SHC3

SHC adaptor protein 3, the group of SH2 domain containing

Basic information

Region (hg38): 9:89005770-89178818

Links

ENSG00000148082 ∙ NCBI:53358 ∙ OMIM:605263 ∙ HGNC:18181 ∙ Uniprot:Q92529 ∙ 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 SHC3 gene.

• Inborn genetic diseases (20 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHC3 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			19	2		21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	3	0

Variants in SHC3

This is a list of pathogenic ClinVar variants found in the SHC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-89013487-C-T		not specified	Uncertain significance (Dec 13, 2023)
9-89038066-G-A		not specified	Uncertain significance (Jul 12, 2022)
9-89038117-C-T		not specified	Uncertain significance (May 11, 2022)
9-89038160-C-T			Likely benign (Jun 26, 2018)
9-89038221-C-A		not specified	Uncertain significance (Dec 30, 2023)
9-89042041-C-T		not specified	Uncertain significance (May 09, 2023)
9-89042057-C-G		not specified	Uncertain significance (Jan 04, 2022)
9-89042072-C-A			Likely benign (Mar 01, 2024)
9-89042113-C-T		not specified	Uncertain significance (Dec 16, 2021)
9-89046956-C-T		not specified	Uncertain significance (Nov 02, 2023)
9-89046966-C-T		not specified	Uncertain significance (Aug 13, 2021)
9-89046968-G-A		not specified	Uncertain significance (Aug 11, 2022)
9-89046992-A-T		not specified	Uncertain significance (Nov 15, 2023)
9-89052088-C-T		not specified	Uncertain significance (Jun 28, 2022)
9-89075168-T-A		not specified	Uncertain significance (Oct 10, 2023)
9-89112583-T-C		not specified	Uncertain significance (Dec 26, 2023)
9-89178025-C-G		not specified	Uncertain significance (Feb 26, 2024)
9-89178040-C-A		not specified	Uncertain significance (Nov 17, 2023)
9-89178040-C-T		not specified	Uncertain significance (Sep 22, 2023)
9-89178067-C-T		not specified	Uncertain significance (Sep 26, 2022)
9-89178078-C-G		not specified	Uncertain significance (Sep 20, 2023)
9-89178088-T-C		not specified	Uncertain significance (Jun 05, 2023)
9-89178094-C-T		not specified	Likely benign (Apr 10, 2023)
9-89178105-G-C		not specified	Uncertain significance (Dec 16, 2022)
9-89178108-G-A		not specified	Uncertain significance (Feb 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHC3	protein_coding	protein_coding	ENST00000375835	12	165623

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0465	0.953	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	231	299	0.773	0.0000163	3839
Missense in Polyphen		67	115.88	0.57819		1451
Synonymous	0.122	121	123	0.986	0.00000716	1214
Loss of Function	3.26	7	24.3	0.288	0.00000118	304

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000534	0.0000527
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons.
• Pathway: Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;EGF-Core;Integrin-mediated Cell Adhesion;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Focal Adhesion;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;Ras Signaling;Insulin Signaling;Developmental Biology;Signal Transduction;HGF;IGF signaling;insulin Mam;IL-5 signaling;Signalling to RAS;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;Signaling by NTRKs;BDNF;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PDGF;NGF;RET signaling;Axon guidance;Signaling by Receptor Tyrosine Kinases;EGF;Neurotrophic factor-mediated Trk receptor signaling;insulin (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.249
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.47

Haploinsufficiency Scores

• pHI: 0.464
• hipred: Y
• hipred_score: 0.704
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shc3
• 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)

Gene ontology

• Biological process: MAPK cascade;transmembrane receptor protein tyrosine kinase signaling pathway;epidermal growth factor receptor signaling pathway;Ras protein signal transduction;axon guidance;central nervous system development;learning or memory;synaptic transmission, glutamatergic
• Cellular component: cellular_component;cytosol;plasma membrane
• Molecular function: phosphotyrosine residue binding;Ras guanyl-nucleotide exchange factor activity;protein binding;receptor tyrosine kinase binding