SORBS1

Summary

SORBS1 (sorbin and SH3 domain containing 1, HGNC:14565) is a protein-coding gene on chromosome 10q24.1, encoding Sorbin and SH3 domain-containing protein 1 (Q9BX66). Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor.

This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10580 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 255 total
• Druggable target: yes
• MANE Select transcript: NM_001034954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14565
Approved symbol	SORBS1
Name	sorbin and SH3 domain containing 1
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12406, CAP, sh3p12, ponsin, KIAA1296
Ensembl gene	ENSG00000095637
Ensembl biotype	protein_coding
OMIM	605264
Entrez	10580

Gene structure

Transcript identifiers

Ensembl transcripts: 223 — 219 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000277982, ENST00000306402, ENST00000354106, ENST00000361941, ENST00000371227, ENST00000371228, ENST00000371239, ENST00000371241, ENST00000371245, ENST00000371246, ENST00000371247, ENST00000371249, ENST00000465489, ENST00000472854, ENST00000474353, ENST00000482068, ENST00000486141, ENST00000492542, ENST00000607232, ENST00000634504, ENST00000647619, ENST00000649575, ENST00000649911, ENST00000901915, ENST00000901916, ENST00000901917, ENST00000901918, ENST00000901919, ENST00000901920, ENST00000901921, ENST00000901922, ENST00000901923, ENST00000901924, ENST00000901925, ENST00000901926, ENST00000901927, ENST00000901928, ENST00000901929, ENST00000901930, ENST00000901931, ENST00000901932, ENST00000901933, ENST00000901934, ENST00000901935, ENST00000901936, ENST00000901937, ENST00000901938, ENST00000901939, ENST00000901940, ENST00000901941, ENST00000901942, ENST00000901943, ENST00000901944, ENST00000901945, ENST00000901946, ENST00000901947, ENST00000901948, ENST00000901949, ENST00000901950, ENST00000901951, ENST00000901952, ENST00000901953, ENST00000901954, ENST00000901955, ENST00000901956, ENST00000901957, ENST00000901958, ENST00000901959, ENST00000901960, ENST00000901961, ENST00000901962, ENST00000901963, ENST00000901964, ENST00000901965, ENST00000901966, ENST00000901967, ENST00000901968, ENST00000901969, ENST00000901970, ENST00000901971, ENST00000901972, ENST00000901973, ENST00000901974, ENST00000901975, ENST00000901976, ENST00000901977, ENST00000901978, ENST00000901979, ENST00000901980, ENST00000901981, ENST00000901982, ENST00000901983, ENST00000901984, ENST00000901985, ENST00000901986, ENST00000901987, ENST00000901988, ENST00000901989, ENST00000901990, ENST00000901991, ENST00000901992, ENST00000901993, ENST00000901994, ENST00000901995, ENST00000901996, ENST00000901997, ENST00000901998, ENST00000901999, ENST00000902000, ENST00000902001, ENST00000902002, ENST00000902003, ENST00000902004, ENST00000902005, ENST00000902006, ENST00000902007, ENST00000902008, ENST00000902009, ENST00000902010, ENST00000902011, ENST00000902012, ENST00000902013, ENST00000902014, ENST00000902015, ENST00000902016, ENST00000902017, ENST00000902018, ENST00000902019, ENST00000902020, ENST00000902021, ENST00000902022, ENST00000902023, ENST00000902024, ENST00000902025, ENST00000902026, ENST00000902027, ENST00000902028, ENST00000902029, ENST00000902030, ENST00000902031, ENST00000902032, ENST00000902033, ENST00000902034, ENST00000902035, ENST00000902036, ENST00000902037, ENST00000902038, ENST00000902039, ENST00000902040, ENST00000902041, ENST00000902042, ENST00000902043, ENST00000902044, ENST00000902045, ENST00000902046, ENST00000902047, ENST00000902048, ENST00000902049, ENST00000902050, ENST00000902051, ENST00000902052, ENST00000902053, ENST00000902054, ENST00000902055, ENST00000902056, ENST00000902057, ENST00000902058, ENST00000902059, ENST00000902060, ENST00000902061, ENST00000902062, ENST00000902063, ENST00000902064, ENST00000902065, ENST00000902066, ENST00000902067, ENST00000902068, ENST00000902069, ENST00000902070, ENST00000902071, ENST00000902072, ENST00000902073, ENST00000902074, ENST00000902075, ENST00000919475, ENST00000919476, ENST00000919477, ENST00000919478, ENST00000919479, ENST00000919480, ENST00000919481, ENST00000919482, ENST00000919483, ENST00000919484, ENST00000919485, ENST00000919486, ENST00000919487, ENST00000919488, ENST00000919489, ENST00000919490, ENST00000919491, ENST00000919492, ENST00000919493, ENST00000919494, ENST00000954445, ENST00000954446, ENST00000954447, ENST00000954448, ENST00000954449, ENST00000954450, ENST00000954451, ENST00000954452, ENST00000954453, ENST00000954454, ENST00000954455, ENST00000954456, ENST00000954457, ENST00000954458, ENST00000954459, ENST00000954460, ENST00000954461, ENST00000954462, ENST00000954463

