NEUROD2

Summary

NEUROD2 (neuronal differentiation 2, HGNC:7763) is a protein-coding gene on chromosome 17q12, encoding Neurogenic differentiation factor 2 (Q15784). Transcriptional regulator implicated in neuronal determination.

This gene encodes a member of the neuroD family of neurogenic basic helix-loop-helix (bHLH) proteins. Expression of this gene can induce transcription from neuron-specific promoters, such as the GAP-43 promoter, which contain a specific DNA sequence known as an E-box. The product of the human gene can induce neurogenic differentiation in non-neuronal cells in Xenopus embryos, and is thought to play a role in the determination and maintenance of neuronal cell fates.

Source: NCBI Gene 4761 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 72 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 109 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 77
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_006160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7763
Approved symbol	NEUROD2
Name	neuronal differentiation 2
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	NDRF, bHLHa1
Ensembl gene	ENSG00000171532
Ensembl biotype	protein_coding
OMIM	601725
Entrez	4761

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000302584, ENST00000580874, ENST00000907630, ENST00000907631, ENST00000961013

RefSeq mRNA: 1 — MANE Select: NM_006160 NM_006160

CCDS: CCDS11338

Canonical transcript exons

ENST00000302584 — 2 exons

Exon	Start	End
ENSE00001121640	39607728	39607920
ENSE00001201196	39603768	39606604

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 99.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.5306 / max 583.2671, expressed in 111 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165604	5.3625	108
165605	0.1680	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.31	gold quality
ganglionic eminence	UBERON:0004023	97.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.52	gold quality
cerebellar cortex	UBERON:0002129	95.44	gold quality
cerebellar hemisphere	UBERON:0002245	95.44	gold quality
cerebellum	UBERON:0002037	94.27	gold quality
right frontal lobe	UBERON:0002810	87.66	gold quality
cingulate cortex	UBERON:0003027	86.42	gold quality
anterior cingulate cortex	UBERON:0009835	86.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.74	gold quality
paraflocculus	UBERON:0005351	85.49	silver quality
Ammon’s horn	UBERON:0001954	85.40	gold quality
neocortex	UBERON:0001950	85.25	gold quality
prefrontal cortex	UBERON:0000451	85.10	gold quality
frontal cortex	UBERON:0001870	84.91	gold quality
frontal lobe	UBERON:0016525	84.91	gold quality
cerebral cortex	UBERON:0000956	84.66	gold quality
superior frontal gyrus	UBERON:0002661	84.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.90	gold quality
postcentral gyrus	UBERON:0002581	83.55	gold quality
cerebellar vermis	UBERON:0004720	83.12	gold quality
sural nerve	UBERON:0015488	82.71	gold quality
primary visual cortex	UBERON:0002436	82.17	gold quality
Brodmann (1909) area 10	UBERON:0013541	81.75	silver quality
parietal lobe	UBERON:0001872	81.16	gold quality
amygdala	UBERON:0001876	79.74	gold quality
embryo	UBERON:0000922	78.96	gold quality
temporal lobe	UBERON:0001871	78.67	gold quality
entorhinal cortex	UBERON:0002728	78.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	2130.45
E-MTAB-10485	yes	1187.23
E-MTAB-8894	yes	1102.77
E-ANND-3	no	1.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
CDKN2A
GAL	Unknown
GAP43
INS	Activation
ITPR1	Activation
ITPR3	Activation
NEUROD1
NEUROD2
PDYN	Unknown
PKN1
REST	Repression
SCRT1	Activation
ZEB1	Activation

JASPAR motifs

Motif	Name	Family
MA0668.1	NEUROD2	Tal-related

JASPAR matrix evidence (PMIDs): PMID:22445365

Upstream regulators (CollecTRI, top): NEUROD1, NEUROD2, NEUROG1, NEUROG3, TCF3

miRNA regulators (miRDB)

95 targeting NEUROD2, 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-6748-5P	100.00	65.81	1057
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548AG	99.77	69.25	1492

Literature-anchored findings (GeneRIF, showing 10)

