SHC2

SHC adaptor protein 2, the group of SH2 domain containing

Basic information

Region (hg38): 19:416589-461033

Links

ENSG00000129946 ∙ NCBI:25759 ∙ OMIM:605217 ∙ HGNC:29869 ∙ Uniprot:P98077 ∙ 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 SHC2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHC2 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				3		3
missense			74	2		76
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	74	5	0

Variants in SHC2

This is a list of pathogenic ClinVar variants found in the SHC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-418938-C-T		not specified	Uncertain significance (Feb 05, 2025)
19-418939-G-A		not specified	Uncertain significance (Apr 06, 2024)
19-418954-G-A		not specified	Uncertain significance (May 09, 2023)
19-418975-C-T		not specified	Uncertain significance (Dec 25, 2024)
19-418978-C-A		not specified	Uncertain significance (Jul 21, 2021)
19-418981-C-T		not specified	Uncertain significance (Jan 23, 2024)
19-418989-T-C		not specified	Uncertain significance (Jan 26, 2023)
19-418998-T-A		not specified	Uncertain significance (Dec 26, 2023)
19-419020-G-T		not specified	Uncertain significance (Nov 17, 2022)
19-419049-G-A		not specified	Uncertain significance (Jul 27, 2024)
19-419053-G-A		not specified	Uncertain significance (Oct 25, 2023)
19-422154-C-T		not specified	Uncertain significance (Jan 17, 2024)
19-422160-C-G		not specified	Uncertain significance (Mar 31, 2024)
19-422163-C-T		not specified	Uncertain significance (Jun 26, 2023)
19-422187-C-T		not specified	Uncertain significance (Aug 27, 2024)
19-422194-C-T		not specified	Uncertain significance (Apr 01, 2024)
19-422222-T-C		not specified	Uncertain significance (Oct 25, 2023)
19-422266-C-A		not specified	Uncertain significance (Jul 27, 2024)
19-422268-T-C		not specified	Uncertain significance (Feb 05, 2025)
19-422274-C-T		not specified	Uncertain significance (Dec 14, 2022)
19-422282-C-T		not specified	Uncertain significance (Sep 01, 2024)
19-422283-G-A		not specified	Uncertain significance (May 28, 2024)
19-422285-C-A		not specified	Uncertain significance (Nov 11, 2024)
19-422333-G-A		not specified	Uncertain significance (Feb 12, 2025)
19-422339-G-T		not specified	Uncertain significance (Mar 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHC2	protein_coding	protein_coding	ENST00000264554	12	44414

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.13e-14	0.0315	124490	0	57	124547	0.000229

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.274	277	290	0.955	0.0000200	3653
Missense in Polyphen		138	157.48	0.87632		1576
Synonymous	-0.203	138	135	1.02	0.0000110	1250
Loss of Function	0.312	22	23.6	0.931	0.00000128	274

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000958	0.000928
Ashkenazi Jewish	0.00	0.00
East Asian	0.000513	0.000501
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000151
Middle Eastern	0.000513	0.000501
South Asian	0.000198	0.000196
Other	0.000167	0.000165

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 (By similarity). {ECO:0000250}.
• Pathway: Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);VEGF 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;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Focal Adhesion;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;Ras Signaling;Insulin Signaling;ErbB Signaling Pathway;Signal Transduction;VEGFA-VEGFR2 Pathway;HGF;IGF signaling;insulin Mam;IL-5 signaling;Signalling to RAS;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;Signaling by NTRKs;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PDGF;NGF;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;EGF;Neurotrophic factor-mediated Trk receptor signaling;VEGFR1 specific signals;insulin (Consensus)

Recessive Scores

• pRec: 0.245

Haploinsufficiency Scores

• pHI: 0.0853
• hipred: Y
• hipred_score: 0.575
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shc2
• 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;activation of MAPK activity;Ras protein signal transduction;vascular endothelial growth factor receptor signaling pathway
• Cellular component: cellular_component;cytosol;plasma membrane
• Molecular function: Ras guanyl-nucleotide exchange factor activity;protein binding;receptor tyrosine kinase binding