RefSeq mRNA: 48 — MANE Select: NM_001034954 NM_001034954, NM_001034955, NM_001034956, NM_001034957, NM_001290294, NM_001290295, NM_001290296, NM_001290297, NM_001290298, NM_001377197, NM_001377198, NM_001377199, NM_001377200, NM_001377201, NM_001377202, NM_001377203, NM_001377204, NM_001377205, NM_001377206, NM_001377207, NM_001377208, NM_001377209, NM_001384447, NM_001384448, NM_001384449, NM_001384450, NM_001384451, NM_001384452, NM_001384453, NM_001384454, NM_001384455, NM_001384456, NM_001384457, NM_001384458, NM_001384459, NM_001384460, NM_001384461, NM_001384462, NM_001384463, NM_001384464, NM_001384465, NM_001419685, NM_001419702, NM_001419703, NM_001419704, NM_006434, NM_015385, NM_024991

CCDS: CCDS31252, CCDS31253, CCDS31254, CCDS31255, CCDS31256, CCDS73169, CCDS7442, CCDS76326, CCDS76327

Canonical transcript exons

ENST00000371247 — 33 exons

Exon	Start	End
ENSE00000716757	95395001	95395075
ENSE00000810934	95434622	95434717
ENSE00000987290	95341564	95341678
ENSE00000987291	95341285	95341410
ENSE00000987292	95339133	95339327
ENSE00000987296	95351209	95351376
ENSE00000987298	95394611	95394673
ENSE00000987299	95375973	95376056
ENSE00000987300	95371984	95372049
ENSE00000987301	95371326	95371427
ENSE00001122727	95422190	95422216
ENSE00001802906	95491035	95491120
ENSE00001889771	95311773	95315126
ENSE00003465280	95410633	95410777
ENSE00003467810	95421961	95422073
ENSE00003484232	95437490	95437555
ENSE00003505771	95357631	95357803
ENSE00003526966	95321963	95322021
ENSE00003544586	95384238	95384285
ENSE00003559691	95414494	95414862
ENSE00003566311	95381685	95381799
ENSE00003566406	95318320	95318432
ENSE00003574119	95383985	95384114
ENSE00003589094	95354882	95354967
ENSE00003618682	95432448	95432576
ENSE00003634616	95367650	95367699
ENSE00003668935	95406118	95406147
ENSE00003679289	95336521	95337294
ENSE00003683917	95346406	95346452
ENSE00003687064	95441126	95441180
ENSE00003694149	95397220	95397283
ENSE00003784430	95399017	95399189
ENSE00003919507	95561320	95561371

