SHC3

protein-coding

SHC adaptor protein 3, the group of SH2 domain containing

Gene summary

Enables phosphotyrosine residue binding activity. Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within glutamatergic synaptic transmission and learning or memory. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_016848.6

Inheritance

—

ClinVar variants

U:86B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr9:89,005,771-89,178,818

External References & Databases

Ensembl (ENSG00000148082)

Transcript & Mutation Effects

hg38 • Region Span ~173.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHC3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016848.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar		4
missense			84 clinvar	3 clinvar		87
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	86	6	0	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016848.6	RefSeq	NP_058544.3	12	MANE Select
ENST00000375835.9	Ensembl	ENSP00000364995.4	12	MANE Select
ENST00000375831.1	Ensembl	ENSP00000364991.1	3	Standard
ENST00001055116.1	Ensembl	ENSP00000724933.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

MAPK cascade
transmembrane receptor protein tyrosine kinase signaling pathway
epidermal growth factor receptor signaling pathway
Ras protein signal transduction
axon guidance

Molecular Function

phosphotyrosine residue binding
Ras guanyl-nucleotide exchange factor activity
protein binding
receptor tyrosine kinase binding

Cellular Component

cellular_component
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375835
Coding exons: 12
Length: 165623
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.40	231	299	0.773	0.0000163	3839
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.249
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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