SHE

Summary

SHE (Src homology 2 domain containing E, HGNC:27004) is a protein-coding gene on chromosome 1q21.3, encoding SH2 domain-containing adapter protein E (Q5VZ18).

Predicted to enable phosphotyrosine residue binding activity.

Source: NCBI Gene 126669 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_001010846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27004
Approved symbol	SHE
Name	Src homology 2 domain containing E
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169291
Ensembl biotype	protein_coding
OMIM	610482
Entrez	126669

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000304760, ENST00000486773, ENST00000555188, ENST00000960431, ENST00000960432

RefSeq mRNA: 1 — MANE Select: NM_001010846 NM_001010846

CCDS: CCDS30877

Canonical transcript exons

ENST00000304760 — 6 exons

Exon	Start	End
ENSE00001174452	154485943	154486062
ENSE00001174457	154486527	154486683
ENSE00001174461	154489051	154489356
ENSE00001174467	154499112	154499238
ENSE00001200869	154479481	154484335
ENSE00001281479	154501436	154502412

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 96.74.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6123 / max 53.7506, expressed in 345 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14813	0.9381	272
14812	0.4687	219
14814	0.1126	53
14811	0.0929	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	96.74	gold quality
left ventricle myocardium	UBERON:0006566	95.72	gold quality
oocyte	CL:0000023	94.42	gold quality
secondary oocyte	CL:0000655	94.20	gold quality
myocardium	UBERON:0002349	92.44	gold quality
parietal pleura	UBERON:0002400	91.67	gold quality
visceral pleura	UBERON:0002401	91.16	gold quality
right lung	UBERON:0002167	89.73	gold quality
lower lobe of lung	UBERON:0008949	89.39	gold quality
apex of heart	UBERON:0002098	89.23	gold quality
omental fat pad	UBERON:0010414	89.02	gold quality
right lobe of thyroid gland	UBERON:0001119	88.97	gold quality
peritoneum	UBERON:0002358	88.97	gold quality
left lobe of thyroid gland	UBERON:0001120	88.90	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.56	gold quality
thyroid gland	UBERON:0002046	88.34	gold quality
adipose tissue	UBERON:0001013	87.81	gold quality
kidney epithelium	UBERON:0004819	87.71	gold quality
upper lobe of left lung	UBERON:0008952	87.54	gold quality
upper lobe of lung	UBERON:0008948	87.53	gold quality
left testis	UBERON:0004533	87.47	gold quality
pericardium	UBERON:0002407	87.44	gold quality
germinal epithelium of ovary	UBERON:0001304	87.41	gold quality
spleen	UBERON:0002106	87.32	gold quality
tibialis anterior	UBERON:0001385	87.08	silver quality
lung	UBERON:0002048	87.05	gold quality
right testis	UBERON:0004534	86.90	gold quality
sperm	CL:0000019	86.40	gold quality
heart right ventricle	UBERON:0002080	86.35	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	15.33
E-MTAB-8498	yes	13.32
E-MTAB-9801	yes	8.44
E-ANND-3	yes	6.41
E-GEOD-76312	no	62.86
E-ENAD-27	no	4.10
E-GEOD-83139	no	3.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting SHE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 1)

• Reports data for mouse She and not human. (PMID:9315092)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	she	ENSDARG00000087956
mus_musculus	She	ENSMUSG00000046280
rattus_norvegicus	She	ENSRNOG00000020797

Paralogs (3): SHD (ENSG00000105251), SHB (ENSG00000107338), SHF (ENSG00000138606)

Protein

Protein identifiers

SH2 domain-containing adapter protein E — Q5VZ18 (reviewed: Q5VZ18)

All UniProt accessions (3): Q5VZ18, H0YJQ6, H0YJR4

RefSeq proteins (1): NP_001010846* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR035042	SHE_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051846	SH2_domain_adapters	Family

Pfam: PF00017

UniProt features (11 total): compositionally biased region 5, region of interest 3, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZ18-F1	59.79	0.19

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 107

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, GUO_HEX_TARGETS_DN, CUI_TCF21_TARGETS_2_DN, MCCLUNG_COCAIN_REWARD_4WK, chr1q21, GAVIN_FOXP3_TARGETS_CLUSTER_P7, GOMF_PHOSPHOPROTEIN_BINDING, GOMF_PROTEIN_PHOSPHORYLATED_AMINO_ACID_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MADAN_DPPA4_TARGETS, LIM_MAMMARY_STEM_CELL_UP, GOMF_PHOSPHOTYROSINE_RESIDUE_BINDING

GO Biological Process (0):

GO Molecular Function (2): phosphotyrosine residue binding (GO:0001784), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein phosphorylated amino acid binding	1
binding	1

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHE	SHC1	P29353	561
SHE	ZNF180	Q9UJW8	507
SHE	C3	P01024	450
SHE	SHD	Q96IW2	443
SHE	EPHX2	P34913	434
SHE	DRC7	Q8IY82	427
SHE	RALYL	Q86SE5	377
SHE	CDH17	Q12864	372
SHE	C6	P13671	367
SHE	AADAT	Q8N5Z0	353
SHE	RALY	Q9UKM9	352
SHE	ADCY3	O60266	352
SHE	EVX1	P49640	350
SHE	ZFP57	Q9NU63	348
SHE	TDRD10	Q5VZ19	305

IntAct

13 interactions, top by confidence:

A	B	Type	Score
FHL3	SHE	psi-mi:“MI:0915”(physical association)	0.560
TRIT1	SHE	psi-mi:“MI:0915”(physical association)	0.490
SHE	DOK3	psi-mi:“MI:0915”(physical association)	0.490
SHE	TRIT1	psi-mi:“MI:0915”(physical association)	0.490
DOK3	SHE	psi-mi:“MI:0915”(physical association)	0.490
SHE	AR	psi-mi:“MI:0407”(direct interaction)	0.440
MYC		psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
SHE	FHL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): DOK3 (Two-hybrid), TRIT1 (Two-hybrid), FGFR1 (Affinity Capture-Western), FHL3 (Two-hybrid), SHE (Reconstituted Complex), SHE (Reconstituted Complex), SHE (Two-hybrid), SHE (Affinity Capture-MS)

ESM2 similar proteins: A1L1I3, A5PKW4, O08919, O70405, O75385, O75420, O75553, P16554, P42128, P49757, P53814, P85037, P97318, P98081, Q04637, Q2LC84, Q3UCQ1, Q4KMP7, Q5DTT2, Q5I1X5, Q5RBR0, Q5VZ18, Q69ZH9, Q69ZI1, Q7TN02, Q7Z6J0, Q80VC9, Q80XI3, Q80Z38, Q86V15, Q8BGT6, Q8BHL3, Q8BSD5, Q8C120, Q8CI12, Q8IY33, Q8K4J6, Q8N3F8, Q8TEH3, Q8TEJ3

Diamond homologs: A6NKC9, A6X942, O09039, O45539, O88834, O89100, P00519, P00520, P00521, P00522, P06239, P09851, P10447, P16333, P20936, P29349, P29353, P35235, P41499, P42684, P42685, P42686, P50745, P50904, P98083, Q06124, Q08CX2, Q0IIE2, Q13882, Q15464, Q24708, Q4JIM5, Q54U31, Q5PXS1, Q5R7W7, Q5SQS7, Q5VZ18, Q62985, Q64434, Q6AYC8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1105 predictions. Top by Δscore:

Variant	Effect	Δscore
1:154485941:A:AC	donor_gain	1.0000
1:154485942:C:CC	donor_gain	1.0000
1:154485978:A:AC	donor_gain	1.0000
1:154485979:C:CC	donor_gain	1.0000
1:154486059:CCAG:C	acceptor_gain	1.0000
1:154486060:CAG:C	acceptor_gain	1.0000
1:154486060:CAGC:C	acceptor_gain	1.0000
1:154486061:AG:A	acceptor_gain	1.0000
1:154486062:GC:G	acceptor_loss	1.0000
1:154486063:C:CC	acceptor_gain	1.0000
1:154486063:CTG:C	acceptor_loss	1.0000
1:154486064:T:C	acceptor_loss	1.0000
1:154486070:A:AC	acceptor_gain	1.0000
1:154486070:A:C	acceptor_gain	1.0000
1:154486076:G:C	acceptor_gain	1.0000
1:154486076:G:GC	acceptor_gain	1.0000
1:154486525:A:AC	donor_gain	1.0000
1:154486526:C:CC	donor_gain	1.0000
1:154486526:CGG:C	donor_gain	1.0000
1:154486679:CTGGA:C	acceptor_gain	1.0000
1:154486684:C:CC	acceptor_gain	1.0000
1:154489045:CCTCA:C	donor_loss	1.0000
1:154489046:CTCA:C	donor_loss	1.0000
1:154489047:TCACC:T	donor_loss	1.0000
1:154489048:CAC:C	donor_loss	1.0000
1:154489049:A:C	donor_loss	1.0000
1:154499107:CAAA:C	donor_gain	1.0000
1:154499108:AAAC:A	donor_loss	1.0000
1:154499111:C:G	donor_loss	1.0000
1:154499234:ATGAC:A	acceptor_gain	1.0000

AlphaMissense

3204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154484180:A:G	L486S	1.000
1:154484210:A:G	L476S	1.000
1:154484316:G:C	H441D	1.000
1:154485946:A:G	L433P	1.000
1:154485949:G:T	A432D	1.000
1:154485952:A:T	I431N	1.000
1:154485985:C:G	R420P	1.000
1:154485988:A:T	V419D	1.000
1:154485991:A:G	L418P	1.000
1:154486061:A:G	W395R	1.000
1:154486061:A:T	W395R	1.000
1:154499117:A:G	I238T	1.000
1:154499117:A:T	I238K	1.000
1:154499138:G:T	P231Q	1.000
1:154499148:A:G	Y228H	1.000
1:154484210:A:C	L476W	0.999
1:154484254:A:C	F461L	0.999
1:154484254:A:T	F461L	0.999
1:154484256:A:G	F461L	0.999
1:154484276:A:G	L454P	0.999
1:154484306:A:T	V444E	0.999
1:154484312:A:T	I442N	0.999
1:154484314:G:C	H441Q	0.999
1:154484314:G:T	H441Q	0.999
1:154484315:T:C	H441R	0.999
1:154485946:A:T	L433Q	0.999
1:154485950:C:G	A432P	0.999
1:154485952:A:C	I431S	0.999
1:154485995:A:C	Y417D	0.999
1:154486018:A:G	L409P	0.999

dbSNP variants (sampled 300 via entrez): RS1000081201 (1:154501235 A>G), RS1000304809 (1:154471414 A>G), RS1000485114 (1:154499520 T>C), RS1000536320 (1:154501400 G>A,C,T), RS1000551432 (1:154503577 G>T), RS1000635525 (1:154469783 A>G), RS1000635770 (1:154498517 C>A), RS1000875176 (1:154476300 A>C), RS1000887671 (1:154481905 A>C,G), RS1001002943 (1:154482736 T>C), RS1001085639 (1:154487242 A>C,G), RS1001162139 (1:154473905 G>A), RS1001165611 (1:154489523 T>G), RS1001230334 (1:154498268 T>A), RS1001353981 (1:154495989 C>T)

Disease associations

OMIM: gene MIM:610482 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002665_2	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	6.000000e-63

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004810	interleukin-6 measurement
EFO:0006514	Alzheimer’s disease biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11265621	SHE		0.00	0

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
entinostat	increases expression, affects cotreatment	2
Calcitriol	increases expression	2
trichostatin A	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Cisplatin	affects expression	1
Dactinomycin	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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