SH3BGR

Summary

SH3BGR (SH3 domain binding glutamate rich protein, HGNC:10822) is a protein-coding gene on chromosome 21q22.2, encoding SH3 domain-binding glutamic acid-rich protein (P55822).

Predicted to enable SH3 domain binding activity. Predicted to be active in cytoplasm.

Source: NCBI Gene 6450 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_007341

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10822
Approved symbol	SH3BGR
Name	SH3 domain binding glutamate rich protein
Location	21q22.2
Locus type	gene with protein product
Status	Approved
Aliases	21-GARP
Ensembl gene	ENSG00000185437
Ensembl biotype	protein_coding
OMIM	602230
Entrez	6450

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000333634, ENST00000380631, ENST00000380634, ENST00000380637, ENST00000423596, ENST00000440288, ENST00000447939, ENST00000452550, ENST00000458295, ENST00000698170, ENST00000877949, ENST00000940749, ENST00000946277, ENST00000946278

RefSeq mRNA: 5 — MANE Select: NM_007341 NM_001001713, NM_001317740, NM_001317741, NM_001317742, NM_007341

CCDS: CCDS13666, CCDS33560, CCDS82675

Canonical transcript exons

ENST00000333634 — 7 exons

Exon	Start	End
ENSE00001290961	39451970	39452141
ENSE00001291003	39508998	39509027
ENSE00001304806	39499823	39499915
ENSE00001318388	39511680	39511809
ENSE00001325607	39475135	39475215
ENSE00003570356	39462375	39462560
ENSE00003918592	39515088	39515504

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.6482 / max 514.2678, expressed in 1263 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189166	2.1827	1051
189171	1.5751	209
189170	1.2439	347
189169	1.0376	321
189173	0.2346	69
189174	0.1903	76
189167	0.0909	47
189172	0.0572	31
189168	0.0360	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	99.21	gold quality
skeletal muscle tissue	UBERON:0001134	99.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.90	gold quality
muscle of leg	UBERON:0001383	98.56	gold quality
heart left ventricle	UBERON:0002084	97.44	gold quality
apex of heart	UBERON:0002098	96.92	gold quality
heart	UBERON:0000948	96.75	gold quality
right atrium auricular region	UBERON:0006631	96.68	gold quality
right coronary artery	UBERON:0001625	96.13	gold quality
ascending aorta	UBERON:0001496	95.30	gold quality
thoracic aorta	UBERON:0001515	95.27	gold quality
muscle tissue	UBERON:0002385	95.00	gold quality
descending thoracic aorta	UBERON:0002345	94.34	gold quality
left coronary artery	UBERON:0001626	94.20	gold quality
popliteal artery	UBERON:0002250	93.86	gold quality
tibial artery	UBERON:0007610	93.85	gold quality
substantia nigra	UBERON:0002038	93.55	gold quality
putamen	UBERON:0001874	93.53	gold quality
nucleus accumbens	UBERON:0001882	93.37	gold quality
amygdala	UBERON:0001876	93.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.16	gold quality
caudate nucleus	UBERON:0001873	93.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.07	gold quality
lower esophagus	UBERON:0013473	93.02	gold quality
temporal lobe	UBERON:0001871	92.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.91	gold quality
Ammon’s horn	UBERON:0001954	92.84	gold quality
hypothalamus	UBERON:0001898	92.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.97	gold quality
adenohypophysis	UBERON:0002196	90.82	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

50 targeting SH3BGR, 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-126-5P	100.00	72.71	3180
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053

Literature-anchored findings (GeneRIF, showing 1)

• RNA-seq evidence of biallelic expression of SH3BGR and 10 neighboring genes in at least one primary human tissue tested indicates that the expression of SH3BGR is uncoupled from the control of the maternally inherited 5mCpG imprints at the WRB differentially methylated region (DMR) in disomic controls or trisomy (Down syndrome) individuals. (PMID:27100087)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3bgr	ENSDARG00000021633
mus_musculus	Sh3bgr	ENSMUSG00000040666
rattus_norvegicus	Sh3bgr	ENSRNOG00000028238

Paralogs (3): SH3BGRL (ENSG00000131171), SH3BGRL3 (ENSG00000142669), SH3BGRL2 (ENSG00000198478)

Protein

Protein identifiers

SH3 domain-binding glutamic acid-rich protein — P55822 (reviewed: P55822)

Alternative names: 21-glutamic acid-rich protein

All UniProt accessions (8): A0A804CBI3, A0A8V8TLG3, C9JJT2, C9JX40, H7C1Y8, H7C2G0, H7C3V3, P55822

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in heart and skeletal muscle.

