SH3BGRL2

Summary

SH3BGRL2 (SH3 domain binding glutamate rich protein like 2, HGNC:15567) is a protein-coding gene on chromosome 6q14.1, encoding SH3 domain-binding glutamic acid-rich-like protein 2 (Q9UJC5).

Predicted to enable SH3 domain binding activity. Located in nuclear membrane and nucleoplasm.

Source: NCBI Gene 83699 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• MANE Select transcript: NM_031469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15567
Approved symbol	SH3BGRL2
Name	SH3 domain binding glutamate rich protein like 2
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198478
Ensembl biotype	protein_coding
OMIM	615678
Entrez	83699

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000369838, ENST00000607718, ENST00000623514, ENST00000671258, ENST00000691944, ENST00000692474, ENST00000718097, ENST00000718098, ENST00000718099, ENST00000718100, ENST00000718101, ENST00000718102, ENST00000718103, ENST00000718104, ENST00000718105, ENST00000718106, ENST00000718108, ENST00000899640, ENST00000899641, ENST00000949229

RefSeq mRNA: 1 — MANE Select: NM_031469 NM_031469

CCDS: CCDS4991

Canonical transcript exons

ENST00000369838 — 4 exons

Exon	Start	End
ENSE00001451030	79631329	79631506
ENSE00004034137	79673614	79673799
ENSE00004034204	79699498	79703655
ENSE00004034205	79696485	79696565

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.9818 / max 712.6525, expressed in 1607 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68678	6.1877	1291
68687	5.7084	767
68686	4.7087	960
68684	2.6007	1012
68677	1.1562	580
68680	1.1382	264
68685	0.7801	403
68688	0.6377	226
68693	0.4301	193
68683	0.2702	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.24	gold quality
ileal mucosa	UBERON:0000331	97.23	gold quality
esophagus squamous epithelium	UBERON:0006920	96.76	gold quality
amniotic fluid	UBERON:0000173	96.66	gold quality
lower esophagus mucosa	UBERON:0035834	96.29	gold quality
pons	UBERON:0000988	95.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.56	gold quality
rectum	UBERON:0001052	95.17	gold quality
substantia nigra pars compacta	UBERON:0001965	95.16	gold quality
middle temporal gyrus	UBERON:0002771	94.92	gold quality
colonic mucosa	UBERON:0000317	94.71	gold quality
monocyte	CL:0000576	94.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.21	gold quality
oral cavity	UBERON:0000167	94.02	gold quality
trachea	UBERON:0003126	93.91	gold quality
jejunal mucosa	UBERON:0000399	93.52	gold quality
leukocyte	CL:0000738	93.43	gold quality
saliva-secreting gland	UBERON:0001044	93.42	gold quality
dorsal root ganglion	UBERON:0000044	93.00	gold quality
urethra	UBERON:0000057	92.97	gold quality
postcentral gyrus	UBERON:0002581	92.81	gold quality
superior frontal gyrus	UBERON:0002661	92.80	gold quality
mucosa of transverse colon	UBERON:0004991	92.74	gold quality
thyroid gland	UBERON:0002046	92.72	gold quality
left lobe of thyroid gland	UBERON:0001120	92.52	gold quality
epithelial cell of pancreas	CL:0000083	92.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.34	gold quality
esophagus mucosa	UBERON:0002469	92.34	gold quality
duodenum	UBERON:0002114	92.18	gold quality
parietal lobe	UBERON:0001872	92.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-75367	no	1479.96
E-MTAB-6678	no	2.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

252 targeting SH3BGRL2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4692	100.00	67.32	2066

Literature-anchored findings (GeneRIF, showing 1)

• SH3BGRL2 functions as a crucial tumor suppressor in glioblastoma tumorigenesis. (PMID:33610914)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3bgrl2	ENSDARG00000036878
mus_musculus	Sh3bgrl2	ENSMUSG00000032261
rattus_norvegicus	Sh3bgrl2	ENSRNOG00000009613

Paralogs (3): SH3BGRL (ENSG00000131171), SH3BGRL3 (ENSG00000142669), SH3BGR (ENSG00000185437)

Protein

Protein identifiers

SH3 domain-binding glutamic acid-rich-like protein 2 — Q9UJC5 (reviewed: Q9UJC5)

Alternative names: Fovea-associated SH3 domain-binding protein

All UniProt accessions (1): Q9UJC5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in brain, placenta, liver and kidney. Expressed in retina.

