SHC4

SHC adaptor protein 4, the group of SH2 domain containing

Basic information

Region (hg38): 15:48823740-48963919

Links

ENSG00000185634 ∙ NCBI:399694 ∙ OMIM:617372 ∙ HGNC:16743 ∙ Uniprot:Q6S5L8 ∙ 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 SHC4 gene.

• Inborn genetic diseases (33 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHC4 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			24	1		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			7	1		8
Total	0	0	31	2	0

Variants in SHC4

This is a list of pathogenic ClinVar variants found in the SHC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-48834946-C-A		not specified	Uncertain significance (Mar 01, 2023)
15-48835003-C-G		not specified	Uncertain significance (Dec 28, 2022)
15-48843498-T-C		not specified	Uncertain significance (Dec 09, 2023)
15-48851194-C-T		not specified	Uncertain significance (Jul 13, 2021)
15-48851220-T-C		not specified	Uncertain significance (Jul 19, 2023)
15-48851226-C-T		not specified	Uncertain significance (Jul 20, 2021)
15-48856002-G-A		not specified	Uncertain significance (Mar 29, 2022)
15-48856094-C-G		not specified	Uncertain significance (Apr 12, 2023)
15-48857762-T-C		not specified	Uncertain significance (Mar 23, 2023)
15-48857805-T-C		not specified	Uncertain significance (May 04, 2023)
15-48867845-C-T		not specified	Uncertain significance (Jul 05, 2023)
15-48878187-T-C		not specified	Uncertain significance (Jun 26, 2023)
15-48878213-G-C		not specified	Uncertain significance (Feb 06, 2024)
15-48878225-C-G		not specified	Uncertain significance (Jan 17, 2024)
15-48878241-T-C		not specified	Uncertain significance (Dec 16, 2022)
15-48878325-A-C		not specified	Likely benign (Oct 03, 2022)
15-48878328-A-G		not specified	Uncertain significance (Oct 25, 2022)
15-48878346-C-G		not specified	Uncertain significance (Oct 06, 2021)
15-48878360-G-A		not specified	Uncertain significance (Nov 09, 2022)
15-48878370-C-T		not specified	Uncertain significance (Mar 01, 2023)
15-48878393-C-T		not specified	Uncertain significance (Jan 23, 2024)
15-48878416-C-A		not specified	Uncertain significance (Nov 01, 2021)
15-48878691-A-G		not specified	Uncertain significance (Feb 22, 2024)
15-48884259-C-T		not specified	Uncertain significance (Feb 28, 2024)
15-48884265-T-A		not specified	Uncertain significance (Jul 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHC4	protein_coding	protein_coding	ENST00000332408	12	139710

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.11e-11	0.866	125661	0	87	125748	0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.123	349	356	0.982	0.0000181	4114
Missense in Polyphen		113	120.7	0.93619		1432
Synonymous	-0.0447	143	142	1.00	0.00000778	1237
Loss of Function	1.81	21	32.1	0.655	0.00000178	355

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000529	0.000529
Ashkenazi Jewish	0.00304	0.00298
East Asian	0.000386	0.000381
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000169	0.000167
Middle Eastern	0.000386	0.000381
South Asian	0.000462	0.000457
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activates both Ras-dependent and Ras-independent migratory pathways in melanomas. Contributes to the early phases of agrin-induced tyrosine phosphorylation of CHRNB1. {ECO:0000269|PubMed:17409413}.
• 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);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Focal Adhesion;Chemokine signaling pathway;Ras Signaling;BDNF (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.766
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.67

Haploinsufficiency Scores

• pHI: 0.299
• hipred: Y
• hipred_score: 0.690
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0629

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shc4

Gene ontology

• Biological process: apoptotic process;positive regulation of cell population proliferation;regulation of gene expression;intracellular signal transduction;stem cell differentiation
• Cellular component: plasma membrane;cell junction;postsynaptic membrane
• Molecular function: protein binding;protein domain specific binding;receptor tyrosine kinase binding