• expression during trophoblast invasion (PMID:11900979)
• Lower neuroD2 mRNA levels was found in opiate-dependent individuals in the cortex and hippocampus. (PMID:16607387)
• The results of this study did not provide evidence for an involvement of NEUROD2 polymorphisms in the pathophysiology of alcohol dependence. (PMID:20880594)
• Downregulation of NEUROD2 is associated with neurodevelopmental defects in trisomies 18. (PMID:22752091)
• Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder. (PMID:28470106)
• Study identifies a novel role of NeuroD2 as a tumor suppressor and prognostic biomarker in GBM the levels of which are tightly regulated by p53 and miR-210. (PMID:29226333)
• NEUROD2 variants as a cause of early infantile epileptic encephalopathy. (PMID:30323019)
• Expansion of NEUROD2 phenotypes to include developmental delay without seizures. (PMID:33438828)
• Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons. (PMID:34188164)
• NEUROD2 function is dispensable for human pancreatic beta cell specification. (PMID:37955006)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	neurod2	ENSDARG00000016854
mus_musculus	Neurod2	ENSMUSG00000038255
rattus_norvegicus	Neurod2	ENSRNOG00000028417
drosophila_melanogaster	amos	FBGN0003270
drosophila_melanogaster	ato	FBGN0010433
drosophila_melanogaster	tap	FBGN0015550
caenorhabditis_elegans		WBGENE00003018
caenorhabditis_elegans		WBGENE00003595

Paralogs (15): NEUROG3 (ENSG00000122859), NEUROD4 (ENSG00000123307), BHLHE23 (ENSG00000125533), NEUROD1 (ENSG00000162992), NEUROD6 (ENSG00000164600), ATOH8 (ENSG00000168874), ATOH1 (ENSG00000172238), OLIG3 (ENSG00000177468), NEUROG2 (ENSG00000178403), ATOH7 (ENSG00000179774), BHLHA15 (ENSG00000180535), BHLHE22 (ENSG00000180828), NEUROG1 (ENSG00000181965), OLIG1 (ENSG00000184221), OLIG2 (ENSG00000205927)

Protein

Protein identifiers

Neurogenic differentiation factor 2 — Q15784 (reviewed: Q15784)

Alternative names: Class A basic helix-loop-helix protein 1, NeuroD-related factor

All UniProt accessions (1): Q15784

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator implicated in neuronal determination. Mediates calcium-dependent transcription activation by binding to E box-containing promoter. Critical factor essential for the repression of the genetic program for neuronal differentiation; prevents the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Induces transcription of ZEB1, which in turn represses neuronal differentiation by down-regulating REST expression. Plays a role in the establishment and maturation of thalamocortical connections; involved in the segregation of thalamic afferents into distinct barrel domains within layer VI of the somatosensory cortex. Involved in the development of the cerebellar and hippocampal granular neurons, neurons in the basolateral nucleus of amygdala and the hypothalamic-pituitary axis. Associates with chromatin to the DPYSL3 E box-containing promoter.

Subunit / interactions. Interacts with TCF3, TCF4 and TCF12. Interacts with CDC20. Efficient DNA-binding and transcription activation require dimerization with another bHLH protein.

Subcellular location. Nucleus.

Disease relevance. Developmental and epileptic encephalopathy 72 (DEE72) [MIM:618374] A form of epileptic encephalopathy, a heterogeneous group of severe 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. DEE72 is an autosomal dominant form with variable severity and onset in infancy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal region is necessary for depolarization-induced and calcium-dependent transcription activation.

RefSeq proteins (1): NP_006151* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR016637	TF_bHLH_NeuroD	Family
IPR022575	NeuroD_DUF	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050359	bHLH_transcription_factors	Family

Pfam: PF00010, PF12533

UniProt features (12 total): compositionally biased region 4, sequence conflict 2, sequence variant 2, chain 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15784-F1	60.91	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 394 (showing top): AHRARNT_01, GOBP_HINDBRAIN_DEVELOPMENT, MORF_FLT1, GOBP_METENCEPHALON_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, HNF3ALPHA_Q6, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_ASSOCIATIVE_LEARNING, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03

GO Biological Process (20): behavioral fear response (GO:0001662), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), sensory organ development (GO:0007423), associative learning (GO:0008306), protein ubiquitination (GO:0016567), cerebellar cortex development (GO:0021695), positive regulation of synaptic plasticity (GO:0031915), positive regulation of neuron differentiation (GO:0045666), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of calcium-mediated signaling (GO:0050850), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), axon development (GO:0061564), cellular response to electrical stimulus (GO:0071257), cellular response to calcium ion (GO:0071277), positive regulation of synapse maturation (GO:0090129), negative regulation of synapse maturation (GO:2000297), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154), neuron development (GO:0048666)

