SH3GLB2

Summary

SH3GLB2 (SH3 domain containing GRB2 like, endophilin B2, HGNC:10834) is a protein-coding gene on chromosome 9q34.11, encoding Endophilin-B2 (Q9NR46).

Enables identical protein binding activity. Predicted to be involved in membrane organization and postsynaptic neurotransmitter receptor internalization. Located in cytosol and nucleoplasm.

Source: NCBI Gene 56904 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_020145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10834
Approved symbol	SH3GLB2
Name	SH3 domain containing GRB2 like, endophilin B2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1848
Ensembl gene	ENSG00000148341
Ensembl biotype	protein_coding
OMIM	609288
Entrez	56904

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 23 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000372554, ENST00000372559, ENST00000372564, ENST00000416230, ENST00000416629, ENST00000417224, ENST00000425236, ENST00000455407, ENST00000461811, ENST00000477165, ENST00000479237, ENST00000483980, ENST00000935419, ENST00000935420, ENST00000935421, ENST00000935422, ENST00000935423, ENST00000940981, ENST00000940982, ENST00000940983, ENST00000940984, ENST00000940985, ENST00000940986, ENST00000940987, ENST00000940988, ENST00000940989, ENST00000940990, ENST00000940991, ENST00000940992, ENST00000940993

RefSeq mRNA: 6 — MANE Select: NM_020145 NM_001287045, NM_001287046, NM_001369913, NM_001369914, NM_001369915, NM_020145

CCDS: CCDS6916, CCDS69680

Canonical transcript exons

ENST00000372564 — 11 exons

Exon	Start	End
ENSE00001458108	129028092	129028331
ENSE00001876139	129007036	129008791
ENSE00003482848	129010670	129010693
ENSE00003490503	129012236	129012298
ENSE00003514066	129009106	129009346
ENSE00003515331	129014771	129014904
ENSE00003527976	129021091	129021219
ENSE00003574768	129009771	129009871
ENSE00003620630	129010120	129010209
ENSE00003674049	129022282	129022423
ENSE00003676653	129014411	129014503

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.4209 / max 208.2473, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102719	22.4146	1814
102718	1.0063	374

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	98.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.70	gold quality
right frontal lobe	UBERON:0002810	98.68	gold quality
skin of abdomen	UBERON:0001416	98.62	gold quality
skin of leg	UBERON:0001511	98.61	gold quality
anterior cingulate cortex	UBERON:0009835	98.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.31	gold quality
lower esophagus mucosa	UBERON:0035834	98.25	gold quality
cingulate cortex	UBERON:0003027	98.23	gold quality
prefrontal cortex	UBERON:0000451	98.22	gold quality
metanephros cortex	UBERON:0010533	98.18	gold quality
pituitary gland	UBERON:0000007	98.13	gold quality
body of stomach	UBERON:0001161	98.11	gold quality
right uterine tube	UBERON:0001302	98.01	gold quality
tibial nerve	UBERON:0001323	98.00	gold quality
body of pancreas	UBERON:0001150	97.96	gold quality
minor salivary gland	UBERON:0001830	97.94	gold quality
cerebellar hemisphere	UBERON:0002245	97.93	gold quality
cerebellar cortex	UBERON:0002129	97.88	gold quality
transverse colon	UBERON:0001157	97.57	gold quality
right lobe of thyroid gland	UBERON:0001119	97.53	gold quality
right adrenal gland cortex	UBERON:0035827	97.53	gold quality
mucosa of transverse colon	UBERON:0004991	97.52	gold quality
esophagus mucosa	UBERON:0002469	97.47	gold quality
endocervix	UBERON:0000458	97.43	gold quality
left uterine tube	UBERON:0001303	97.43	gold quality
right adrenal gland	UBERON:0001233	97.42	gold quality
left lobe of thyroid gland	UBERON:0001120	97.40	gold quality
mucosa of stomach	UBERON:0001199	97.40	gold quality
ectocervix	UBERON:0012249	97.39	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	66.14
E-ANND-3	yes	11.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting SH3GLB2, 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-4692	100.00	67.32	2066
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013

Literature-anchored findings (GeneRIF, showing 4)

• identified a nonmutated HLA-A2-binding epitope in the human ortholog SH3GLB2, which primed T cells from healthy HLA-A2(+) individuals (PMID:18303116)
• the potential importance of the endophilin B2-plectin complex in the biological functions depending on nuclear migration and positioning. (PMID:23921385)
• Here the authors report that Endophilin B2, similarly to Endophilin B1, plays an indispensable role in mitochondria sequestration and inner mitochondrial membrane (IMM) protein degradation during mitophagy. (PMID:27112121)
• Data (including data from studies in knockout mice) suggest that SH3GLB2 regulates trafficking of endocytic vesicles and autophagosomes to late endosomes or lysosomes; despite having an intracellular localization and tissue distribution similar to endophilin B1, endophilin B2 is dispensable for mitochondrial apoptosis. (PMID:28455444)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3glb2a	ENSDARG00000008983
danio_rerio	sh3glb2b	ENSDARG00000035470
mus_musculus	Sh3glb2	ENSMUSG00000026860
rattus_norvegicus	Sh3glb2	ENSRNOG00000017295
drosophila_melanogaster	Dlish	FBGN0034264
caenorhabditis_elegans		WBGENE00012891
caenorhabditis_elegans		WBGENE00015128

Paralogs (12): SORBS1 (ENSG00000095637), SH3GLB1 (ENSG00000097033), NCF4 (ENSG00000100365), SH3GL2 (ENSG00000107295), SH3D19 (ENSG00000109686), SORBS3 (ENSG00000120896), SH3GL3 (ENSG00000140600), SH3GL1 (ENSG00000141985), SH3RF1 (ENSG00000154447), SORBS2 (ENSG00000154556), SH3RF2 (ENSG00000156463), SH3RF3 (ENSG00000172985)

Protein

Protein identifiers

Endophilin-B2 — Q9NR46 (reviewed: Q9NR46)

Alternative names: SH3 domain-containing GRB2-like protein B2

All UniProt accessions (6): Q9NR46, B7ZC38, B7ZC39, F8WFB9, G5E9J1, H7C1Z6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer, and heterodimer with SH3GLB1.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in skeletal muscle, adipocyte, brain, lung, colon and mammary gland.

Similarity. Belongs to the endophilin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR46-1	1	yes
Q9NR46-2	2

RefSeq proteins (6): NP_001273974, NP_001273975, NP_001356842, NP_001356843, NP_001356844, NP_064530* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR035640	Endophilin_B2_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR050384	Endophilin_SH3RF	Family

Pfam: PF03114, PF14604

UniProt features (13 total): modified residue 3, domain 2, splice variant 2, sequence variant 2, coiled-coil region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR46-F1	79.35	0.51

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 (3): 1, 10, 395

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, WANG_RECURRENT_LIVER_CANCER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GGGTGGRR_PAX4_03, RICKMAN_METASTASIS_DN, GATA3_01, RFX1_02, GOBP_MEMBRANE_ORGANIZATION, KEGG_ENDOCYTOSIS, GOBP_IMPORT_INTO_CELL, CTAWWWATA_RSRFC4_Q2

GO Biological Process (1): membrane organization (GO:0061024)

GO Molecular Function (3): identical protein binding (GO:0042802), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular component organization	1
protein binding	1
cell adhesion molecule binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3GLB2	SH3KBP1	Q96B97	734
SH3GLB2	BIN1	O00499	682
SH3GLB2	MBOAT2	Q6ZWT7	648
SH3GLB2	OPHN1	O60890	622
SH3GLB2	DNM1L	O00429	592
SH3GLB2	SYNJ1	O43426	590
SH3GLB2	UXT	Q9UBK9	581
SH3GLB2	SH3GLB1	Q9Y371	579
SH3GLB2	UVRAG	Q9P2Y5	497
SH3GLB2	TRAPPC6A	O75865	494
SH3GLB2	TTC7B	Q86TV6	461
SH3GLB2	MYO18A	O95411	448
SH3GLB2	HYCC1	Q9BYI3	431
SH3GLB2	ERBB4	Q15303	425
SH3GLB2	STARD8	Q92502	425

IntAct

135 interactions, top by confidence:

A	B	Type	Score
SH3GLB1	SH3GLB2	psi-mi:“MI:0915”(physical association)	0.970
SH3GLB2	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.970
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
SH3GLB2	MAGEA1	psi-mi:“MI:0915”(physical association)	0.620
SH3GLB2	SH3GLB2	psi-mi:“MI:0915”(physical association)	0.620
MAGEA1	SH3GLB2	psi-mi:“MI:0915”(physical association)	0.620
STK4	STRN	psi-mi:“MI:2364”(proximity)	0.610
SH3GLB2	RRD1	psi-mi:“MI:0915”(physical association)	0.560
EFHC1	SH3GLB2	psi-mi:“MI:0915”(physical association)	0.560
LGALS14	SH3GLB2	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB2	PICK1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (131): SH3GLB2 (Two-hybrid), SH3GLB2 (Two-hybrid), CCDC158 (Two-hybrid), SH3GLB2 (Proximity Label-MS), SH3GLB2 (Proximity Label-MS), RHOA (Reconstituted Complex), RHOA (Affinity Capture-Western), SH3GLB2 (Two-hybrid), SH3GLB2 (Proximity Label-MS), SH3GLB2 (Two-hybrid), SH3GLB1 (Two-hybrid), SH3GLB2 (Two-hybrid), SH3GLB2 (Two-hybrid), SH3GLB2 (Two-hybrid), SH3GLB2 (Two-hybrid)

ESM2 similar proteins: A1XBS5, B0S6J3, D4A208, O35180, O35964, O43295, O75044, P0DJJ0, P0DMP2, P25343, Q08DK5, Q15057, Q1LU86, Q1RMK1, Q2VR06, Q32LM0, Q3SZG6, Q3V2J0, Q5AFE4, Q5FVC7, Q5PPJ9, Q5PPZ5, Q5R8P5, Q5ZIR1, Q5ZJ81, Q5ZK62, Q62419, Q62421, Q68FW8, Q6AYE2, Q6GN09, Q6IVG4, Q6ZQK5, Q6ZTR7, Q7Z6B7, Q812A2, Q8AXU9, Q8BP22, Q8I190, Q8I1C0

Diamond homologs: Q08DK5, Q32LM0, Q5PPJ9, Q5R8P5, Q5ZIR1, Q5ZJ81, Q6AYE2, Q8R3V5, Q9JK48, Q9NR46, Q9Y371, Q555L8, P10569, P34109, P97814, O43586

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SH3GLB2	up-regulates	Endocytosis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Autophagy	5	14.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2072 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129008687:G:C	donor_gain	1.0000
9:129009130:A:AC	donor_gain	1.0000
9:129009131:C:CC	donor_gain	1.0000
9:129009131:CTG:C	donor_gain	1.0000
9:129009347:C:CC	acceptor_gain	1.0000
9:129009765:CCGCA:C	donor_loss	1.0000
9:129009766:CGCA:C	donor_loss	1.0000
9:129009767:GCAC:G	donor_loss	1.0000
9:129009768:CA:C	donor_loss	1.0000
9:129009770:CC:C	donor_loss	1.0000
9:129009778:G:C	donor_gain	1.0000
9:129009867:TTCAC:T	acceptor_gain	1.0000
9:129009868:TCAC:T	acceptor_gain	1.0000
9:129009869:CAC:C	acceptor_gain	1.0000
9:129009869:CACC:C	acceptor_gain	1.0000
9:129009870:AC:A	acceptor_gain	1.0000
9:129009870:ACCT:A	acceptor_loss	1.0000
9:129009871:CC:C	acceptor_gain	1.0000
9:129009872:C:CC	acceptor_gain	1.0000
9:129009875:C:CT	acceptor_gain	1.0000
9:129009876:G:T	acceptor_gain	1.0000
9:129010118:A:AC	donor_gain	1.0000
9:129010119:C:CC	donor_gain	1.0000
9:129014406:CCTA:C	donor_loss	1.0000
9:129014407:CTAC:C	donor_loss	1.0000
9:129014409:A:AC	donor_gain	1.0000
9:129014409:ACCGT:A	donor_loss	1.0000
9:129014410:C:CC	donor_gain	1.0000
9:129014410:C:CG	donor_loss	1.0000
9:129014504:C:CC	acceptor_gain	1.0000

AlphaMissense

2568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129008700:A:G	L391S	0.999
9:129008715:A:T	V386D	0.999
9:129008742:C:T	G377D	0.999
9:129008748:A:G	L375P	0.999
9:129008781:A:T	V364D	0.999
9:129008700:A:C	L391W	0.998
9:129008704:A:C	Y390D	0.998
9:129008712:G:T	P387H	0.998
9:129008722:C:G	G384R	0.998
9:129008752:A:G	W374R	0.998
9:129008752:A:T	W374R	0.998
9:129008787:A:T	I362N	0.998
9:129009125:A:G	L354P	0.998
9:129014472:A:G	L167P	0.998
9:129014487:A:G	L162P	0.998
9:129014895:A:G	L115P	0.998
9:129008713:G:A	P387S	0.997
9:129008713:G:T	P387T	0.997
9:129008721:C:A	G384V	0.997
9:129008721:C:T	G384D	0.997
9:129008787:A:C	I362S	0.997
9:129009119:A:G	L356P	0.997
9:129009161:A:T	V342E	0.997
9:129009167:G:T	A340D	0.997
9:129014475:C:G	R166P	0.997
9:129028099:G:T	A19E	0.997
9:129028100:C:G	A19P	0.997
9:129008722:C:A	G384C	0.996
9:129008743:C:G	G377R	0.996
9:129008750:C:A	W374C	0.996

dbSNP variants (sampled 300 via entrez): RS1000337231 (9:129013580 T>C), RS1000369878 (9:129013743 C>A,G,T), RS1000559114 (9:129011454 C>T), RS1000559564 (9:129007405 G>T), RS1000580362 (9:129023377 G>C), RS1000629591 (9:129008449 G>A,T), RS1000673438 (9:129012296 C>T), RS1000960869 (9:129018568 C>G), RS1000997669 (9:129017819 A>C,G), RS1001113974 (9:129023966 C>T), RS1001164057 (9:129012591 G>A), RS1001234374 (9:129024662 A>G), RS1001510641 (9:129012354 T>A), RS1001524172 (9:129012948 G>A,T), RS1001556602 (9:129013257 G>A,C)

Disease associations

OMIM: gene MIM:609288 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006879_1	Blood metabolite levels	1.000000e-09
GCST006879_18	Blood metabolite levels	3.000000e-43
GCST006879_19	Blood metabolite levels	4.000000e-83
GCST006879_2	Blood metabolite levels	2.000000e-12
GCST006879_20	Blood metabolite levels	5.000000e-12
GCST006879_21	Blood metabolite levels	2.000000e-22
GCST006879_22	Blood metabolite levels	2.000000e-20
GCST012353_3	Serum metabolite concentrations in chronic kidney disease	2.000000e-12
GCST012353_36	Serum metabolite concentrations in chronic kidney disease	2.000000e-42

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Furaldehyde	affects localization, increases expression, decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Mercury	increases expression	1
Methotrexate	affects response to substance	1
Naled	affects expression	1
Potassium Dichromate	increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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