SH2D2A

protein-coding

SH2 domain containing 2A, the group of SH2 domain containing

Gene summary

This gene encodes an adaptor protein thought to function in T-cell signal transduction. A related protein in mouse is responsible for the activation of lymphocyte-specific protein-tyrosine kinase and functions in downstream signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

MANE transcript

NM_003975.4

Inheritance

—

ClinVar variants

U:60B:6

Top phenotype

NTRK1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr1:156,806,240-156,816,848

External References & Databases

Ensembl (ENSG00000027869)

Transcript & Mutation Effects

hg38 • Region Span ~10.6 kb

Loading mutation effect viewer...

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 SH2D2A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 5

NTRK1-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003975.4. 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	2 clinvar		3
missense			53 clinvar	4 clinvar		57
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	60	6	0	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003975.4	RefSeq	NP_003966.2	8	MANE Select
ENST00000368199.8	Ensembl	ENSP00000357182.3	8	MANE Select
NM_001161441.2	RefSeq	NP_001154913.1	8	Standard
NM_001161442.2	RefSeq	NP_001154914.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

VEGF signaling pathway - Homo sapiens (human)
VEGFA-VEGFR2 Signaling Pathway
EGF-EGFR Signaling Pathway
Signal Transduction
VEGFA-VEGFR2 Pathway

Biological Process

angiogenesis
signal transduction
cell population proliferation
positive regulation of signal transduction
cell differentiation

Molecular Function

SH3/SH2 adaptor activity
protein binding
SH3 domain binding

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392306
Coding exons: 8
Length: 10620
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125745
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.483	200	220	0.908	0.0000117	2532
Missense (PolyPhen)		50	69.742	0.71693		904
Synonymous	1.04	77	89.6	0.860	0.00000480	825
Loss of Function	1.27	12	17.8	0.675	8.61e-7	194

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00031	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00047	0.00046	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could be a T-cell-specific adapter protein involved in the control of T-cell activation. May play a role in the CD4-p56- LCK-dependent signal transduction pathway. Could also play an important role in normal and pathological angiogenesis. Could be an adapter protein that facilitates and regulates interaction of KDR with effector proteins important to endothelial cell survival and proliferation.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.562
RVIS EVS: 0.53
RVIS percentile EVS: 80.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.350

Gene Damage Prediction

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