NEUROD2

neuronal differentiation 2, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 17:39603536-39609777

Links

ENSG00000171532 ∙ NCBI:4761 ∙ OMIM:601725 ∙ HGNC:7763 ∙ Uniprot:Q15784 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 72 (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 72 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 72	AD	Neurologic	The condition can include refractory seizures and other neurologic manifestations, and placement of a vagal-nerve stimulator has been reported as benefiting seizure control as well as development	Neurologic	30323019

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEUROD2 gene.

• Developmental and epileptic encephalopathy, 72 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEUROD2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	3	1	5
missense	2	1	40	3		46
nonsense			6			6
start loss						0
frameshift			3			3
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	2	1	54	6	1

Highest pathogenic variant AF is 0.00000659

Variants in NEUROD2

This is a list of pathogenic ClinVar variants found in the NEUROD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-39605456-T-G		Inborn genetic diseases	Uncertain significance (Sep 02, 2024)
17-39605480-C-T			Uncertain significance (Aug 06, 2024)
17-39605481-G-T			Uncertain significance (Mar 20, 2023)
17-39605484-C-A		not specified	Uncertain significance (May 04, 2022)
17-39605491-C-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
17-39605510-G-A			Uncertain significance (May 30, 2024)
17-39605523-CAAG-C		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
17-39605548-C-A			Uncertain significance (Aug 12, 2024)
17-39605587-G-C			Uncertain significance (Dec 07, 2023)
17-39605587-GTGGGC-G			Uncertain significance (Jan 04, 2024)
17-39605602-G-A			Uncertain significance (Nov 06, 2024)
17-39605609-C-G		Inborn genetic diseases	Uncertain significance (Jun 03, 2024)
17-39605614-T-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
17-39605621-TAG-T			Uncertain significance (Jun 22, 2020)
17-39605630-G-C			Uncertain significance (Jul 06, 2023)
17-39605644-T-C		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
17-39605648-C-G			Uncertain significance (Apr 10, 2023)
17-39605660-C-A		Developmental and epileptic encephalopathy, 72	Uncertain significance (Jun 30, 2022)
17-39605683-T-C			Uncertain significance (Nov 16, 2023)
17-39605686-A-C		Developmental and epileptic encephalopathy, 72	Uncertain significance (Apr 14, 2022)
17-39605695-G-T		Developmental and epileptic encephalopathy, 72	Uncertain significance (Sep 09, 2022)
17-39605730-G-C			Uncertain significance (May 12, 2022)
17-39605770-A-T			Uncertain significance (Jul 15, 2022)
17-39605810-C-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
17-39605826-GCCCAGGCCGCCGGCC-G			Uncertain significance (Jan 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEUROD2	protein_coding	protein_coding	ENST00000302584	1	6242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.942	0.0578	123173	0	1	123174	0.00000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.67	96	203	0.473	0.00000932	2393
Missense in Polyphen		23	83.776	0.27454		929
Synonymous	0.0146	95	95.2	0.998	0.00000467	808
Loss of Function	2.78	0	9.01	0.00	3.85e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000101	0.000101
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). {ECO:0000250}.

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.0402
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.25

Haploinsufficiency Scores

• pHI: 0.722
• hipred: Y
• hipred_score: 0.736
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.621

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Neurod2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype

Gene ontology

• Biological process: behavioral fear response;regulation of transcription by RNA polymerase II;nervous system development;associative learning;protein ubiquitination;cerebellar cortex development;positive regulation of synaptic plasticity;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;neuron development;positive regulation of calcium-mediated signaling;positive regulation of DNA-binding transcription factor activity;cellular response to electrical stimulus;cellular response to calcium ion;positive regulation of synapse maturation;negative regulation of nucleic acid-templated transcription;negative regulation of synapse maturation
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein heterodimerization activity;E-box binding