GO Molecular Function (9): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), protein heterodimerization activity (GO:0046982), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein dimerization activity (GO:0046983)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
neuron differentiation	2
regulation of transcription by RNA polymerase II	2
synapse maturation	2
regulation of synapse maturation	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
behavioral defense response	1
fear response	1
system development	1
animal organ development	1
learning	1
protein modification by small protein conjugation	1
cerebellum development	1
anatomical structure development	1
regulation of synaptic plasticity	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of DNA-templated transcription	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
neuron projection development	1
response to electrical stimulus	1
cellular response to abiotic stimulus	1
response to calcium ion	1
cellular response to metal ion	1
positive regulation of developmental process	1
positive regulation of cellular component organization	1
negative regulation of developmental process	1
negative regulation of synapse organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
cell development	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEUROD2	P84086	P84086	891
NEUROD2	ANAPC1	Q9H1A4	771
NEUROD2	CDC20	Q12834	770
NEUROD2	MYT1L	Q9UL68	652
NEUROD2	TBR1	Q16650	646
NEUROD2	ASCL1	P50553	640
NEUROD2	PAX6	P26367	616
NEUROD2	CKS1B	P33551	572
NEUROD2	LHX2	P50458	544
NEUROD2	POU3F2	P20265	541
NEUROD2	POU4F1	Q01851	540
NEUROD2	EOMES	O95936	503
NEUROD2	FEZF2	Q8TBJ5	492
NEUROD2	NFIX	Q14938	491
NEUROD2	FOXG1	P55315	484
NEUROD2	SATB2	Q9UPW6	484

IntAct

9 interactions, top by confidence:

A	B	Type	Score
NEUROD2	KRT8	psi-mi:“MI:0915”(physical association)	0.400
TK1	NEUROD2	psi-mi:“MI:0915”(physical association)	0.370
FMR1	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000
ERG	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000
HUNK	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000
UBASH3A	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000
TIAM1	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000
RCAN1	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): NEUROD2 (Affinity Capture-MS), NEUROD2 (Proximity Label-MS), NEUROD2 (Two-hybrid), NEUROD2 (Affinity Capture-Western), NEUROD2 (Reconstituted Complex), NEUROD2 (Two-hybrid), NEUROD2 (Two-hybrid), NEUROD2 (Two-hybrid), NEUROD2 (Two-hybrid), NEUROD2 (Two-hybrid), NEUROD2 (Two-hybrid), NEUROD2 (Two-hybrid)

ESM2 similar proteins: A6NEQ2, A6NJT0, A8MYZ6, B5RHS5, O02754, O02755, O02756, O08934, O35392, O35767, O77728, O88470, P05554, P16443, P17542, P17676, P21272, P22091, P28033, P31260, P31277, P31310, P42582, P49715, P49716, P52952, P53566, P58012, P78415, P79765, P81067, Q00322, Q03484, Q05826, Q15744, Q15784, Q32PF6, Q4VUF1, Q60925, Q62414

Diamond homologs: A8E5T6, B6VQA1, O09029, O09105, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O45489, O57598, O88940, O96004, O96642, P10627, P13903, P46581, P48985, P48986, P48987, P57100, P57101, P57102, P59101, P61295, P61296, P70447, P70562, P70595, P70660, P70661, P79765, P79766, P79782, P79920, P97832, Q08DI0, Q0V9X5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NEUROG1	“up-regulates quantity by expression”	NEUROD2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	87
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2430913	NM_006160.4(NEUROD2):c.388G>A (p.Glu130Lys)	Pathogenic
2585123	NM_006160.4(NEUROD2):c.208T>G (p.Leu70Val)	Pathogenic
4537452	NM_006160.4(NEUROD2):c.790G>T (p.Ala264Ser)	Pathogenic
625140	NM_006160.4(NEUROD2):c.401T>C (p.Met134Thr)	Pathogenic
3773654	NM_006160.4(NEUROD2):c.398G>T (p.Arg133Leu)	Likely pathogenic
3897215	NM_006160.4(NEUROD2):c.386G>A (p.Arg129Gln)	Likely pathogenic
625139	NM_006160.4(NEUROD2):c.388G>C (p.Glu130Gln)	Likely pathogenic
872718	NM_006160.4(NEUROD2):c.389A>C (p.Glu130Ala)	Likely pathogenic

