NEUROG3

neurogenin 3, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 10:69571698-69573422

Links

ENSG00000122859 ∙ NCBI:50674 ∙ OMIM:604882 ∙ HGNC:13806 ∙ Uniprot:Q9Y4Z2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• permanent neonatal diabetes mellitus (Strong), mode of inheritance: AR
• congenital malabsorptive diarrhea 4 (Strong), mode of inheritance: AR
• congenital malabsorptive diarrhea 4 (Strong), mode of inheritance: AR
• congenital malabsorptive diarrhea 4 (Strong), mode of inheritance: AR
• congenital malabsorptive diarrhea 4 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diarrhea 4, malabsorptive, congenital	AR	Gastrointestinal	Individuals may present in infancy with severe hyperchloremic metabolic acidosis due to vomiting and diarrhea, and may require parenteral nutrition and limited enteral feeding (with oral vitamins and electrolyte supplementation); Surveillance may allow early recognition and treatment of diabetes mellitus (including with insulin); One reported individual required liver/intestinal transplant	Endocrine; Gastrointestinal	16855267; 21490072

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEUROG3 gene.

• not_provided (123 variants)
• Inborn_genetic_diseases (33 variants)
• Congenital_malabsorptive_diarrhea_4 (15 variants)
• NEUROG3-related_disorder (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEUROG3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020999.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				46	2	48
missense	2	4	80	4	1	91
nonsense	3	1	1			5
start loss						0
frameshift	2	1	3			6
splice donor/acceptor (+/-2bp)						0
Total	7	6	84	50	3

Highest pathogenic variant AF is 0.000012391298

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEUROG3	protein_coding	protein_coding	ENST00000242462	1	1541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000596	0.151	125681	0	32	125713	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.517	143	127	1.13	0.00000595	1325
Missense in Polyphen		39	37.962	1.0273		421
Synonymous	-0.491	64	59.2	1.08	0.00000287	495
Loss of Function	-0.686	7	5.30	1.32	2.46e-7	49

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000413	0.000410
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000447	0.0000440
Middle Eastern	0.000164	0.000163
South Asian	0.000335	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional regulator. Together with NKX2- 2, initiates transcriptional activation of NEUROD1. Involved in neurogenesis. Also required for the specification of a common precursor of the 4 pancreatic endocrine cell types (By similarity). {ECO:0000250}.
• Disease: DISEASE: Diarrhea 4, malabsorptive, congenital (DIAR4) [MIM:610370]: A disease characterized by severe, life-threatening watery diarrhea associated with generalized malabsorption and a paucity of enteroendocrine cells. {ECO:0000269|PubMed:16855267}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Maturity onset diabetes of the young - Homo sapiens (human);Notch-mediated HES/HEY network (Consensus)

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.381
• rvis_EVS: 0.24
• rvis_percentile_EVS: 68.98

Haploinsufficiency Scores

• pHI: 0.0709
• hipred: N
• hipred_score: 0.290
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.283

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Neurog3
• Phenotype: renal/urinary system phenotype; digestive/alimentary phenotype; normal 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; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;nervous system development;central nervous system development;peripheral nervous system development;spinal cord development;epithelial cell differentiation;forebrain development;hindbrain development;endocrine pancreas development;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;regulation of dendrite morphogenesis;positive regulation of DNA-binding transcription factor activity;transdifferentiation
• Cellular component: nucleus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;transcription coactivator activity;protein binding;chromatin DNA binding;protein dimerization activity