SH2D6

Summary

SH2D6 (SH2 domain containing 6, HGNC:30439) is a protein-coding gene on chromosome 2p11.2, encoding SH2 domain-containing protein 6 (Q7Z4S9).

Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway and intracellular signal transduction. Predicted to be active in cytoplasm.

Source: NCBI Gene 284948 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_001394463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30439
Approved symbol	SH2D6
Name	SH2 domain containing 6
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35993, SLNK
Ensembl gene	ENSG00000152292
Ensembl biotype	protein_coding
Entrez	284948

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding

ENST00000340326, ENST00000389938, ENST00000469800, ENST00000477170, ENST00000481395, ENST00000481426, ENST00000488219, ENST00000488657, ENST00000651736, ENST00000651962, ENST00000965156

RefSeq mRNA: 1 — MANE Select: NM_001394463 NM_001394463

CCDS: CCDS92791

Canonical transcript exons

ENST00000469800 — 24 exons

Exon	Start	End
ENSE00001324969	85434473	85434497
ENSE00001516690	85429981	85430015
ENSE00001516695	85428584	85428697
ENSE00001516697	85425308	85425407
ENSE00001858242	85418714	85418930
ENSE00001940155	85436837	85437029
ENSE00003556696	85434340	85434370
ENSE00003587163	85435666	85435824
ENSE00003650687	85435065	85435123
ENSE00003841648	85433099	85433121
ENSE00003842090	85430364	85430434
ENSE00003842198	85430538	85430652
ENSE00003842338	85435413	85435496
ENSE00003843220	85431210	85431268
ENSE00003844354	85429372	85429468
ENSE00003846277	85429587	85429612
ENSE00003846478	85433571	85433631
ENSE00003847990	85434033	85434111
ENSE00003849046	85431899	85431959
ENSE00003924772	85436466	85436594
ENSE00004472111	85422596	85422690
ENSE00004475317	85422203	85422314
ENSE00004475329	85422430	85422490
ENSE00004475430	85419029	85419244

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 94.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0686 / max 8.8601, expressed in 30 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21210	0.0686	30

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	94.29	gold quality
pancreatic ductal cell	CL:0002079	83.31	gold quality
right testis	UBERON:0004534	81.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.76	gold quality
left testis	UBERON:0004533	80.21	gold quality
transverse colon	UBERON:0001157	78.12	gold quality
testis	UBERON:0000473	76.63	gold quality
right lobe of thyroid gland	UBERON:0001119	76.14	gold quality
left lobe of thyroid gland	UBERON:0001120	75.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.81	gold quality
body of pancreas	UBERON:0001150	75.30	gold quality
thyroid gland	UBERON:0002046	74.03	gold quality
small intestine	UBERON:0002108	73.36	gold quality
duodenum	UBERON:0002114	72.07	gold quality
epithelial cell of pancreas	CL:0000083	70.17	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	69.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.03	gold quality
ileal mucosa	UBERON:0000331	67.63	silver quality
tibialis anterior	UBERON:0001385	67.57	silver quality
cerebellar hemisphere	UBERON:0002245	67.50	gold quality
cerebellar cortex	UBERON:0002129	67.40	gold quality
spinal cord	UBERON:0002240	67.14	gold quality
right lobe of liver	UBERON:0001114	66.97	gold quality
cartilage tissue	UBERON:0002418	66.70	gold quality
cerebellum	UBERON:0002037	66.49	gold quality
biceps brachii	UBERON:0001507	66.06	gold quality
intestine	UBERON:0000160	66.05	gold quality
colonic epithelium	UBERON:0000397	65.56	gold quality
substantia nigra	UBERON:0002038	65.01	gold quality
colon	UBERON:0001155	64.99	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	3939.35
E-MTAB-8495	yes	3320.54
E-CURD-88	yes	3039.42
E-CURD-122	yes	2675.25
E-MTAB-9906	yes	2485.82
E-GEOD-125970	yes	958.18
E-ANND-3	yes	7.55
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario. (PMID:31800155)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sh2d6	ENSMUSG00000052631
rattus_norvegicus	Sh2d6	ENSRNOG00000013605

Paralogs (3): LCP2 (ENSG00000043462), BLNK (ENSG00000095585), CLNK (ENSG00000109684)

Protein

Protein identifiers

SH2 domain-containing protein 6 — Q7Z4S9 (reviewed: Q7Z4S9)

All UniProt accessions (6): Q7Z4S9, A0A494C0C6, A0A494C0E1, A0A494C0G9, A0A494C0H5, A0A494C1I8

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z4S9-3	3	yes
Q7Z4S9-4	4

RefSeq proteins (1): NP_001381392* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051751	Immunoreceptor_sig_adapters	Family

Pfam: PF00017

UniProt features (11 total): compositionally biased region 4, region of interest 2, splice variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4S9-F1	63.52	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, AACWWCAANK_UNKNOWN, ELK1_01, chr2p11, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, TCANNTGAY_SREBP1_01, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY, ATF6_TARGET_GENES, CBX7_TARGET_GENES, CREB3L4_TARGET_GENES, DLX6_TARGET_GENES, FEV_TARGET_GENES, FOXN3_TARGET_GENES

