SH2D3A

protein-coding

SH2 domain containing 3A, the group of NSP adaptor proteins|SH2 domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity and phosphotyrosine residue binding activity. Predicted to be involved in JNK cascade. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_005490.3

Inheritance

—

ClinVar variants

U:107B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr19:6,752,160-6,767,463

External References & Databases

Ensembl (ENSG00000125731)

Transcript & Mutation Effects

hg38 • Region Span ~15.3 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 SH2D3A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005490.3. 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			2 clinvar			2
missense			102 clinvar	4 clinvar		106
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	107	4	0	111

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005490.3	RefSeq	NP_005481.2	9	MANE Select
ENST00000245908.11	Ensembl	ENSP00000245908.5	9	MANE Select
NM_001386583.1	RefSeq	NP_001373512.1	8	Standard
NM_001386584.1	RefSeq	NP_001373513.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

JNK cascade
small GTPase mediated signal transduction
positive regulation of signal transduction
positive regulation of peptidyl-serine phosphorylation

Molecular Function

SH3/SH2 adaptor activity
guanyl-nucleotide exchange factor activity
protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000245908
Coding exons: 9
Length: 15429
Individuals with no LoFs: 125486
Homozygous LoFs: 0
Heterozygous LoFs: 262
Defined: 125748
p: 0.00104

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.05	310	366	0.846	0.0000245	3587
Missense (PolyPhen)		103	110.69	0.93051		1224
Synonymous	1.15	141	160	0.884	0.0000103	1293
Loss of Function	1.47	15	22.5	0.667	0.00000130	224

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0024	0.0024	notable
Latino/Admixed American	0.00087	0.00087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0037	0.0036	notable
Finnish	0.00072	0.00046	rare
European (Non-Finnish)	0.00057	0.00056	rare
South Asian	0.0016	0.0016	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in JNK activation.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.554
RVIS EVS: 1.51
RVIS percentile EVS: 95.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.429

Gene Damage Prediction

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