SHC1
SHC adaptor protein 1, the group of SH2 domain containing
Basic information
Region (hg38): 1:154962298-154974395
Previous symbols: [ "SHC" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHC1 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 | 0 | |||||
| missense | 32 | 33 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 32 | 1 | 0 |
Variants in SHC1
This is a list of pathogenic ClinVar variants found in the SHC1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-154963870-T-C | not specified | Uncertain significance (Oct 19, 2024) | ||
| 1-154963928-G-A | not specified | Uncertain significance (Jan 17, 2025) | ||
| 1-154965652-T-C | not specified | Uncertain significance (Jun 23, 2023) | ||
| 1-154965680-G-A | not specified | Uncertain significance (Feb 21, 2024) | ||
| 1-154965768-A-T | not specified | Uncertain significance (Mar 07, 2023) | ||
| 1-154965973-T-G | not specified | Uncertain significance (Nov 26, 2024) | ||
| 1-154965978-T-C | not specified | Uncertain significance (Sep 03, 2024) | ||
| 1-154965996-G-C | not specified | Uncertain significance (Aug 10, 2024) | ||
| 1-154966021-G-A | not specified | Uncertain significance (Jul 09, 2024) | ||
| 1-154966026-T-G | not specified | Uncertain significance (Dec 18, 2023) | ||
| 1-154966166-A-C | not specified | Uncertain significance (May 29, 2024) | ||
| 1-154966170-G-T | not specified | Uncertain significance (Mar 31, 2024) | ||
| 1-154966341-G-C | not specified | Uncertain significance (Sep 21, 2023) | ||
| 1-154966383-G-A | not specified | Uncertain significance (Oct 27, 2022) | ||
| 1-154966414-C-T | not specified | Uncertain significance (Oct 16, 2023) | ||
| 1-154966416-C-G | not specified | Uncertain significance (Oct 12, 2024) | ||
| 1-154966417-C-T | not specified | Uncertain significance (Feb 28, 2024) | ||
| 1-154967713-T-C | not specified | Uncertain significance (Feb 08, 2025) | ||
| 1-154968524-G-A | not specified | Uncertain significance (Mar 29, 2023) | ||
| 1-154968530-T-C | not specified | Uncertain significance (Nov 17, 2023) | ||
| 1-154968551-T-C | not specified | Uncertain significance (May 30, 2024) | ||
| 1-154968577-C-T | not specified | Uncertain significance (May 29, 2024) | ||
| 1-154968601-G-A | not specified | Uncertain significance (Apr 24, 2024) | ||
| 1-154968605-G-A | not specified | Uncertain significance (Jan 29, 2025) | ||
| 1-154968802-G-A | not specified | Uncertain significance (Aug 17, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SHC1 | protein_coding | protein_coding | ENST00000448116 | 12 | 12098 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00174 | 0.997 | 125721 | 0 | 25 | 125746 | 0.0000994 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.33 | 289 | 360 | 0.803 | 0.0000204 | 3772 |
| Missense in Polyphen | 57 | 101.98 | 0.55895 | 1162 | ||
| Synonymous | -0.373 | 148 | 142 | 1.04 | 0.00000792 | 1236 |
| Loss of Function | 2.87 | 9 | 24.2 | 0.371 | 0.00000119 | 277 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000307 | 0.000301 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000164 | 0.000163 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.000115 | 0.000114 |
| Middle Eastern | 0.000164 | 0.000163 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. {ECO:0000250, ECO:0000269|PubMed:14665640}.;
- 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);MicroRNAs in cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Insulin Signalling;EGF-Core;IL-5 Signaling Pathway;Angiogenesis overview;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Prolactin Signaling Pathway;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Alpha 6 Beta 4 signaling pathway;JAK-STAT;IL-3 Signaling Pathway;nerve growth factor pathway (ngf);Kit receptor signaling pathway;Focal Adhesion;XBP1(S) activates chaperone genes;IL-6 signaling pathway;TGF-beta Signaling Pathway;Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;BDNF-TrkB Signaling;Association Between Physico-Chemical Features and Toxicity Associated Pathways;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;PDGFR-beta pathway;p38 MAPK Signaling Pathway;Ras Signaling;EMT transition in Colorectal Cancer;EGF-EGFR Signaling Pathway;Insulin Signaling;IL-2 Signaling Pathway;EPO Receptor Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;DNA Damage Response (only ATM dependent);SHC1 events in ERBB2 signaling;Developmental Biology;Signaling by GPCR;Signaling by FGFR2;RAGE;SHC-mediated cascade:FGFR2;Downstream signaling of activated FGFR2;SHC-mediated cascade:FGFR3;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Downstream signaling of activated FGFR3;Disease;Signaling by FGFR3;Signal Transduction;SHC-mediated cascade:FGFR4;Downstream signaling of activated FGFR4;Signaling by Interleukins;DAP12 signaling;DAP12 interactions;Signaling by FGFR4;Signaling by FGFR;bioactive peptide induced signaling pathway;role of erk5 in neuronal survival pathway;links between pyk2 and map kinases;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;egf signaling pathway;il 2 signaling pathway;trefoil factors initiate mucosal healing;transcription factor creb and its extracellular signals;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;integrin signaling pathway;il-2 receptor beta chain in t cell activation;phospholipids as signalling intermediaries;il 4 signaling pathway;multiple antiapoptotic pathways from igf-1r signaling lead to bad phosphorylation;pten dependent cell cycle arrest and apoptosis;vegf hypoxia and angiogenesis;mcalpain and friends in cell motility;nfat and