GO Biological Process (2): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), intracellular signal transduction (GO:0035556)

GO Molecular Function (0):

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
enzyme-linked receptor protein signaling pathway	1
signal transduction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH2D6	ELMOD3	Q96FG2	695
SH2D6	C2orf68	Q2NKX9	480
SH2D6	TMEM150A	Q86TG1	404
SH2D6	CYSTM1	Q9H1C7	382
SH2D6	SHF	Q7M4L6	376
SH2D6	SH2D1B	O14796	366
SH2D6	SHD	Q96IW2	359
SH2D6	RNF181	Q9P0P0	353
SH2D6	SNAP29	O95721	347
SH2D6	SLC25A1	P53007	342
SH2D6	KCTD16	Q68DU8	323
SH2D6	STAP1	Q9ULZ2	316
SH2D6	SH2D1A	O60880	297
SH2D6	IMMP2L	Q96T52	284
SH2D6	KLC1	Q07866	284

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2AIP0, A2RRU4, A2RRW4, A4Q9F4, A6QM06, A6QNS9, A6QPC0, A8MTA8, E1BBQ2, F1LQY6, G3X6E2, H3BNL1, O70373, P29590, P50747, P55199, P97260, Q04841, Q12770, Q2TBR5, Q4QR77, Q5E9N3, Q5MNU5, Q5RDC3, Q69Z89, Q6GQT6, Q6J272, Q702N8, Q70EL4, Q7Z4S9, Q8BL74, Q8BUM9, Q8C419, Q8IVA1, Q8IW40, Q8N1F8, Q8N9H8, Q8WUA4, Q91ZP9, Q920N2

Diamond homologs: O55033, P08487, P10686, P19174, Q13094, Q4KM52, Q60787, Q62077, Q7Z4S9, Q7Z7G1, Q9D413, Q9QUN3, Q9QZE2, Q9YGC1, P24604, P42680, P97504, Q8WV28, P16885

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

37 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

659 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85434922:G:GT	donor_gain	0.9900
2:85435822:G:GT	donor_gain	0.9900
2:85434913:A:T	donor_gain	0.9800
2:85434824:G:GT	donor_gain	0.9700
2:85435812:G:GT	donor_gain	0.9600
2:85435845:GGGCC:G	donor_gain	0.9500
2:85435412:GGACA:G	acceptor_gain	0.9400
2:85434867:TCAC:T	donor_gain	0.9300
2:85434868:C:A	donor_gain	0.9300
2:85434863:G:GT	donor_gain	0.9000
2:85435813:A:T	donor_gain	0.9000
2:85435391:G:GC	acceptor_gain	0.8900
2:85436592:G:GT	donor_gain	0.8900
2:85435407:GCAC:G	acceptor_loss	0.8700
2:85435408:CACA:C	acceptor_loss	0.8700
2:85435411:A:AC	acceptor_loss	0.8700
2:85435412:G:GA	acceptor_loss	0.8700
2:85435781:G:GT	donor_gain	0.8700
2:85435822:G:T	donor_gain	0.8600
2:85435838:G:GT	donor_gain	0.8600
2:85435411:A:AG	acceptor_gain	0.8500
2:85435412:G:GG	acceptor_gain	0.8500
2:85435307:T:G	donor_gain	0.8300
2:85435492:AAAAG:A	donor_loss	0.8300
2:85435493:AAAG:A	donor_loss	0.8300
2:85435494:AAGG:A	donor_loss	0.8300
2:85435495:AGG:A	donor_loss	0.8300
2:85435496:GG:G	donor_loss	0.8300
2:85435498:T:G	donor_loss	0.8300
2:85436809:A:G	acceptor_gain	0.8300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000089229 (2:85425740 A>T), RS1000308684 (2:85432691 C>T), RS1000524752 (2:85425269 T>A,C), RS1000539080 (2:85420821 C>A,T), RS1000556530 (2:85420492 G>A,C), RS1000961958 (2:85432510 C>T), RS1001126350 (2:85426862 G>A), RS1001179628 (2:85420346 C>G), RS1001480703 (2:85422074 C>T), RS1001533212 (2:85422370 T>C,G), RS1001601296 (2:85431900 T>C), RS1001941273 (2:85434463 T>C), RS1001998955 (2:85419736 G>C), RS1002348135 (2:85420005 G>A,C,T), RS1002490161 (2:85436512 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000189_9	Protein quantitative trait loci	7.000000e-06
GCST003927_6	Dysmenorrheic pain	8.000000e-07
GCST004599_277	Mean platelet volume	4.000000e-11
GCST006586_4	Urinary albumin excretion	4.000000e-10
GCST010866_36	Coronary artery disease	2.000000e-30
GCST010867_53	Coronary artery disease	7.000000e-10
GCST90002395_330	Mean platelet volume	4.000000e-21
GCST90002402_241	Platelet count	1.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004814	interleukin-6 receptor measurement
EFO:0007889	dysmenorrheic pain measurement
EFO:0004285	albuminuria
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
bisphenol S	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Endosulfan	increases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.