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6991 / max 1157.6201, expressed in 931 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110816	16.8727	862
110798	1.3979	199
110817	0.9884	359
110772	0.5433	159
110796	0.3815	104
110795	0.1653	86
110802	0.1089	40
110794	0.0870	38
110797	0.0709	42
110757	0.0479	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.75	gold quality
saphenous vein	UBERON:0007318	99.63	gold quality
left ventricle myocardium	UBERON:0006566	99.55	gold quality
cauda epididymis	UBERON:0004360	99.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.48	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.47	gold quality
mucosa of stomach	UBERON:0001199	99.46	gold quality
descending thoracic aorta	UBERON:0002345	99.46	gold quality
lower esophagus	UBERON:0013473	99.45	gold quality
popliteal artery	UBERON:0002250	99.44	gold quality
tibial artery	UBERON:0007610	99.44	gold quality
aorta	UBERON:0000947	99.41	gold quality
right coronary artery	UBERON:0001625	99.41	gold quality
heart right ventricle	UBERON:0002080	99.40	gold quality
artery	UBERON:0001637	99.39	gold quality
thoracic aorta	UBERON:0001515	99.37	gold quality
ascending aorta	UBERON:0001496	99.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.32	gold quality
myocardium	UBERON:0002349	99.29	gold quality
seminal vesicle	UBERON:0000998	99.26	gold quality
urethra	UBERON:0000057	99.15	gold quality
left coronary artery	UBERON:0001626	99.13	gold quality
coronary artery	UBERON:0001621	99.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.06	gold quality
colonic epithelium	UBERON:0000397	99.05	gold quality
sural nerve	UBERON:0015488	99.02	gold quality
trigeminal ganglion	UBERON:0001675	99.01	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.01	gold quality
cranial nerve II	UBERON:0000941	99.00	gold quality
peripheral nervous system	UBERON:0000010	98.99	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	6328.44
E-GEOD-180759	yes	3623.46
E-HCAD-35	yes	2349.90
E-HCAD-25	yes	2034.97
E-MTAB-10287	yes	38.51
E-CURD-119	yes	11.72
E-GEOD-84465	yes	11.05
E-GEOD-75367	no	523.54
E-MTAB-6058	no	49.48
E-MTAB-9543	no	2.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

206 targeting SORBS1, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 26)

• regulates cytoskeletal organization and signal transduction–review (PMID:12510380)
• preliminary results indicate the depot-specific differential expression of sorbin and SH3 domain-containing-1(SORBS1) in relation to body mass index (PMID:12690089)
• SORBS1 polymorphism does not play a major role in premature pubarche, hyperandrogenism, and/or polycystic ovary syndrome in children and adolescent girls. (PMID:12849814)
• A novel isoform was identified in a yeast two-hybrid screen for A-kinase anchoring proteins expressed in the heart. (PMID:15716063)
• Soluble intracellular domain of teneurin-1 binds to the cell membrane enriched in CAP/ponsin (PMID:15777793)
• analysis of paxillin and ponsin interaction in nascent costameres of muscle cells (PMID:17462669)
• AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population. (PMID:18394047)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• These results suggest that SORBS1 and GCK are susceptibility loci for hypertension in Japanese women and that WISP1 is such a locus in men. (PMID:19282865)
• Mutation of Tyr326 altered the function of CAP during cell spreading. (PMID:19891780)
• The novel ponsin isoform and its interaction with Nck1/2 provide exciting insight into the convergence of signalling pathways at the costameres, and its crucial role for skeletal muscle differentiation and re-generation. (PMID:20129698)
• a novel signaling network containing FRS2, CAP and flotillin-1 (PMID:22235335)
• Sequestration of the ponsin splice variant R85FL by the polyglutamine-expanded Atx7 in cell is mediated by the specific SH3C-PRR interaction, which is implicated in the pathogenesis of spinocerebellar ataxia 7. (PMID:23892081)
• Our NMR and ITC data indicate that the SH3a and SH3b domains of CAP simultaneously bind to a long proline-rich region of vinculin with different binding specificities (PMID:24878663)
• data suggest that SORBS1 might be a gene involved in diabetic nephropathy. (PMID:25476525)
• association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset of hypertension (PMID:26962801)
• SORBS1 suppresses tumor metastasis and improves the sensitivity of breast cancer cells to antineoplastic agents. (PMID:27791200)
• The SORBS1 GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test in Chinese patients. (PMID:30002559)
• SORBS1 serves a metastatic role via suppression of AHNAK in colorectal cancer cell lines. (PMID:32319594)
• Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis. (PMID:34409913)
• A variation in SORBS1 is associated with type 2 diabetes and high-density lipoprotein cholesterol in Chinese population. (PMID:35107206)
• MicroRNA miR-3646 promotes malignancy of lung adenocarcinoma cells by suppressing sorbin and SH3 domain-containing protein 1 via the c-Jun NH2-terminal kinase signaling pathway. (PMID:35196185)
• Down-regulation and clinical significance of Sorbin and SH3 domain-containing protein 1 in bladder cancer tissues. (PMID:36854874)
• MiR-223-3p increases resistance of colorectal cancer cells to 5-fluorouracil via targeting SORBS1. (PMID:37164919)
• Increased serum extrachromosomal circular DNA SORBS1[circle] level is associated with insulin resistance in patients with newly diagnosed type 2 diabetes mellitus. (PMID:38212723)
• circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA. (PMID:38915053)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sorbs1	ENSDARG00000103435
mus_musculus	Sorbs1	ENSMUSG00000025006
rattus_norvegicus	Sorbs1	ENSRNOG00000015658
drosophila_melanogaster	Dlish	FBGN0034264
caenorhabditis_elegans		WBGENE00012891
caenorhabditis_elegans		WBGENE00015128

