED	VISN 20: Prophylactic Treatment of Interferon-Induced Depression in Hepatitis C Patients
NCT00118430	PHASE4	COMPLETED	Stepped Care for Depression and Musculoskeletal Pain
NCT00130455	PHASE4	TERMINATED	Treatment of Depression in the Elderly
NCT00140257	PHASE4	UNKNOWN	DECARD: Study of Escitalopram in the Prevention of Depression in Patients With Acute Coronary Syndrome
NCT00145132	PHASE4	COMPLETED	Beta-CIT-SPECT and Neurophysiology in Depression
NCT00146237	PHASE4	COMPLETED	Phenytoin as an Augmentation for SSRI Failures
NCT00151294	PHASE4	TERMINATED	The Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00152776	PHASE4	COMPLETED	Treating Climacteric Symptoms With a Complex Homeopathic Remedy
NCT00159809	PHASE4	COMPLETED	Efficacy Study Measuring The Impact Of Treatment With Viagra On The Depressive Symptoms Of Men With Erectile Dysfunction
NCT00159965	PHASE4	COMPLETED	Treatments for Psychogenic Nonepileptic Seizures (NES)
NCT00162916	PHASE4	UNKNOWN	Antidepressant Maintenance in Traumatic Brain Injury
NCT00177294	PHASE4	COMPLETED	Augmenting Antidepressant Treatment With Interpersonal Psychotherapy for Treating Late-life Depression
NCT00177424	PHASE4	TERMINATED	Sertraline for Preventing Post-stroke Depression and Improving Rehabilitation Outcomes
NCT00177528	PHASE4	COMPLETED	Safety and Efficacy of Venlafaxine XR in Elderly Patients With Major Depression
NCT00177671	PHASE4	COMPLETED	Antidepressant Medication Plus Donepezil for Treating Late-life Depression
NCT00178035	PHASE4	COMPLETED	Sleep Deprivation Plus Paroxetine for Treating Major Depression in Elderly Individuals
NCT00178048	PHASE4	COMPLETED	Paroxetine in the Treatment of Chronic Primary Insomnia
NCT00178828	PHASE4	COMPLETED	Dynamic Measures of Neurochemistry in Mood Disorders
NCT00181896	PHASE4	TERMINATED	Bupropion SR for Major Depression and Depression NOS in Children and Adolescents With Bipolar Disorder