SpliceAI

310 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39606617:C:CT	acceptor_gain	1.0000
17:39606617:C:T	acceptor_gain	1.0000
17:39606624:G:T	acceptor_gain	1.0000
17:39607812:A:AC	donor_gain	1.0000
17:39606619:C:CT	acceptor_gain	0.9900
17:39606620:G:T	acceptor_gain	0.9900
17:39606623:C:CT	acceptor_gain	0.9900
17:39606600:GGTGC:G	acceptor_gain	0.9800
17:39606601:GTGC:G	acceptor_gain	0.9800
17:39606602:TGC:T	acceptor_gain	0.9800
17:39606604:CCTGA:C	acceptor_loss	0.9800
17:39606605:C:CC	acceptor_gain	0.9800
17:39606605:CTGAG:C	acceptor_loss	0.9800
17:39606606:T:G	acceptor_loss	0.9800
17:39606612:C:CT	acceptor_gain	0.9800
17:39607812:ATTT:A	donor_gain	0.9800
17:39607813:T:C	donor_gain	0.9800
17:39607804:T:TA	donor_gain	0.9700
17:39606603:GC:G	acceptor_gain	0.9600
17:39606604:CC:C	acceptor_gain	0.9600
17:39607165:T:TA	donor_gain	0.9600
17:39607331:C:CA	donor_gain	0.9400
17:39607721:AACTT:A	donor_loss	0.9400
17:39607722:ACTTA:A	donor_loss	0.9400
17:39607723:CTTA:C	donor_loss	0.9400
17:39607724:TTACC:T	donor_loss	0.9400
17:39607725:TAC:T	donor_loss	0.9400
17:39607727:C:CA	donor_loss	0.9400
17:39606782:CCCGG:C	donor_gain	0.9200
17:39607159:C:CA	donor_gain	0.9200

AlphaMissense

2455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39605971:A:G	L210P	1.000
17:39605977:A:G	L208P	1.000
17:39605977:A:T	L208Q	1.000
17:39605979:A:C	C207W	1.000
17:39605980:C:T	C207Y	1.000
17:39605981:A:G	C207R	1.000
17:39605983:C:T	G206D	1.000
17:39605984:C:G	G206R	1.000
17:39605986:G:T	A205D	1.000
17:39605987:C:G	A205P	1.000
17:39605989:A:T	V204E	1.000
17:39605990:C:T	V204M	1.000
17:39605992:A:G	L203P	1.000
17:39605992:A:T	L203Q	1.000
17:39605994:A:C	N202K	1.000
17:39605994:A:T	N202K	1.000
17:39606001:G:A	T200I	1.000
17:39606001:G:T	T200N	1.000
17:39606004:G:A	P199L	1.000
17:39606004:G:C	P199R	1.000
17:39606004:G:T	P199H	1.000
17:39606005:G:A	P199S	1.000
17:39606006:C:A	Q198H	1.000
17:39606006:C:G	Q198H	1.000
17:39606010:G:A	S197L	1.000
17:39606010:G:C	S197W	1.000
17:39606011:A:G	S197P	1.000
17:39606013:A:C	L196R	1.000
17:39606013:A:G	L196P	1.000
17:39606013:A:T	L196Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000218806 (17:39608511 C>T), RS1000924974 (17:39608393 T>A), RS1001132716 (17:39604871 C>G), RS1001248621 (17:39605086 C>G), RS1002298424 (17:39606921 G>A), RS1002593724 (17:39606739 C>A,T), RS1003160715 (17:39606403 G>A), RS1003186184 (17:39607840 C>A,T), RS1003987867 (17:39604732 G>A), RS1004212308 (17:39606668 AC>A), RS1004283686 (17:39606721 C>T), RS1004834100 (17:39606627 A>G), RS1005337886 (17:39607521 G>A,T), RS1005693473 (17:39607714 T>C), RS1005731604 (17:39606342 T>C)

Disease associations

OMIM: gene MIM:601725 | disease phenotypes: MIM:618374

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 72	Strong	Autosomal dominant
genetic developmental and epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (2): developmental and epileptic encephalopathy, 72 (MONDO:0032710), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (0):

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000463	Anteverted nares
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000565	Esotropia
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0000826	Precocious puberty
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001302	Pachygyria
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001500	Broad finger
HP:0001508	Failure to thrive
HP:0001537	Umbilical hernia

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000624_15	Ulcerative colitis	3.000000e-08
GCST004601_145	Red blood cell count	2.000000e-14
GCST004630_214	Mean corpuscular hemoglobin	3.000000e-10
GCST006436_11	Triglyceride levels	2.000000e-08
GCST008916_10	Asthma	5.000000e-09
GCST008916_21	Asthma	2.000000e-62
GCST008916_45	Asthma	3.000000e-10
GCST008916_86	Asthma	2.000000e-14
GCST009798_16	Asthma	8.000000e-27
GCST010002_123	Refractive error	1.000000e-24
GCST90002403_358	Red blood cell count	2.000000e-38

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation	2
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
abrine	increases expression	1
bisphenol S	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Fonofos	increases methylation	1
Lead	affects expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Asbestos, Serpentine	increases methylation	1
Asbestos, Crocidolite	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4K3	SEES3-1V human NEUROD2, clone1	Embryonic stem cell	Male
CVCL_A4K4	SEES3-1V human NEUROD2, clone2	Embryonic stem cell	Male
CVCL_A4K5	SEES3-1V human NEUROD2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).