Paralogs (12): SH3GLB1 (ENSG00000097033), 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

Sorbin and SH3 domain-containing protein 1 — Q9BX66 (reviewed: Q9BX66)

Alternative names: Ponsin, SH3 domain protein 5, SH3P12, c-Cbl-associated protein

All UniProt accessions (8): Q9BX66, A0A0U1RQI5, A0A3B3IRR9, A0A3B3IRW8, A0A3B3IT56, Q5T925, S4R303, S4R406

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions.

Subunit / interactions. Interacts (via third SH3 domain) with the Ten-1 ICD form of TENM1; the interaction induces the translocation of SORBS1 to the nucleus. Interacts with INSM1. Interacts with the long isoform of AFDN and with VCL. AFDN and VCL bind to SORBS1 in a competitive manner and do not form a ternary complex. Interacts with ABL1, CBL, CBLB and INPPL1/SHIP2 through the third SH3 domain. Interaction with ABL1 occurs only after insulin stimulation while this has no effect on the interaction with INPPL1. Interacts with the insulin receptor but dissociates from it following insulin stimulation. Also interacts with SCA7, PTK2/FAK1 and flotillin. Interacts (via SH3 domain 2) with PXN.

Subcellular location. Cell junction. Adherens junction. Cell membrane. Cytoplasm. Cytoskeleton. Focal adhesion. Nucleus. Nucleus matrix.

Tissue specificity. Detected in skeletal muscle (at protein level). Widely expressed with highest levels in heart and skeletal muscle.

Post-translational modifications. O-glycosylated.

Miscellaneous. Derived from mouse ortholog data.

Isoforms (12)

UniProt ID	Names	Canonical?
Q9BX66-1	1	yes
Q9BX66-2	2
Q9BX66-3	3
Q9BX66-4	4
Q9BX66-5	5
Q9BX66-6	6
Q9BX66-7	7
Q9BX66-8	8
Q9BX66-9	9
Q9BX66-10	10
Q9BX66-11	11
Q9BX66-12	12

RefSeq proteins (48): NP_001030126, NP_001030127, NP_001030128, NP_001030129, NP_001277223, NP_001277224, NP_001277225, NP_001277226, NP_001277227, NP_001364126, NP_001364127, NP_001364128, NP_001364129, NP_001364130, NP_001364131, NP_001364132, NP_001364133, NP_001364134, NP_001364135, NP_001364136, NP_001364137, NP_001364138, NP_001371376, NP_001371377, NP_001371378, NP_001371379, NP_001371380, NP_001371381, NP_001371382, NP_001371383, NP_001371384, NP_001371385, NP_001371386, NP_001371387, NP_001371388, NP_001371389, NP_001371390, NP_001371391, NP_001371392, NP_001371393, NP_001371394, NP_001406614, NP_001406631, NP_001406632, NP_001406633, NP_006425, NP_056200, NP_079267 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR003127	SoHo_dom	Domain
IPR035606	SORBS1_SH3	Domain
IPR035610	SORBS1_SH3_1	Domain
IPR035611	SORBS1_SH3_2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR050384	Endophilin_SH3RF	Family

Pfam: PF00018, PF02208, PF07653, PF14604

UniProt features (147 total): modified residue 43, sequence conflict 23, splice variant 21, strand 19, compositionally biased region 15, region of interest 11, sequence variant 6, domain 4, helix 2, turn 2, chain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2O9S	X-RAY DIFFRACTION	0.83
4LN2	X-RAY DIFFRACTION	1
4LNP	X-RAY DIFFRACTION	1.41
2O31	X-RAY DIFFRACTION	1.5
2O9V	X-RAY DIFFRACTION	1.63
2DL3	SOLUTION NMR
2ECZ	SOLUTION NMR
2LJ0	SOLUTION NMR
2LJ1	SOLUTION NMR
2MOX	SOLUTION NMR
2O2W	POWDER DIFFRACTION

