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GeneE
3 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SH2D6
SH2 domain containing 6
Chromosome 2 Β· 2p11.2
NCBI Gene: 284948Ensembl: ENSG00000152292.19HGNC: HGNC:30439UniProt: Q7Z4S9
6PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein-macromolecule adaptor activitycell surface receptor protein tyrosine kinase signaling pathwayintracellular signal transductioncytoplasmGenu valgumGenu varumkeratoconuscerebral atherosclerosis
✦AI Summary

SH2D6 encodes an SH2 domain-containing protein involved in intracellular signal transduction and protein-macromolecule adaptor activity 12. The protein localizes to the cytoplasm and participates in cell surface receptor protein tyrosine kinase signaling pathways [GO Annotations]. SH2D6 exhibits a motif similar to the kinesin-light chain 1 (KLC1)-binding motif of JIP1, suggesting it may function as a cargo protein for kinesin1-dependent cellular transport, a mechanism important for neuronal function 3. Clinically, SH2D6 has emerged as relevant to neurodevelopmental disorders. Microdeletions spanning the 2p11.2 region that include SH2D6, along with ELMOD3 and CAPG, have been identified in autism spectrum disorder (ASD) families, with evidence suggesting that ELMOD3-SH2D6 fusion transcripts may contribute to ASD pathogenesis 12. A homozygous 2p11.2 deletion affecting SH2D6 was associated with ASD, intellectual disability, and hearing impairment, indicating SH2D6 may contribute to this contiguous deletion syndrome phenotype 2. These findings suggest SH2D6 plays a role in neurodevelopmental processes, potentially through signal transduction and intracellular transport mechanisms critical for normal brain development and function.

Sources cited
1
ELMOD3-SH2D6 gene fusion in 2p11.2 microdeletion is implicated in autism spectrum disorder with evidence of chimeric transcript production
PMID: 31800155
2
SH2D6 contains a motif similar to JIP1's KLC1-binding motif, suggesting potential function as a kinesin1 cargo protein
PMID: 30026235
3
Homozygous 2p11.2 deletion affecting SH2D6 (along with ELMOD3 and CAPG) is associated with autism spectrum disorder, intellectual disability, and hearing impairment
PMID: 30284680
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜20
Genu valgumOpen Targets
0.11Weak
Genu varumOpen Targets
0.10Suggestive
keratoconusOpen Targets
0.10Suggestive
cerebral atherosclerosisOpen Targets
0.04Suggestive
Barrett's esophagusOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.02Suggestive
Microscopic hematuriaOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
COVID-19Open Targets
0.01Suggestive
autism spectrum disorderOpen Targets
0.01Suggestive
Hearing impairmentOpen Targets
0.00Suggestive
autismOpen Targets
0.00Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
systemic lupus erythematosusOpen Targets
0.00Suggestive
Intellectual disabilityOpen Targets
0.00Suggestive
sessile serrated polypOpen Targets
0.00Suggestive
Crohn's diseaseOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
thyroid cancer, nonmedullary, 1Open Targets
0.00Suggestive
Uterine CarcinosarcomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar β†—
Related Genes
SHC2Shared pathway100%SHC4Shared pathway100%EFSShared pathway67%SH2B1Shared pathway67%ELMOD3Co-mentioned in literature67%PILRBShared pathway50%
Tissue Expression6 tissues
Liver
100%
Brain
43%
Bone Marrow
38%
Ovary
18%
Lung
18%
Heart
11%
Gene Interaction Network
Click a node to explore
SH2D6SHC2SHC4EFSSH2B1ELMOD3PILRB
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q7Z4S9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.46LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.07 [0.79–1.46]
RankingsWhere SH2D6 stands among ~20K protein-coding genes
  • #18,203of 20,598
    Most Researched6
  • #14,896of 17,882
    Most Constrained (LOEUF)1.46
Genes detectedSH2D6
Sources retrieved3 papers
Response timeβ€”
πŸ“„ Sources
3
1
ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario.
PMID: 31800155
J Cell Mol Med Β· 2020
1.00
2
Characterization of the binding mode of JNK-interacting protein 1 (JIP1) to kinesin-light chain 1 (KLC1).
PMID: 30026235
J Biol Chem Β· 2018
0.67
3
Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology.
PMID: 30284680
J Appl Genet Β· 2019
0.33