NEUROD1

neuronal differentiation 1, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 2:181668295-181680827

Previous symbols: [ "NEUROD" ]

Links

ENSG00000162992 ∙ NCBI:4760 ∙ OMIM:601724 ∙ HGNC:7762 ∙ Uniprot:Q13562 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Limited), mode of inheritance: AR
• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Strong), mode of inheritance: AR
• maturity-onset diabetes of the young type 6 (Strong), mode of inheritance: AR
• maturity-onset diabetes of the young (Supportive), mode of inheritance: AD
• maturity-onset diabetes of the young type 6 (Strong), mode of inheritance: AD
• monogenic diabetes (Limited), mode of inheritance: AD
• monogenic diabetes (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Maturity onset diabetes of the young 6	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	10545951

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEUROD1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEUROD1 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	63		64
missense		1	140	2	1	144
nonsense			4			4
start loss						0
frameshift			1			1
inframe indel			5			5
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			25	7	4	36
Total	0	1	176	72	5

Variants in NEUROD1

This is a list of pathogenic ClinVar variants found in the NEUROD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-181676189-G-T		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181676195-C-T		Maturity-onset diabetes of the young type 6	Benign (Jan 12, 2018)
2-181676207-A-G		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181676235-G-A		Maturity-onset diabetes of the young type 6	Likely benign (Jan 12, 2018)
2-181676304-T-C		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 12, 2018)
2-181676451-A-G		Maturity-onset diabetes of the young type 6	Benign (Jan 13, 2018)
2-181676665-A-C		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 15, 2018)
2-181676694-A-G		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181676757-A-C		Maturity-onset diabetes of the young type 6	Benign (Jan 13, 2018)
2-181676883-A-G		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181676931-G-T		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 12, 2018)
2-181676971-G-C		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181676995-A-G		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181677017-T-G		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181677071-C-T		Maturity-onset diabetes of the young type 6	Likely benign (Jan 12, 2018)
2-181677072-G-A		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 12, 2018)
2-181677112-A-AT		Maturity onset diabetes mellitus in young	Uncertain significance (Jun 14, 2016)
2-181677112-A-ATT		Maturity onset diabetes mellitus in young	Uncertain significance (Jun 14, 2016)
2-181677112-A-ATTTT		Maturity onset diabetes mellitus in young	Uncertain significance (Jun 14, 2016)
2-181677146-TAC-T		Maturity onset diabetes mellitus in young	Uncertain significance (Jun 14, 2016)
2-181677148-C-CAA		Maturity onset diabetes mellitus in young	Uncertain significance (Jun 14, 2016)
2-181677173-G-A		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181677182-A-G		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181677242-A-T		Maturity-onset diabetes of the young type 6	Uncertain significance (Jan 13, 2018)
2-181677326-TA-T		Maturity onset diabetes mellitus in young	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEUROD1	protein_coding	protein_coding	ENST00000295108	1	7789

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.771	0.227	125746	1	1	125748	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.233	191	200	0.954	0.0000104	2362
Missense in Polyphen		45	59.139	0.76091		706
Synonymous	-1.65	101	82.0	1.23	0.00000463	704
Loss of Function	2.51	1	9.23	0.108	3.97e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000163	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis (By similarity). {ECO:0000250}.
• Disease: DISEASE: Maturity-onset diabetes of the young 6 (MODY6) [MIM:606394]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10545951, ECO:0000269|PubMed:11719843, ECO:0000269|PubMed:26773576}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10545951}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Maturity onset diabetes of the young - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Dopaminergic Neurogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

• pRec: 0.737

Intolerance Scores

• loftool: 0.171
• rvis_EVS: -0.12
• rvis_percentile_EVS: 45.13

Haploinsufficiency Scores

• pHI: 0.978
• hipred: Y
• hipred_score: 0.766
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.862

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Neurod1
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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); renal/urinary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; 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); homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: neurod1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: pancreatic A cell fate commitment;pancreatic PP cell fate commitment;nucleocytoplasmic transport;nitric oxide mediated signal transduction;response to glucose;anterior/posterior pattern specification;dentate gyrus development;cerebellum development;neurogenesis;signal transduction involved in regulation of gene expression;insulin secretion;endocrine pancreas development;amacrine cell differentiation;enteroendocrine cell differentiation;response to drug;glucose homeostasis;positive regulation of apoptotic process;positive regulation of cell differentiation;positive regulation of neuron differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of JAK-STAT cascade;embryonic organ morphogenesis;neuron development;inner ear development;regulation of insulin secretion;positive regulation of DNA-binding transcription factor activity;regulation of intestinal epithelial structure maintenance;regulation of cell cycle arrest;cellular response to glucose stimulus;negative regulation of type B pancreatic cell apoptotic process;positive regulation of transcription regulatory region DNA binding
• Cellular component: nucleus;nucleoplasm;cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;transcription factor binding;sequence-specific DNA binding;protein heterodimerization activity;E-box binding