GRB10

growth factor receptor bound protein 10, the group of SH2 domain containing|Pleckstrin homology domain containing

Basic information

Region (hg38): 7:50590062-50793462

Links

ENSG00000106070 ∙ NCBI:2887 ∙ OMIM:601523 ∙ HGNC:4564 ∙ Uniprot:Q13322 ∙ 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 GRB10 gene.

• Inborn genetic diseases (19 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRB10 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	2
missense			19	2	2	23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	19	3	4

Variants in GRB10

This is a list of pathogenic ClinVar variants found in the GRB10 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-50593079-G-A		not specified	Likely benign (May 18, 2022)
7-50593090-G-A		GRB10-related disorder	Benign (Oct 22, 2019)
7-50595451-A-T		not specified	Uncertain significance (Nov 17, 2022)
7-50604017-G-C		GRB10-related disorder	Likely benign (Apr 06, 2022)
7-50604057-G-A		GRB10-related disorder	Benign (Aug 01, 2023)
7-50604095-G-A		GRB10-related disorder	Benign (Jun 13, 2019)
7-50604364-C-T		not specified	Uncertain significance (Dec 01, 2022)
7-50605280-G-A		GRB10-related disorder	Likely benign (Aug 28, 2019)
7-50605332-T-T			Benign (Nov 05, 2018)
7-50605333-G-A		not specified	Uncertain significance (Jul 21, 2021)
7-50605335-C-T		GRB10-related disorder	Likely benign (Jun 01, 2023)
7-50605414-G-A		GRB10-related disorder	Likely benign (Nov 13, 2019)
7-50606346-C-T		GRB10-related disorder	Benign (Mar 01, 2019)
7-50612776-T-C		not specified	Uncertain significance (Oct 05, 2022)
7-50614779-G-A		GRB10-related disorder	Likely benign (Feb 28, 2019)
7-50614787-G-A		not specified	Likely benign (Feb 14, 2023)
7-50614835-T-C		not specified	Likely benign (Nov 21, 2023)
7-50616278-A-T		not specified	Uncertain significance (May 08, 2023)
7-50616290-G-C		not specified	Uncertain significance (Mar 22, 2022)
7-50616300-A-G		GRB10-related disorder	Likely benign (Jan 31, 2020)
7-50618118-C-T		not specified	Uncertain significance (Feb 15, 2023)
7-50619200-G-A		GRB10-related disorder	Likely benign (Feb 19, 2019)
7-50626906-G-C		not specified	Uncertain significance (Oct 12, 2021)
7-50626912-T-C		not specified	Uncertain significance (Feb 22, 2023)
7-50669744-G-A			Uncertain significance (Jul 01, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRB10	protein_coding	protein_coding	ENST00000398812	16	203400

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.939	0.0605	124776	0	20	124796	0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.53	255	334	0.764	0.0000207	3916
Missense in Polyphen		33	93.263	0.35384		1077
Synonymous	0.0592	138	139	0.994	0.00000947	1123
Loss of Function	4.57	6	35.3	0.170	0.00000182	387

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000352	0.000352
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000111	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000795	0.0000794
Middle Eastern	0.000111	0.000111
South Asian	0.0000327	0.0000327
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin- stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin- stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2. {ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:16434550, ECO:0000269|PubMed:17376403}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);IGF-Ncore;Kit receptor signaling pathway;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;VEGFA-VEGFR2 Signaling Pathway;Pathways in clear cell renal cell carcinoma;EGF-EGFR Signaling Pathway;Insulin Signaling;Developmental Biology;Signal Transduction;IRS activation;Signal attenuation;Insulin receptor signalling cascade;Signaling by Insulin receptor;EGFR1;Signaling events regulated by Ret tyrosine kinase;RET signaling;Axon guidance;Signaling by SCF-KIT;Signaling by Receptor Tyrosine Kinases;Insulin Pathway;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);PDGFR-beta signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2 (Consensus)

Recessive Scores

• pRec: 0.674

Intolerance Scores

• loftool: 0.197
• rvis_EVS: -0.13
• rvis_percentile_EVS: 43.91

Haploinsufficiency Scores

• pHI: 0.420
• hipred: Y
• hipred_score: 0.759
• ghis: 0.398

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grb10
• 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); embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region 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)

Gene ontology

• Biological process: axon guidance;negative regulation of Wnt signaling pathway;positive regulation of vascular endothelial growth factor receptor signaling pathway;negative regulation of phosphorylation;negative regulation of glucose import;negative regulation of insulin receptor signaling pathway;insulin-like growth factor receptor signaling pathway;positive regulation of cold-induced thermogenesis
• Cellular component: cytoplasm;cytosol;plasma membrane;protein-containing complex
• Molecular function: SH3/SH2 adaptor activity;insulin receptor binding;protein binding