hypertrophy of the heart ;il 6 signaling pathway;sprouty regulation of tyrosine kinase signals;phosphorylation of mek1 by cdk5/p35 down regulates the map kinase pathway;trka receptor signaling pathway;insulin signaling pathway;t cell receptor signaling pathway;bcr signaling pathway;calcium signaling by hbx of hepatitis b virus;erk1/erk2 mapk signaling pathway;role of erbb2 in signal transduction and oncology;keratinocyte differentiation;Cytokine Signaling in Immune system;map kinase inactivation of smrt corepressor;Alpha6Beta4Integrin;Signal attenuation;Insulin receptor signalling cascade;Signaling by Insulin receptor;Signaling by the B Cell Receptor (BCR);SHC1 events in EGFR signaling;igf-1 signaling pathway;Integrin alphaIIb beta3 signaling;il 3 signaling pathway;HGF;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Oncostatin_M;IGF signaling;Innate Immune System;Immune System;Interleukin-15 signaling;Interleukin receptor SHC signaling;Interleukin-2 family signaling;Adaptive Immune System;KitReceptor;Fibroblast growth factor-1;insulin Mam;BCR;ErbB4 signaling events;pdgf signaling pathway;Signaling by EGFR;epo signaling pathway;Platelet Aggregation (Plug Formation);IL-5 signaling;Signalling to RAS;Platelet activation, signaling and aggregation;tpo signaling pathway;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;fc epsilon receptor i signaling in mast cells;Activated NTRK2 signals through RAS;Signaling by NTRK2 (TRKB);Signaling by NTRKs;BDNF;EGFR1;SHP2 signaling;Tie2 Signaling;Integrin signaling;growth hormone signaling pathway;Cell surface interactions at the vascular wall;Hemostasis;the igf-1 receptor and longevity;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;BCR signaling pathway;Signaling events mediated by TCPTP;PDGF;IL2;VEGFR3 signaling in lymphatic endothelium;NGF;Signaling events regulated by Ret tyrosine kinase;IL3;a6b1 and a6b4 Integrin signaling;IL2-mediated signaling events;Gastrin;Signaling by EGFRvIII in Cancer;Signaling by EGFR in Cancer;Angiopoietin receptor Tie2-mediated signaling;EGFR-dependent Endothelin signaling events;Interleukin-2 signaling;IL4;EPO signaling pathway;RET signaling;Axon guidance;IL5;Leptin;Signaling by ERBB2;SHC1 events in ERBB4 signaling;Signaling by ERBB4;IL6;SHC-related events triggered by IGF1R;IGF1R signaling cascade;IL-7;MET activates RAS signaling;Signaling by MET;Constitutive Signaling by EGFRvIII;Signaling by Receptor Tyrosine Kinases;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Signaling by Ligand-Responsive EGFR Variants in Cancer;EGF;ErbB2/ErbB3 signaling events;GMCSF-mediated signaling events;IL2 signaling events mediated by STAT5;Insulin Pathway;Neurotrophic factor-mediated Trk receptor signaling;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;Internalization of ErbB1;IL2 signaling events mediated by PI3K;TCR signaling in naïve CD8+ T cells;p75(NTR)-mediated signaling;EPHB forward signaling;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);Plasma membrane estrogen receptor signaling;Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;IL4-mediated signaling events;Signaling events mediated by PTP1B;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);EPHA2 forward signaling;FGF signaling pathway;TCR signaling in naïve CD4+ T cells;PDGFR-alpha signaling pathway;IL3-mediated signaling events;TGF-beta receptor signaling;Role of LAT2/NTAL/LAB on calcium mobilization;SHC-mediated cascade:FGFR1;insulin;Signaling by FGFR1;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.830
Intolerance Scores
- loftool
- 0.557
- rvis_EVS
- -0.18
- rvis_percentile_EVS
- 40.36
Haploinsufficiency Scores
- pHI
- 0.706
- hipred
- Y
- hipred_score
- 0.792
- ghis
- 0.571
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Shc1
- Phenotype
- cellular phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); embryo phenotype; immune system 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); neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- shc1
- Affected structure
- dorsal longitudinal anastomotic vessel
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- MAPK cascade;activation of MAPK activity;angiogenesis;epidermal growth factor receptor signaling pathway;regulation of epidermal growth factor-activated receptor activity;Ras protein signal transduction;axon guidance;heart development;positive regulation of cell population proliferation;insulin receptor signaling pathway;viral process;cytokine-mediated signaling pathway;actin cytoskeleton reorganization;interleukin-15-mediated signaling pathway;IRE1-mediated unfolded protein response;Fc-epsilon receptor signaling pathway;interleukin-2-mediated signaling pathway;ERBB2 signaling pathway;regulation of growth;defense response to bacterium;negative regulation of apoptotic process;positive regulation of MAPK cascade;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of Ras protein signal transduction;leukocyte migration;positive regulation of ERK1 and ERK2 cascade;cellular response to growth factor stimulus;cell-cell adhesion
- Cellular component
- mitochondrial matrix;cytosol;plasma membrane;Shc-EGFR complex
- Molecular function
- phosphotyrosine residue binding;transmembrane receptor protein tyrosine kinase adaptor activity;Ras guanyl-nucleotide exchange factor activity;epidermal growth factor receptor binding;insulin receptor binding;insulin-like growth factor receptor binding;neurotrophin TRKA receptor binding;protein binding;phospholipid binding;receptor tyrosine kinase binding;ephrin receptor binding;epidermal growth factor binding