Similarity. Belongs to the SH3BGR family.

Isoforms (2)

UniProt ID	Names	Canonical?
P55822-1	1	yes
P55822-2	2

RefSeq proteins (5): NP_001001713, NP_001304669, NP_001304670, NP_001304671, NP_031367* (*=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 (10 total): sequence variant 3, compositionally biased region 2, chain 1, region of interest 1, short sequence motif 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55822-F1	67.44	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, MODULE_66, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, DELYS_THYROID_CANCER_DN, TGACATY_UNKNOWN, TSENG_IRS1_TARGETS_DN, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, KANG_IMMORTALIZED_BY_TERT_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, MODULE_11, chr21q22, SMITH_TERT_TARGETS_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_16

GO Biological Process (0):

GO Molecular Function (2): SH3 domain binding (GO:0017124), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3BGR	HMGN1	P05114	875
SH3BGR	CNGB1	Q14028	773
SH3BGR	LCA5L	O95447	651
SH3BGR	PSMG1	O95456	624
SH3BGR	MTMR9	Q96QG7	434
SH3BGR	XKR6	Q5GH73	432
SH3BGR	EIF2B3	Q9NR50	425
SH3BGR	PDIA2	Q13087	416
SH3BGR	IMPA1	P29218	416
SH3BGR	RIPPLY3	P57055	413
SH3BGR	GOSR1	O95249	411
SH3BGR	CDK2AP1	O14519	406
SH3BGR	OSBPL8	Q9BZF1	405
SH3BGR	ACADSB	P45954	405
SH3BGR	FUT3	P21217	398
SH3BGR	BRWD1	Q9NSI6	398

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SH3BGR	DCP1B	psi-mi:“MI:0915”(physical association)	0.590
DEFB127	DCTN6	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	SH3BGR	psi-mi:“MI:0915”(physical association)	0.400
SH3BGR	FCHSD2	psi-mi:“MI:0915”(physical association)	0.000
SH3BGR		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): DCP1B (Affinity Capture-MS), SH3BGR (Affinity Capture-MS), SH3BGR (Affinity Capture-MS), SH3BGR (Affinity Capture-RNA), SH3BGR (Affinity Capture-RNA), SH3BGR (Affinity Capture-MS), DCP1B (Affinity Capture-MS), TRNAU1AP (Co-fractionation), SH3BGR (Two-hybrid), SH3BGR (Two-hybrid)

ESM2 similar proteins: A1XQU7, A6QLZ1, A7ER98, A8MWX3, A9CB93, F1N8V3, F4IXN6, O24413, P02260, P14201, P20810, P20811, P35722, P41110, P54877, P55822, P56724, P60761, P84286, Q04940, Q07266, Q16643, Q32NA2, Q32PF3, Q3ZBM6, Q5FWN9, Q5RCI9, Q6PGL7, Q6ZQ03, Q717R8, Q7TP40, Q80X08, Q8I6U3, Q8N6N3, Q8R1R5, Q8SUD4, Q8TDB4, Q8WW12, Q92686, Q95208

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1419 predictions. Top by Δscore:

Variant	Effect	Δscore
21:39462373:A:AG	acceptor_gain	1.0000
21:39462374:G:GG	acceptor_gain	1.0000
21:39462374:GAT:G	acceptor_gain	1.0000
21:39462374:GATTA:G	acceptor_gain	1.0000
21:39462556:GTGGG:G	donor_gain	1.0000
21:39462558:GGG:G	donor_gain	1.0000
21:39462559:GG:G	donor_gain	1.0000
21:39462559:GGG:G	donor_gain	1.0000
21:39462560:GG:G	donor_gain	1.0000
21:39462561:G:GG	donor_gain	1.0000
21:39462561:GTG:G	donor_loss	1.0000
21:39462562:T:G	donor_loss	1.0000
21:39462565:G:GG	donor_gain	1.0000
21:39475130:TCAA:T	acceptor_loss	1.0000
21:39475131:CAAG:C	acceptor_loss	1.0000
21:39475132:AAG:A	acceptor_gain	1.0000
21:39475133:A:G	acceptor_gain	1.0000
21:39475134:G:GG	acceptor_gain	1.0000
21:39475214:AGGT:A	donor_loss	1.0000
21:39475216:G:GG	donor_gain	1.0000
21:39475216:G:T	donor_loss	1.0000
21:39475217:T:G	donor_loss	1.0000
21:39508976:A:AG	acceptor_gain	1.0000
21:39508981:T:TA	acceptor_gain	1.0000
21:39515084:TTAGA:T	acceptor_loss	1.0000
21:39515085:TAG:T	acceptor_loss	1.0000
21:39515086:A:AG	acceptor_gain	1.0000
21:39515086:A:C	acceptor_loss	1.0000
21:39515087:G:GG	acceptor_gain	1.0000
21:39515087:GA:G	acceptor_gain	1.0000

AlphaMissense

1579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:39462405:T:C	F89L	1.000
21:39462407:T:A	F89L	1.000
21:39462407:T:G	F89L	1.000
21:39462409:T:C	L90S	1.000
21:39462475:T:C	M112T	1.000
21:39462537:T:C	F133L	1.000
21:39462539:C:A	F133L	1.000
21:39462539:C:G	F133L	1.000
21:39475183:T:C	F157L	1.000
21:39475185:C:A	F157L	1.000
21:39475185:C:G	F157L	1.000
21:39452112:T:C	F69L	0.999
21:39452114:T:A	F69L	0.999
21:39452114:T:G	F69L	0.999
21:39462389:G:C	Q83H	0.999
21:39462389:G:T	Q83H	0.999
21:39462406:T:C	F89S	0.999
21:39462406:T:G	F89C	0.999
21:39462445:T:A	I102N	0.999
21:39462467:G:C	R109S	0.999
21:39462467:G:T	R109S	0.999
21:39462476:G:A	M112I	0.999
21:39462476:G:C	M112I	0.999
21:39462476:G:T	M112I	0.999
21:39462528:C:T	P130S	0.999
21:39462529:C:A	P130H	0.999
21:39462535:T:C	I132T	0.999
21:39462535:T:G	I132S	0.999
21:39462538:T:C	F133S	0.999
21:39462559:G:A	G140E	0.999

dbSNP variants (sampled 300 via entrez): RS1000053625 (21:39461689 G>C), RS1000111115 (21:39507678 T>C), RS1000134360 (21:39445607 T>G), RS1000193512 (21:39489492 A>G), RS1000238207 (21:39486120 A>G,T), RS1000254142 (21:39492262 C>A), RS1000256787 (21:39454999 T>G), RS1000286215 (21:39473774 A>G), RS1000359383 (21:39501587 T>C), RS1000392121 (21:39495742 A>G), RS1000398480 (21:39451112 C>T), RS1000418611 (21:39472114 A>G), RS1000450450 (21:39501293 T>G), RS1000460081 (21:39457599 G>C), RS1000477041 (21:39498191 A>C)

Disease associations

OMIM: gene MIM:602230 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
bisphenol A	increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Copper	affects cotreatment, increases expression, affects binding	2
Doxorubicin	decreases expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
methylselenic acid	increases expression	1
stearic acid	increases expression	1
hydroquinone	increases expression	1
tetrachlorodian	decreases expression	1
avobenzone	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Carbamazepine	affects expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Tunicamycin	increases expression	1

Clinical trials (associated diseases)

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