Similarity. Belongs to the SH3BGR family.

RefSeq proteins (1): NP_113657* (*=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 (16 total): strand 5, helix 4, turn 3, sequence conflict 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CT6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJC5-F1	89.95	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 211 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GGGTGGRR_PAX4_03, AACWWCAANK_UNKNOWN, EVI1_05, TGCTGAY_UNKNOWN, WTGAAAT_UNKNOWN, NRF2_Q4, GFI1_01, CUI_TCF21_TARGETS_2_DN, IK3_01

GO Biological Process (0):

GO Molecular Function (1): SH3 domain binding (GO:0017124)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear membrane (GO:0031965), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein domain specific binding	1
nuclear lumen	1
intracellular anatomical structure	1
nucleus	1
nuclear envelope	1
organelle membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3BGRL2	GPRIN3	Q6ZVF9	455
SH3BGRL2	IRF8	Q02556	398
SH3BGRL2	MTURN	Q8N3F0	396
SH3BGRL2	LCA5	Q86VQ0	392
SH3BGRL2	CALY	Q9NYX4	344
SH3BGRL2	LRRIQ1	Q96JM4	340
SH3BGRL2	NGRN	Q9NPE2	338
SH3BGRL2	MXD4	Q14582	336
SH3BGRL2	FILIP1	Q7Z7B0	325
SH3BGRL2	TSPAN12	O95859	323
SH3BGRL2	RUNDC3A	Q59EK9	323
SH3BGRL2	CFAP95	Q5VTT2	318
SH3BGRL2	MTFR1L	Q9H019	305
SH3BGRL2	PTPRK	Q15262	295
SH3BGRL2	NISCH	Q9Y2I1	292

IntAct

14 interactions, top by confidence:

A	B	Type	Score
DBN1	SVIL	psi-mi:“MI:0914”(association)	0.530
PCNA	SH3BGRL2	psi-mi:“MI:0915”(physical association)	0.370
CFTR		psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
MAB21L2	PTBP1	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
DAPK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
TMOD1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ORF24	MVK	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS), SH3BGRL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN48, A4IFC4, C9K7C5, O16115, P0DOQ9, P0DOR0, P17695, P25373, P32642, P34348, P68690, P68691, P68692, P79764, P85801, Q05926, Q06597, Q09433, Q19297, Q1RHJ0, Q28FJ0, Q29238, Q3KPU0, Q4UKL7, Q54EX7, Q5REQ9, Q5UR29, Q68XG4, Q6GMK7, Q6RZN3, Q76ZV3, Q775X4, Q77TL9, Q7T0M3, Q80E01, Q8JLF5, Q8QMY9, Q8V2V1, Q8VZQ0, Q8WZK3

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
969	NC_000006.12:g.79536910_79538507del	Pathogenic

SpliceAI

1169 predictions. Top by Δscore:

Variant	Effect	Δscore
6:79537220:C:A	donor_gain	1.0000
6:79673612:A:AG	acceptor_gain	1.0000
6:79673612:AGA:A	acceptor_loss	1.0000
6:79673613:G:GA	acceptor_gain	1.0000
6:79673613:GA:G	acceptor_gain	1.0000
6:79673613:GAT:G	acceptor_gain	1.0000
6:79673613:GATAA:G	acceptor_gain	1.0000
6:79673795:GTGGA:G	donor_gain	1.0000
6:79673796:TGGA:T	donor_gain	1.0000
6:79673797:GGA:G	donor_gain	1.0000
6:79673797:GGAG:G	donor_gain	1.0000
6:79673798:GA:G	donor_gain	1.0000
6:79673798:GAG:G	donor_gain	1.0000
6:79673799:AGTA:A	donor_loss	1.0000
6:79673800:G:GG	donor_gain	1.0000
6:79673800:GTA:G	donor_loss	1.0000
6:79673801:TAA:T	donor_loss	1.0000
6:79673802:AA:A	donor_loss	1.0000
6:79696565:GGTA:G	donor_loss	1.0000
6:79696567:T:G	donor_loss	1.0000
6:79699493:TATA:T	acceptor_loss	1.0000
6:79699495:TA:T	acceptor_loss	1.0000
6:79699496:A:C	acceptor_loss	1.0000
6:79631503:GGCG:G	donor_gain	0.9900
6:79631504:GCG:G	donor_gain	0.9900
6:79631504:GCGG:G	donor_gain	0.9900
6:79631505:CGG:C	donor_loss	0.9900
6:79631507:G:GG	donor_gain	0.9900
6:79631507:G:T	donor_loss	0.9900
6:79631508:T:G	donor_loss	0.9900

