SH3BGRL3

Summary

SH3BGRL3 (SH3 domain binding glutamate rich protein like 3, HGNC:15568) is a protein-coding gene on chromosome 1p36.11, encoding SH3 domain-binding glutamic acid-rich-like protein 3 (Q9H299). Could act as a modulator of glutaredoxin biological activity.

Involved in cytoskeleton organization. Located in cytosol; nuclear body; and ruffle membrane.

Source: NCBI Gene 83442 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_031286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15568
Approved symbol	SH3BGRL3
Name	SH3 domain binding glutamate rich protein like 3
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142669
Ensembl biotype	protein_coding
OMIM	615679
Entrez	83442

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000270792, ENST00000319041, ENST00000879853, ENST00000879854, ENST00000934910, ENST00000934911, ENST00000934912

RefSeq mRNA: 1 — MANE Select: NM_031286 NM_031286

CCDS: CCDS278

Canonical transcript exons

ENST00000270792 — 3 exons

Exon	Start	End
ENSE00000955749	26280765	26280932
ENSE00001462874	26280086	26280203
ENSE00003715226	26281058	26281522

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 917.4225 / max 8541.0934, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1579	880.2226	1826
1580	37.1078	1793
1578	0.0920	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.76	gold quality
monocyte	CL:0000576	99.71	gold quality
leukocyte	CL:0000738	99.68	gold quality
mononuclear cell	CL:0000842	99.67	gold quality
mucosa of transverse colon	UBERON:0004991	99.57	gold quality
lower esophagus mucosa	UBERON:0035834	99.49	gold quality
right lung	UBERON:0002167	99.35	gold quality
descending thoracic aorta	UBERON:0002345	99.34	gold quality
thoracic aorta	UBERON:0001515	99.33	gold quality
ascending aorta	UBERON:0001496	99.32	gold quality
rectum	UBERON:0001052	99.31	gold quality
skin of abdomen	UBERON:0001416	99.27	gold quality
spleen	UBERON:0002106	99.26	gold quality
upper lobe of left lung	UBERON:0008952	99.26	gold quality
left coronary artery	UBERON:0001626	99.25	gold quality
right coronary artery	UBERON:0001625	99.22	gold quality
skin of leg	UBERON:0001511	99.21	gold quality
transverse colon	UBERON:0001157	99.15	gold quality
stromal cell of endometrium	CL:0002255	99.12	gold quality
coronary artery	UBERON:0001621	99.10	gold quality
blood	UBERON:0000178	99.07	gold quality
upper lobe of lung	UBERON:0008948	99.05	gold quality
esophagus mucosa	UBERON:0002469	99.04	gold quality
omental fat pad	UBERON:0010414	99.04	gold quality
lymph node	UBERON:0000029	99.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.03	gold quality
body of stomach	UBERON:0001161	99.02	gold quality
peritoneum	UBERON:0002358	99.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.99	gold quality
aorta	UBERON:0000947	98.98	gold quality

Single-cell (SCXA)

Detected in 56 experiment(s), a significant marker in 37.

Experiment	Marker?	Max mean expression
E-MTAB-10432	yes	10546.49
E-MTAB-8142	yes	5557.04
E-MTAB-10042	yes	3310.12
E-GEOD-111727	yes	3175.02
E-GEOD-75367	yes	2811.38
E-MTAB-9841	yes	2359.18
E-MTAB-11121	yes	2210.46
E-GEOD-84465	yes	2142.49
E-GEOD-125970	yes	1423.09
E-MTAB-10283	yes	1103.32
E-GEOD-81383	yes	769.91
E-HCAD-4	yes	300.94
E-HCAD-1	yes	105.79
E-MTAB-6701	yes	98.94
E-CURD-122	yes	86.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting SH3BGRL3, 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-6758-5P	100.00	66.21	1470
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490

Literature-anchored findings (GeneRIF, showing 5)

• SH3BGRL3 may function as a regulator in all-trans retinoic acid-induced pathway (PMID:15907482)
• SH3BGRL3 is a novel urinary biomarker for urothelial carcinoma. Evaluation of SH3BGRL3 expression status may identify a subset of patients with urothelial carcinoma for cotargeting candidates in the design of EGFR-based cancer therapies. (PMID:26286913)
• SH3BGRL confers innate drug resistance in breast cancer by stabilizing HER2 activation on cell membrane. (PMID:32381043)
• SH3BGRL3, transcribed by STAT3, facilitates glioblastoma tumorigenesis by activating STAT3 signaling. (PMID:33839406)
• SH3BGRL3 binds to myosin 1c in a calcium dependent manner and modulates migration in the MDA-MB-231 cell line. (PMID:34380438)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3bgrl3	ENSDARG00000098075
mus_musculus	Sh3bgrl3	ENSMUSG00000028843
rattus_norvegicus	Sh3bgrl3	ENSRNOG00000015967

Paralogs (3): SH3BGRL (ENSG00000131171), SH3BGR (ENSG00000185437), SH3BGRL2 (ENSG00000198478)

Protein

Protein identifiers

SH3 domain-binding glutamic acid-rich-like protein 3 — Q9H299 (reviewed: Q9H299)

Alternative names: SH3 domain-binding protein 1, TNF inhibitory protein B1

All UniProt accessions (2): Q9H299, Q5T123

UniProt curated annotations — full annotation on UniProt →

Function. Could act as a modulator of glutaredoxin biological activity. May play a role in cytoskeleton organization.

