NGEF

neuronal guanine nucleotide exchange factor, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 2:232878700-233013256

Links

ENSG00000066248 ∙ NCBI:25791 ∙ OMIM:605991 ∙ HGNC:7807 ∙ Uniprot:Q8N5V2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (25 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NGEF 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	1
missense			24	1		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	1	1

Variants in NGEF

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

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

Position	Type	Phenotype	Significance	ClinVar
2-232879503-G-A		not specified	Uncertain significance (Jul 19, 2022)
2-232879512-G-T		not specified	Uncertain significance (Jul 25, 2023)
2-232879560-G-A		not specified	Uncertain significance (Feb 21, 2024)
2-232879565-C-T		not specified	Uncertain significance (Sep 20, 2023)
2-232879643-C-T		not specified	Uncertain significance (Oct 13, 2023)
2-232879665-C-T		not specified	Uncertain significance (Aug 28, 2023)
2-232879674-T-G		not specified	Uncertain significance (Jul 26, 2021)
2-232881149-C-T		not specified	Uncertain significance (Oct 29, 2021)
2-232881151-T-A		not specified	Uncertain significance (Jul 13, 2021)
2-232883437-G-A		not specified	Uncertain significance (Aug 01, 2022)
2-232884085-C-T		not specified	Uncertain significance (Apr 22, 2022)
2-232885302-T-C		not specified	Uncertain significance (Dec 20, 2023)
2-232885341-C-T		not specified	Uncertain significance (Mar 17, 2023)
2-232888041-G-C		not specified	Uncertain significance (Jan 16, 2024)
2-232888068-A-G		not specified	Uncertain significance (Apr 13, 2023)
2-232891371-T-C		not specified	Uncertain significance (Dec 01, 2022)
2-232891455-G-A		not specified	Uncertain significance (May 31, 2022)
2-232891456-C-T		not specified	Uncertain significance (Jan 10, 2023)
2-232891467-C-G		not specified	Uncertain significance (Aug 28, 2023)
2-232891481-C-T			Benign (Jun 14, 2018)
2-232892941-C-T		not specified	Uncertain significance (Sep 01, 2021)
2-232892986-C-T		not specified	Uncertain significance (Feb 22, 2023)
2-232894855-G-A		not specified	Uncertain significance (Dec 01, 2022)
2-232920493-C-T		not specified	Uncertain significance (May 18, 2023)
2-232920507-T-G		not specified	Uncertain significance (Sep 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NGEF	protein_coding	protein_coding	ENST00000264051	14	134587

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.660	0.340	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	335	432	0.775	0.0000270	4687
Missense in Polyphen		107	178.83	0.59832		1821
Synonymous	-0.00816	181	181	1.00	0.0000120	1343
Loss of Function	4.31	7	34.2	0.205	0.00000153	402

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000444	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role in axon guidance regulating ephrin-induced growth cone collapse and dendritic spine morphogenesis. Upon activation by ephrin through EPHA4, the GEF activity switches toward RHOA resulting in its activation. Activated RHOA promotes cone retraction at the expense of RAC1- and CDC42-stimulated growth cone extension (By similarity). {ECO:0000250}.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Signaling by GPCR;Signal Transduction;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Axon guidance;G alpha (12/13) signalling events;GPCR downstream signalling;Regulation of CDC42 activity;Cell death signalling via NRAGE, NRIF and NADE;EPHA forward signaling;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.462
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.82

Haploinsufficiency Scores

• pHI: 0.301
• hipred: Y
• hipred_score: 0.795
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.850

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ngef
• 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); cellular phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;regulation of Rho protein signal transduction;positive regulation of apoptotic process;regulation of GTPase activity;ephrin receptor signaling pathway;regulation of small GTPase mediated signal transduction;negative regulation of dendritic spine morphogenesis
• Cellular component: cytosol;membrane;growth cone
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity