SH2D6

protein-coding

SH2 domain containing 6, the group of SH2 domain containing

Gene summary

Predicted to enable protein-macromolecule adaptor activity. Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway and intracellular signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001394463.1

Inheritance

—

ClinVar variants

U:19B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr2:85,418,714-85,437,029

External References & Databases

Ensembl (ENSG00000152292)

Transcript & Mutation Effects

hg38 • Region Span ~18.3 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 SH2D6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 25

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394463.1. 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			1
missense			18 clinvar	3 clinvar		21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	19	3	0	22

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394463.1	RefSeq	NP_001381392.1	16	MANE Select
ENST00000469800.7	Ensembl	ENSP00000510308.1	16	MANE Select
ENST00000389938.7	Ensembl	ENSP00000374588.3	9	Standard
ENST00000477170.5	Ensembl	ENSP00000498541.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

transmembrane receptor protein tyrosine kinase signaling pathway
positive regulation of signal transduction
intracellular signal transduction

Molecular Function

SH3/SH2 adaptor activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340326
Coding exons: 4
Length: 18309
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125734
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.467	91	104	0.871	0.00000663	1083
Missense (PolyPhen)		27	32.086	0.84148		352
Synonymous	0.769	37	43.4	0.852	0.00000262	387
Loss of Function	0.229	7	7.69	0.911	4.10e-7	83

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.519
RVIS EVS: 0.46
RVIS percentile EVS: 78.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0173

Gene Damage Prediction

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