AlphaMissense

704 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:79673768:C:A	P67H	0.994
6:79673774:T:A	I69K	0.992
6:79673776:T:C	F70L	0.992
6:79673778:T:A	F70L	0.992
6:79673778:T:G	F70L	0.992
6:79673644:T:C	F26L	0.991
6:79673646:T:A	F26L	0.991
6:79673646:T:G	F26L	0.991
6:79673706:G:C	R46S	0.990
6:79673706:G:T	R46S	0.990
6:79673767:C:T	P67S	0.990
6:79673648:T:C	L27P	0.989
6:79673714:T:C	M49T	0.989
6:79673765:C:A	P66Q	0.989
6:79673774:T:C	I69T	0.989
6:79631477:T:C	F6L	0.988
6:79631479:C:A	F6L	0.988
6:79631479:C:G	F6L	0.988
6:79673628:G:C	Q20H	0.988
6:79673628:G:T	Q20H	0.988
6:79673648:T:A	L27Q	0.987
6:79673767:C:A	P67T	0.987
6:79673774:T:G	I69R	0.987
6:79673798:G:A	G77E	0.987
6:79673680:G:C	D38H	0.986
6:79673768:C:G	P67R	0.986
6:79696533:T:C	F94L	0.986
6:79696535:T:A	F94L	0.986
6:79696535:T:G	F94L	0.986
6:79696511:G:C	K86N	0.985

dbSNP variants (sampled 300 via entrez): RS1000002219 (6:79591975 G>A), RS1000004944 (6:79550478 T>C), RS1000026946 (6:79537568 C>T), RS1000043716 (6:79587138 TTAAAG>T), RS1000058457 (6:79539817 G>A,C,T), RS1000103398 (6:79545068 T>C), RS1000147502 (6:79694484 T>C), RS1000155141 (6:79685630 A>AT), RS1000155894 (6:79629376 G>C), RS1000174868 (6:79638390 A>T), RS1000179026 (6:79670490 A>G), RS1000189753 (6:79584179 A>G), RS1000200539 (6:79627073 T>C), RS1000216567 (6:79643513 A>G), RS1000225827 (6:79557029 A>G)

Disease associations

OMIM: gene MIM:615678 | disease phenotypes: MIM:604537

GenCC curated gene-disease

Mondo (1): Leber congenital amaurosis 5 (MONDO:0011473)

Orphanet (1): Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000691_5	Partial epilepsies	3.000000e-07
GCST001599_3	Aging	1.000000e-06
GCST002690_8	Very long-chain saturated fatty acid levels (fatty acid 20:0)	4.000000e-06
GCST002989_14	LDL peak particle diameter (total fat intake interaction)	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0007677	LDL peak particle diameter measurement
EFO:0007678	total fat intake measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536602	Amaurosis congenita of Leber, type 5 (supp.)

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
sodium arsenite	decreases expression, increases expression	3
Nickel	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
perfluorooctanoic acid	increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	increases expression	1
Benzene	decreases expression	1
Benzoates	increases expression	1
Cadmium	increases abundance, increases expression	1
Diethylstilbestrol	increases expression	1
Fenofibrate	increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05616793	PHASE1/PHASE2	RECRUITING	Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients