SH3GLB1

Summary

SH3GLB1 (SH3 domain containing GRB2 like, endophilin B1, HGNC:10833) is a protein-coding gene on chromosome 1p22.3, encoding Endophilin-B1 (Q9Y371). May be required for normal outer mitochondrial membrane dynamics.

This gene encodes a SRC homology 3 domain-containing protein. The encoded protein interacts with the proapoptotic member of the Bcl-2 family, Bcl-2-associated X protein (Bax) and may be involved in regulating apoptotic signaling pathways. This protein may also be involved in maintaining mitochondrial morphology. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 51100 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_016009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10833
Approved symbol	SH3GLB1
Name	SH3 domain containing GRB2 like, endophilin B1
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-61, KIAA0491, Bif-1, PPP1R70
Ensembl gene	ENSG00000097033
Ensembl biotype	protein_coding
OMIM	609287
Entrez	51100

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 retained_intron

ENST00000370558, ENST00000482504, ENST00000535010, ENST00000602603, ENST00000616170, ENST00000705519, ENST00000897334, ENST00000897335, ENST00000897336, ENST00000897337, ENST00000897338, ENST00000897339, ENST00000961404, ENST00000961405

RefSeq mRNA: 5 — MANE Select: NM_016009 NM_001206651, NM_001206652, NM_001206653, NM_001410824, NM_016009

CCDS: CCDS55612, CCDS55613, CCDS710, CCDS72819, CCDS90998

Canonical transcript exons

ENST00000370558 — 9 exons

Exon	Start	End
ENSE00000776117	86715724	86715865
ENSE00000776119	86722540	86722673
ENSE00000776120	86724313	86724405
ENSE00000776121	86734602	86734691
ENSE00001013170	86704576	86704971
ENSE00001453014	86743128	86748184
ENSE00003326584	86742208	86742436
ENSE00003660538	86735079	86735179
ENSE00003683646	86719507	86719635

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.8230 / max 952.8712, expressed in 1825 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3875	68.2629	1820
3870	12.8338	1784
3869	10.6790	1785
3873	1.5043	907
3876	1.3237	864
3868	1.2347	807
3877	0.9025	575
3871	0.6788	430
3874	0.5269	299
3878	0.4725	227

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	98.38	gold quality
deltoid	UBERON:0001476	98.23	gold quality
heart right ventricle	UBERON:0002080	97.83	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.80	gold quality
gastrocnemius	UBERON:0001388	97.70	gold quality
diaphragm	UBERON:0001103	97.68	gold quality
oocyte	CL:0000023	97.65	gold quality
skeletal muscle tissue	UBERON:0001134	97.56	gold quality
biceps brachii	UBERON:0001507	97.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.55	gold quality
islet of Langerhans	UBERON:0000006	97.54	gold quality
muscle of leg	UBERON:0001383	97.54	gold quality
muscle organ	UBERON:0001630	97.54	gold quality
quadriceps femoris	UBERON:0001377	97.53	gold quality
gluteal muscle	UBERON:0002000	97.51	gold quality
triceps brachii	UBERON:0001509	97.47	gold quality
vastus lateralis	UBERON:0001379	97.46	gold quality
adult organism	UBERON:0007023	97.14	gold quality
muscle tissue	UBERON:0002385	96.99	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.89	gold quality
adipose tissue	UBERON:0001013	96.87	gold quality
omental fat pad	UBERON:0010414	96.84	gold quality
peritoneum	UBERON:0002358	96.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.81	gold quality
left testis	UBERON:0004533	96.74	gold quality
skin of hip	UBERON:0001554	96.73	gold quality
connective tissue	UBERON:0002384	96.73	gold quality
secondary oocyte	CL:0000655	96.61	gold quality
rectum	UBERON:0001052	96.50	gold quality
right testis	UBERON:0004534	96.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8530	no	781.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

231 targeting SH3GLB1, 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-6740-5P	100.00	65.64	932
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-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669

Literature-anchored findings (GeneRIF, showing 27)

• Double knockdown of endophilin B1 and Drp1 leads to a mitochondrial phenotype identical to that of the Drp1 single knockdown, a result consistent with Drp1 acting upstream of endophilin B1 in the maintenance of morphological dynamics of mitochondria. (PMID:15452144)
• Bif-1 is an important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator, and loss of this proapoptotic molecule may contribute to tumorigenesis. (PMID:16227588)
• BAR domain of endophilin-A1 drives membrane curvature by coordinate action of the crescent’s scaffold mechanism and the ridge’s membrane insertion in addition to membrane binding via amino-terminal amphipathic helix. (PMID:16763557)
• The decreased expression of Bif-1 in malignant gastric epithelial cells compared with the normal mucosal cells suggests that loss of Bif-1 expression may play a role in gastric tumorigenesis, possibly by inhibiting the apoptosis mediated by Bif-1. (PMID:16916719)
• Src phosphorylation of Bif-1 suppresses the interaction between Bif-1 and Bax, resulting in the inhibition of Bax activation during anoikis. (PMID:18474606)
• Bif-1 expression might play a role in tumorigenesis in both urinary bladder (UB) and gallbladder (GB) cancer (PMID:18752120)
• The loss of Bif-1 expression in a subset of prostate cancer samples is in agreement with the proapoptotic function of Bif-1. (PMID:18824435)
• down-regulation of Bif-1 during the transition from normal colorectal mucosa to colorectal adenocarcinoma (PMID:18833585)
• DLP1 also caused global morphological changes in mitochondrial outer membrane-like liposomes, but DLP1 did not stimulate BAX-permeabilizing function in the absence or presence of Bif-1. (PMID:19074440)
• upregulation of Bif-1 could in part be responsible for tumorigenesis in cutaneous Merkel cell carcinoma (PMID:19125733)
• Deregulation of Bif-1-related cell death is dependent not on Bif-1 mutation but on other mechanisms. (PMID:19132989)
• Bax activates endophilin B1 oligomerization and lipid membrane vesiculation (PMID:19805544)
• GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagic response and cell death. (PMID:20159967)
• These findings suggest that Bif-1 acts as a critical regulator of Atg9 puncta formation presumably by mediating Golgi fission for autophagosome biogenesis during starvation. (PMID:21068542)
• The expression of Bif-1 is downregulated in a subset of pancreatic ductal adenocarcinoma. This novel finding is in agreement with the tumor suppressor function of Bif-1. (PMID:21283040)
• these data suggest a novel function for Bif-1 as a suppressor of breast cancer cell migration by promoting EGFR degradation through the regulation of endosome maturation (PMID:22785202)
• Data suggest that activated autophagy is associated with the progression of pancreatic ductal adenocarcinoma and that the overexpression of autophagy-related proteins Atg5, Ambra1, beclin-1, LC3B and Bif-1 is significantly correlated with poor outcome. (PMID:23429496)
• these data reveal an Irgm1-dependent mechanism that promotes the tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy (PMID:25619828)
• Our findings suggest that endophilin-B1 is a key mediator of a feed-forward mechanism of Alzheimer’s disease pathogenesis (PMID:25981964)
• 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)
• endophilin B1 participates in dynamin 2-dependent formation of a population of transport vesicles distinct from those generated by A-type endophilins (PMID:27508440)
• endophilin B1 mediated the biological function of EGFR in cancer cell proliferation through regulating the EGFR endocytic trafficking and downstream signaling. (PMID:27609472)
• Bif-1 is involved in prostate cancer tumorigenesis and acts as a suppressor in prostate cancer progression. (PMID:27748942)
• during cell stress, Bif-1 regulates mitochondrial inner membrane by interacting with prohibitin-2 to disrupt prohibitin complexes and induce OPA1 proteolysis and inactivation. (PMID:31126972)
• BIF-1 inhibits both mitochondrial and glycolytic ATP production: its downregulation promotes melanoma growth. (PMID:32493957)
• Amphipathic Motifs Regulate N-BAR Protein Endophilin B1 Auto-inhibition and Drive Membrane Remodeling. (PMID:33086035)
• Loss of Concurrent Regulation of the Expression of BIF-1, BAX, and Beclin-1 in Primary and Metastatic Melanoma. (PMID:33202207)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3glb1b	ENSDARG00000010956
danio_rerio	sh3glb1a	ENSDARG00000045294
mus_musculus	Sh3glb1	ENSMUSG00000037062
rattus_norvegicus	Sh3glb1	ENSRNOG00000012957
drosophila_melanogaster	Dlish	FBGN0034264
caenorhabditis_elegans		WBGENE00012891
caenorhabditis_elegans		WBGENE00015128

Paralogs (12): SORBS1 (ENSG00000095637), NCF4 (ENSG00000100365), SH3GL2 (ENSG00000107295), SH3D19 (ENSG00000109686), SORBS3 (ENSG00000120896), SH3GL3 (ENSG00000140600), SH3GL1 (ENSG00000141985), SH3GLB2 (ENSG00000148341), SH3RF1 (ENSG00000154447), SORBS2 (ENSG00000154556), SH3RF2 (ENSG00000156463), SH3RF3 (ENSG00000172985)

Protein

Protein identifiers

Endophilin-B1 — Q9Y371 (reviewed: Q9Y371)

Alternative names: Bax-interacting factor 1, SH3 domain-containing GRB2-like protein B1

All UniProt accessions (4): Q9Y371, A0A087WW40, A0A140VJU5, A0A994J549

UniProt curated annotations — full annotation on UniProt →

Function. May be required for normal outer mitochondrial membrane dynamics. Required for coatomer-mediated retrograde transport in certain cells. May recruit other proteins to membranes with high curvature. May promote membrane fusion. Involved in activation of caspase-dependent apoptosis by promoting BAX/BAK1 activation. Isoform 1 acts proapoptotic in fibroblasts. Involved in caspase-independent apoptosis during nutrition starvation and involved in the regulation of autophagy. Activates lipid kinase activity of PIK3C3 during autophagy probably by associating with the PI3K complex II (PI3KC3-C2). Associated with PI3KC3-C2 during autophagy may regulate the trafficking of ATG9A from the Golgi complex to the peripheral cytoplasm for the formation of autophagosomes by inducing Golgi membrane tubulation and fragmentation. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2. Isoform 2 acts antiapoptotic in neuronal cells; involved in maintenance of mitochondrial morphology and promotes neuronal viability.

Subunit / interactions. Homodimer, and heterodimer with SH3GLB2. Binds BAX; induction of apoptosis augments BAX binding. Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1. Interacts with UVRAG; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex II (PI3KC3-C2).

Subcellular location. Cytoplasm. Golgi apparatus membrane. Mitochondrion outer membrane. Cytoplasmic vesicle. Autophagosome membrane. Midbody.

Tissue specificity. Highly expressed in heart, skeletal muscle, kidney and placenta. Detected at lower levels in brain, colon, thymus, spleen, liver, small intestine, lung and peripheral blood leukocytes.

Post-translational modifications. Phosphorylated at Thr-145 by CDK5; this phosphorylation is required for autophagy induction in starved neurons and facilitates homodimerization.

Domain organisation. An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The SH3 domain is required and sufficient for the interaction with UVRAG.

Miscellaneous. HeLa cells lacking SH3GLB1 show dissociation of outer and inner mitochondrial membrane as well as abnormal mitochondrial morphology. Cells overexpressing SH3GLB1 lacking an N-terminal amphipathic helix show a similar phenotype. SH3GLB1 binds liposomes and induces formation of tubules from liposomes. SH3GLB1 lacking the N-terminal amphipathic helix fails to induce liposome tubulation.

Similarity. Belongs to the endophilin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y371-1	1	yes
Q9Y371-2	2
Q9Y371-3	3

RefSeq proteins (5): NP_001193580, NP_001193581, NP_001193582, NP_001397753, NP_057093* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR028503	SH3GLB_SH3	Domain
IPR035695	SH3GLB1_BAR	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR050384	Endophilin_SH3RF	Family

Pfam: PF03114, PF14604

UniProt features (23 total): helix 8, mutagenesis site 3, domain 2, strand 2, region of interest 2, modified residue 2, splice variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9G2U	ELECTRON MICROSCOPY	3.45
9G2W	ELECTRON MICROSCOPY	3.6
9G2R	ELECTRON MICROSCOPY	3.88
6UP6	ELECTRON MICROSCOPY	9
6UPN	ELECTRON MICROSCOPY	10

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y371-F1	84.88	0.65

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 (2): 1, 145

Mutagenesis-validated functional residues (3):

Position	Phenotype
8	abolishes interaction with bax.
145	reduced cdk5-mediated phosphorylation and impaired dimerization.
145	spontaneous dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 298 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GCM_MAP4K4, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (21): phosphatidic acid biosynthetic process (GO:0006654), autophagy (GO:0006914), apoptotic process (GO:0006915), positive regulation of autophagy (GO:0010508), regulation of macroautophagy (GO:0016241), positive regulation of protein-containing complex assembly (GO:0031334), regulation of protein stability (GO:0031647), regulation of cytokinesis (GO:0032465), receptor catabolic process (GO:0032801), cellular response to amino acid starvation (GO:0034198), cellular response to glucose starvation (GO:0042149), autophagic cell death (GO:0048102), ‘de novo’ post-translational protein folding (GO:0051084), membrane organization (GO:0061024), membrane fission (GO:0090148), positive regulation of membrane tubulation (GO:1903527), protein localization to vacuolar membrane (GO:1903778), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), positive regulation of autophagosome assembly (GO:2000786), phospholipid biosynthetic process (GO:0008654), positive regulation of protein localization to mitochondrion (GO:1903749)

GO Molecular Function (8): fatty acid binding (GO:0005504), lysophosphatidic acid acyltransferase activity (GO:0042171), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), phosphatidylinositol 3-kinase activator activity (GO:0141038), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (12): Golgi membrane (GO:0000139), autophagosome membrane (GO:0000421), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), membrane (GO:0016020), nuclear body (GO:0016604), midbody (GO:0030496), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	4
programmed cell death	2
regulation of autophagy	2
macroautophagy	2
positive regulation of cellular component organization	2
cellular response to starvation	2
binding	2
intracellular membrane-bounded organelle	2
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
autophagy	1
positive regulation of catabolic process	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
protein-containing complex assembly	1
regulation of biological quality	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
macromolecule catabolic process	1
receptor metabolic process	1
response to amino acid starvation	1
‘de novo’ protein folding	1
cellular component organization	1
membrane organization	1
plasma membrane tubulation	1
regulation of membrane tubulation	1
protein localization to membrane	1
protein localization to vacuole	1
autophagosome assembly	1
positive regulation of macroautophagy	1
positive regulation of vacuole organization	1
positive regulation of organelle assembly	1
regulation of autophagosome assembly	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3GLB1	UVRAG	Q9P2Y5	996
SH3GLB1	BECN1	Q14457	993
SH3GLB1	AMBRA1	Q9C0C7	985
SH3GLB1	ATG14	Q6ZNE5	947
SH3GLB1	PIK3R4	Q99570	945
SH3GLB1	PIK3C3	Q8NEB9	880
SH3GLB1	IRGM	A1A4Y4	803
SH3GLB1	RUBCN	Q92622	761
SH3GLB1	BIN1	O00499	718
SH3GLB1	DNM1L	O00429	711
SH3GLB1	ATG10	Q9H0Y0	678
SH3GLB1	SYNJ1	O43426	653
SH3GLB1	MBOAT2	Q6ZWT7	648
SH3GLB1	MFN2	O95140	618
SH3GLB1	ATG5	Q9H1Y0	610

IntAct

582 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
UVRAG	BECN1	psi-mi:“MI:0914”(association)	0.970
PIK3C3	BECN1	psi-mi:“MI:0914”(association)	0.970
BECN1	PIK3C3	psi-mi:“MI:0915”(physical association)	0.970
COQ8A	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.810
SH3GLB1	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.800
TFIP11	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.780
SH3GLB1	TFIP11	psi-mi:“MI:0915”(physical association)	0.780
ZNF576	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.720
SH3GLB1	ZNF576	psi-mi:“MI:0915”(physical association)	0.720
SH3GLB1	C1D	psi-mi:“MI:0915”(physical association)	0.720
MAL2	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (173): SH3GLB1 (Two-hybrid), SH3GLB1 (Two-hybrid), SH3GLB1 (Two-hybrid), SH3GLB1 (Two-hybrid), SH3GLB2 (Two-hybrid), ZNF576 (Two-hybrid), CMTM5 (Two-hybrid), FUNDC1 (Two-hybrid), SH3GLB1 (Affinity Capture-MS), CCDC22 (Co-fractionation), COMMD3 (Co-fractionation), DSCR3 (Co-fractionation), FLAD1 (Co-fractionation), RPRD1A (Co-fractionation), UBE2I (Co-fractionation)

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

5 interactions.

A	Effect	B	Mechanism
SH3GLB1	up-regulates	CBL	binding
SH3GLB1	up-regulates	BAK1
SH3GLB1	up-regulates	BAX	binding
SH3GLB1	up-regulates	BECN1	binding
SH3GLB1	up-regulates	Endocytosis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1564 predictions. Top by Δscore:

Variant	Effect	Δscore
1:86715712:A:AG	acceptor_gain	1.0000
1:86715866:G:GG	donor_gain	1.0000
1:86719503:CTAG:C	acceptor_loss	1.0000
1:86719504:TA:T	acceptor_loss	1.0000
1:86719505:A:AG	acceptor_gain	1.0000
1:86719505:AGAT:A	acceptor_gain	1.0000
1:86719506:G:GT	acceptor_gain	1.0000
1:86719506:GA:G	acceptor_gain	1.0000
1:86719506:GAT:G	acceptor_gain	1.0000
1:86719506:GATG:G	acceptor_gain	1.0000
1:86719631:TTATG:T	donor_gain	1.0000
1:86719632:TATG:T	donor_gain	1.0000
1:86719632:TATGG:T	donor_loss	1.0000
1:86719634:TG:T	donor_gain	1.0000
1:86719635:GG:G	donor_gain	1.0000
1:86719636:G:GG	donor_gain	1.0000
1:86719636:GTAA:G	donor_loss	1.0000
1:86719637:TAAG:T	donor_loss	1.0000
1:86722534:TTGCA:T	acceptor_loss	1.0000
1:86722535:TGCA:T	acceptor_loss	1.0000
1:86722536:GCAGG:G	acceptor_loss	1.0000
1:86722537:CA:C	acceptor_loss	1.0000
1:86722538:A:AG	acceptor_gain	1.0000
1:86722538:A:AT	acceptor_loss	1.0000
1:86722538:AG:A	acceptor_gain	1.0000
1:86722539:G:GA	acceptor_gain	1.0000
1:86722539:GG:G	acceptor_gain	1.0000
1:86722539:GGT:G	acceptor_gain	1.0000
1:86722539:GGTA:G	acceptor_gain	1.0000
1:86722669:TTGCT:T	donor_gain	1.0000

AlphaMissense

2404 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:86704960:C:A	R21S	1.000
1:86704963:G:C	A22P	1.000
1:86704964:C:A	A22D	1.000
1:86719528:T:A	V79D	1.000
1:86719605:G:T	G105W	1.000
1:86719606:G:A	G105E	1.000
1:86722540:G:A	G115D	1.000
1:86722549:T:A	L118H	1.000
1:86722549:T:C	L118P	1.000
1:86722561:G:A	G122E	1.000
1:86724341:G:C	R169T	1.000
1:86724342:A:C	R169S	1.000
1:86724342:A:T	R169S	1.000
1:86724344:T:C	L170P	1.000
1:86734642:G:C	R204P	1.000
1:86734669:T:C	L213P	1.000
1:86735098:T:C	L227P	1.000
1:86735161:T:C	L248P	1.000
1:86742375:C:A	A310D	1.000
1:86742381:T:A	V312D	1.000
1:86742417:T:C	L324S	1.000
1:86742423:T:A	L326H	1.000
1:86742423:T:C	L326P	1.000
1:86743138:T:A	V334E	1.000
1:86743167:T:A	W344R	1.000
1:86743167:T:C	W344R	1.000
1:86743171:T:C	L345P	1.000
1:86743176:G:A	G347R	1.000
1:86743176:G:C	G347R	1.000
1:86743176:G:T	G347W	1.000

dbSNP variants (sampled 300 via entrez): RS1000017715 (1:86708680 A>G), RS1000033069 (1:86705504 G>C), RS1000066885 (1:86722011 T>C), RS1000104930 (1:86705829 A>G), RS1000167237 (1:86718619 A>G), RS1000179947 (1:86715333 A>G), RS1000198119 (1:86718850 G>A), RS1000227957 (1:86711533 A>T), RS1000234040 (1:86715567 CA>C,CAA), RS1000243504 (1:86746849 T>A,C), RS1000306998 (1:86711906 G>C,T), RS1000457492 (1:86746641 G>A,T), RS1000493803 (1:86728039 A>G,T), RS1000512651 (1:86716920 A>C,G), RS1000543598 (1:86717253 A>T)

Disease associations

OMIM: gene MIM:609287 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, increases expression	4
bisphenol A	decreases expression, increases expression	2
Leflunomide	increases expression	2
Acetaminophen	increases expression	2
Vehicle Emissions	affects expression, increases reaction, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	increases expression	1
nefazodone	affects cotreatment, increases expression	1
deguelin	increases expression	1
K 7174	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Atazanavir Sulfate	affects cotreatment, increases expression	1
Sunitinib	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK96	HAP1 SH3GLB1 (-) 1	Cancer cell line	Male
CVCL_TK97	HAP1 SH3GLB1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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