Subunit / interactions. Homodimer. Interacts with MYO1C (via its IQ motifs); the interaction is dependent on calcium and takes place at membrane ruffles.

Subcellular location. Cytoplasm. Cytosol. Cell projection. Ruffle membrane. Nucleus.

Tissue specificity. Ubiquitous. Expressed in heart, kidney and liver (at protein level). Expressed in brain, lung, spleen and skeletal muscle.

Post-translational modifications. May be glycosylated.

Similarity. Belongs to the SH3BGR family.

RefSeq proteins (1): NP_112576* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006993	Glut_rich_SH3-bd	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR051033	SH3BGR	Family

Pfam: PF04908

UniProt features (14 total): strand 4, helix 4, initiator methionine 1, chain 1, turn 1, domain 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1SJ6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H299-F1	96.44	0.97

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): 2

Glycosylation sites (1): 9

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 226 (showing top): MYOGENIN_Q6, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOCC_RUFFLE, CAGCTG_AP4_Q5, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, NKX61_01, RICKMAN_METASTASIS_DN, ONKEN_UVEAL_MELANOMA_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, MCAATNNNNNGCG_UNKNOWN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GNF2_ICAM3, GNF2_S100A4

GO Biological Process (1): cytoskeleton organization (GO:0007010)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), ruffle membrane (GO:0032587), extracellular exosome (GO:0070062), nucleus (GO:0005634), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
organelle organization	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3BGRL3	TMSB4X	P01253	512
SH3BGRL3	PFN1	P07737	495
SH3BGRL3	CFL1	P23528	480
SH3BGRL3	TAGLN2	P37802	473
SH3BGRL3	EGFR	P00533	462
SH3BGRL3	CSRP1	P21291	437
SH3BGRL3	CALML3	P27482	435
SH3BGRL3	TXNDC11	Q6PKC3	435
SH3BGRL3	TBCK	Q8TEA7	429
SH3BGRL3	GNAZ	P19086	424
SH3BGRL3	CALML6	Q8TD86	421
SH3BGRL3	CALML4	Q96GE6	421
SH3BGRL3	CALML5	Q9NZT1	421
SH3BGRL3	CALM1	P02593	418
SH3BGRL3	PLIN3	O60664	400

IntAct

22 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
DDIT4L	SH3BGRL3	psi-mi:“MI:0915”(physical association)	0.560
EGFR	SH3BGRL3	psi-mi:“MI:0915”(physical association)	0.550
SH3BGRL3	EGFR	psi-mi:“MI:0915”(physical association)	0.550
SH3BGRL3	PCP4	psi-mi:“MI:0914”(association)	0.530
SH3BGRL3	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
SH3BGRL3	ERBB2	psi-mi:“MI:0915”(physical association)	0.400
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
BCAR1	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
BCAR1	CEP290	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
rep	CALU	psi-mi:“MI:0914”(association)	0.350
	PDLIM1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PCP4	RAB39B	psi-mi:“MI:0914”(association)	0.350
ATF2	ABLIM1	psi-mi:“MI:0914”(association)	0.350
CEBPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
STAT3	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
SH3BGRL3	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (68): SH3BGRL3 (Affinity Capture-MS), SH3BGRL3 (Affinity Capture-MS), SUCLA2 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), GRPEL1 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation), SH3BGRL3 (Co-fractionation)

ESM2 similar proteins: A1A4Q2, A6NEY8, B2RZ27, E9QI36, O06465, O75131, O76003, O81187, P0A155, P0A156, P12081, P19480, P35340, P55143, Q28EX9, Q28ID3, Q2KI84, Q2KJD7, Q3ZCL8, Q4I963, Q58DA7, Q5FWT7, Q5R4C4, Q5R4R2, Q5RAE1, Q5RC61, Q5XJ54, Q5ZJJ8, Q61035, Q641F1, Q6DBT3, Q6DI37, Q7KLV9, Q80T18, Q80Y14, Q86SX6, Q8BGR9, Q8CI33, Q8K3X2, Q8WVY7

