RASGRF1

Ras protein specific guanine nucleotide releasing factor 1, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): 15:78959905-79090780

Previous symbols: [ "GRF1" ]

Links

ENSG00000058335 ∙ NCBI:5923 ∙ OMIM:606600 ∙ HGNC:9875 ∙ Uniprot:Q13972 ∙ 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 RASGRF1 gene.

• not provided (25 variants)
• Inborn genetic diseases (24 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RASGRF1 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				8	9	17
missense			24	1	2	27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	1	2	5
Total	0	0	26	10	13

Variants in RASGRF1

This is a list of pathogenic ClinVar variants found in the RASGRF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-78962169-C-T		not specified	Uncertain significance (Nov 09, 2021)
15-78962172-A-T		not specified	Uncertain significance (Sep 29, 2023)
15-78962181-T-C		not specified	Uncertain significance (Dec 19, 2022)
15-78962183-G-A			Benign (Dec 31, 2019)
15-78980634-T-C			Likely benign (Mar 29, 2018)
15-78980692-G-A		not specified	Uncertain significance (Jul 12, 2022)
15-78985067-C-T			Benign (Dec 31, 2019)
15-78985114-T-C		not specified	Uncertain significance (Feb 23, 2023)
15-78985145-G-A			Benign (Dec 29, 2017)
15-78990220-T-C		not specified	Uncertain significance (Jan 31, 2024)
15-78991760-T-A		not specified	Uncertain significance (Oct 29, 2021)
15-78991786-G-A			Benign (Jun 14, 2018)
15-78998100-T-C		not specified	Uncertain significance (Dec 21, 2022)
15-78998140-C-T			Likely benign (Jun 13, 2018)
15-78998145-C-T		not specified	Uncertain significance (Aug 04, 2023)
15-78998176-C-T			Likely benign (May 03, 2018)
15-78998745-G-A		not specified	Uncertain significance (Dec 21, 2023)
15-78999772-T-G		not specified	Uncertain significance (Nov 03, 2023)
15-78999804-G-A			Likely benign (Feb 02, 2018)
15-78999830-C-T		not specified	Uncertain significance (Feb 27, 2023)
15-78999835-G-A		not specified	Uncertain significance (Mar 07, 2024)
15-78999874-G-C		not specified	Uncertain significance (Jun 16, 2023)
15-79003829-C-T		not specified	Uncertain significance (Aug 14, 2023)
15-79003846-G-A			Benign (Jul 19, 2018)
15-79003850-C-T			Likely benign (Jun 23, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RASGRF1	protein_coding	protein_coding	ENST00000419573	28	130827

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000866	125678	0	70	125748	0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.21	446	776	0.575	0.0000482	8406
Missense in Polyphen		111	259.31	0.42807		2671
Synonymous	0.823	312	331	0.942	0.0000223	2437
Loss of Function	6.58	7	63.6	0.110	0.00000307	743

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000451	0.000440
Middle Eastern	0.00	0.00
South Asian	0.0000365	0.0000327
Other	0.000983	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes the exchange of Ras-bound GDP by GTP. {ECO:0000269|PubMed:11389730}.
• Pathway: Focal adhesion - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);TFs Regulate miRNAs related to cardiac hypertrophy;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Integrated Lung Cancer Pathway;Focal Adhesion;MAPK Signaling Pathway;ATM Signaling Network in Development and Disease;p38 MAPK Signaling Pathway;Ras Signaling;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Regulation of Ras family activation;Signal Transduction;sonic hedgehog receptor ptc1 regulates cell cycle;cdc25 and chk1 regulatory pathway in response to dna damage;regulation of cell cycle progression by plk3;Neuronal System;cell cycle: g2/m checkpoint;Regulation of RAC1 activity;rb tumor suppressor/checkpoint signaling in response to dna damage;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Neurotrophic factor-mediated Trk receptor signaling;CDC42 signaling events (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• loftool: 0.170
• rvis_EVS: -1.41
• rvis_percentile_EVS: 4.14

Haploinsufficiency Scores

• pHI: 0.231
• hipred: Y
• hipred_score: 0.830
• ghis: 0.585

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.746

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rasgrf1
• 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); normal phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: MAPK cascade;signal transduction;small GTPase mediated signal transduction;long-term memory;cell population proliferation;neuron projection development;response to endoplasmic reticulum stress;regulation of Rac protein signal transduction;regulation of Rho protein signal transduction;positive regulation of GTPase activity;regulation of Ras protein signal transduction;positive regulation of Ras protein signal transduction;regulation of synaptic plasticity;regulation of neuronal synaptic plasticity;activation of GTPase activity;regulation of NMDA receptor activity
• Cellular component: cytosol;plasma membrane;growth cone;neuron projection
• Molecular function: guanyl-nucleotide exchange factor activity;Ras guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;glutamate receptor binding