Diamond homologs: A4IFC4, B2RZ27, O75368, P55822, Q28FJ0, Q3KPU0, Q3ZCL8, Q4R7R5, Q58DU7, Q5RC61, Q5REQ9, Q5RFN7, Q6GMK7, Q7T0M3, Q8BG73, Q91VW3, Q9H299, Q9JJU8, Q9NFP5, Q9UJC5, Q9WUZ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
nervous system development	5	10.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

253 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26280199:GCGAA:G	donor_gain	1.0000
1:26280204:G:GG	donor_gain	1.0000
1:26280756:T:TA	acceptor_gain	1.0000
1:26280761:CCA:C	acceptor_loss	1.0000
1:26280761:CCAGA:C	acceptor_gain	1.0000
1:26280762:CAG:C	acceptor_gain	1.0000
1:26280763:A:AG	acceptor_gain	1.0000
1:26280763:A:T	acceptor_loss	1.0000
1:26280763:AGA:A	acceptor_gain	1.0000
1:26280764:G:GT	acceptor_gain	1.0000
1:26280764:GA:G	acceptor_gain	1.0000
1:26280764:GAT:G	acceptor_gain	1.0000
1:26280764:GATC:G	acceptor_gain	1.0000
1:26280764:GATCA:G	acceptor_gain	1.0000
1:26280857:GGA:G	donor_gain	1.0000
1:26280858:G:T	donor_gain	1.0000
1:26280877:C:T	donor_gain	1.0000
1:26280923:GTACT:G	donor_gain	1.0000
1:26280928:GTGGG:G	donor_gain	1.0000
1:26280930:GGG:G	donor_gain	1.0000
1:26280931:GGG:G	donor_gain	1.0000
1:26280200:CGAA:C	donor_gain	0.9900
1:26280201:GAA:G	donor_gain	0.9900
1:26280201:GAAG:G	donor_gain	0.9900
1:26280202:AA:A	donor_gain	0.9900
1:26280203:AG:A	donor_loss	0.9900
1:26280204:G:T	donor_loss	0.9900
1:26280205:T:A	donor_loss	0.9900
1:26280760:CCCA:C	acceptor_gain	0.9900
1:26280764:G:C	acceptor_gain	0.9900

AlphaMissense

600 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26280793:G:C	R26P	0.998
1:26280865:T:C	M50T	0.997
1:26280868:G:C	R51P	0.997
1:26280901:C:A	P62H	0.997
1:26280931:G:A	G72E	0.997
1:26281079:G:C	A80P	0.997
1:26281106:T:C	F89L	0.997
1:26281108:C:A	F89L	0.997
1:26281108:C:G	F89L	0.997
1:26280907:T:A	I64N	0.996
1:26280778:A:C	Q21P	0.995
1:26280799:T:C	L28P	0.995
1:26280831:G:C	D39H	0.995
1:26280900:C:T	P62S	0.995
1:26280907:T:G	I64S	0.995
1:26280930:G:T	G72W	0.995
1:26280931:G:T	G72V	0.995
1:26281071:T:C	F77S	0.995
1:26280832:A:C	D39A	0.994
1:26280832:A:G	D39G	0.994
1:26280857:G:C	R47S	0.994
1:26280857:G:T	R47S	0.994
1:26280866:G:A	M50I	0.994
1:26280866:G:C	M50I	0.994
1:26280866:G:T	M50I	0.994
1:26281107:T:C	F89S	0.994
1:26280771:T:C	S19P	0.993
1:26280799:T:A	L28Q	0.993
1:26280833:C:A	D39E	0.993
1:26280833:C:G	D39E	0.993

dbSNP variants (sampled 300 via entrez): RS1000159614 (1:26280296 G>A,T), RS1001179765 (1:26280488 G>T), RS1001649479 (1:26279433 T>C), RS1001804078 (1:26279712 C>T), RS1002219626 (1:26279771 T>C), RS1002753433 (1:26278524 A>T), RS1003628319 (1:26278230 C>T), RS1003824645 (1:26281972 T>C), RS1004424592 (1:26280581 C>T), RS1004691425 (1:26280856 G>A,T), RS1005126465 (1:26281519 G>A), RS1006248154 (1:26279353 A>C), RS1006285150 (1:26279116 G>A,C), RS1006541067 (1:26280240 C>T), RS1008468774 (1:26281154 C>T)

Disease associations

OMIM: gene MIM:615679 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	5
Benzo(a)pyrene	increases expression, increases methylation	4
bisphenol A	affects expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
chloropicrin	affects expression, decreases expression	2
Arsenic Trioxide	increases expression, decreases expression, affects cotreatment	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression, affects cotreatment	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	increases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
periodate-oxidized adenosine	affects expression	1
cupric chloride	increases expression	1
CD 437	decreases expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GY	Abcam HEK293T SH3BGRL3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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