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BX66-F1	47.88	0.11

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 (43): 105, 346, 603, 923, 137, 452, 765, 469, 114, 730, 146, 387, 700, 478, 735, 114, 1213, 82, 86, 89 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction
R-HSA-397014	Muscle contraction

MSigDB gene sets: 368 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, WWTAAGGC_UNKNOWN, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOLDRATH_IMMUNE_MEMORY, GOBP_FOCAL_ADHESION_ASSEMBLY, KENNY_CTNNB1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, AP4_Q6, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (11): cell-matrix adhesion (GO:0007160), insulin receptor signaling pathway (GO:0008286), cell-substrate adhesion (GO:0031589), cellular response to insulin stimulus (GO:0032869), stress fiber assembly (GO:0043149), positive regulation of glycogen biosynthetic process (GO:0045725), positive regulation of D-glucose import across plasma membrane (GO:0046326), positive regulation of insulin receptor signaling pathway (GO:0046628), positive regulation of lipid biosynthetic process (GO:0046889), focal adhesion assembly (GO:0048041), positive regulation of protein localization to plasma membrane (GO:1903078)

GO Molecular Function (5): actin binding (GO:0003779), insulin receptor binding (GO:0005158), cytoskeletal protein binding (GO:0008092), signaling receptor complex adaptor activity (GO:0030159), protein binding (GO:0005515)

GO Cellular Component (16): stress fiber (GO:0001725), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), zonula adherens (GO:0005915), focal adhesion (GO:0005925), nuclear matrix (GO:0016363), flotillin complex (GO:0016600), cell-substrate junction (GO:0030055), membrane raft (GO:0045121), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signaling receptor binding	2
cell-substrate adhesion	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
cell adhesion	1
response to insulin	1
cellular response to peptide hormone stimulus	1
contractile actin filament bundle assembly	1
actomyosin structure organization	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of glycogen metabolic process	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
lipid biosynthetic process	1
positive regulation of biosynthetic process	1
positive regulation of lipid metabolic process	1
regulation of lipid biosynthetic process	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
cytoskeletal protein binding	1
protein binding	1
signaling adaptor activity	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SORBS1	HLA-C	P04222	990
SORBS1	VCL	P18206	981
SORBS1	SPART	Q8N0X7	956
SORBS1	AFDN	P55196	944
SORBS1	CBL	P22681	930
SORBS1	TENM1	Q9UKZ4	913
SORBS1	TRIM45	Q9H8W5	908
SORBS1	KIR2DL1	P43626	874
SORBS1	INSM1	Q01101	844
SORBS1	ATXN7	O15265	823
SORBS1	KIR3DL3	Q8N743	822
SORBS1	KIR2DL3	P43628	814
SORBS1	FCHSD2	O94868	811
SORBS1	ATXN7L2	Q5T6C5	793
SORBS1	KIR3DL2	P43630	790

IntAct

107 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
SORBS1	ATXN7	psi-mi:“MI:0407”(direct interaction)	0.630
ATXN7	SORBS1	psi-mi:“MI:0407”(direct interaction)	0.630
SORBS1	ATXN7	psi-mi:“MI:0403”(colocalization)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
INPPL1	SORBS1	psi-mi:“MI:0915”(physical association)	0.580
SORBS1	INPPL1	psi-mi:“MI:0915”(physical association)	0.580
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SORBS1	ABL1	psi-mi:“MI:0915”(physical association)	0.520
ABL1	SORBS1	psi-mi:“MI:0915”(physical association)	0.520
PAK2	SORBS1	psi-mi:“MI:0915”(physical association)	0.520
SORBS1	PAK2	psi-mi:“MI:0915”(physical association)	0.520
SORBS1	Dnm2	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (123): SORBS1 (Affinity Capture-Western), SORBS1 (Co-localization), NCK2 (Affinity Capture-Western), SORBS1 (Proximity Label-MS), SORBS1 (Proximity Label-MS), SORBS1 (Proximity Label-MS), SORBS1 (Affinity Capture-MS), SORBS1 (Affinity Capture-MS), SORBS1 (Affinity Capture-MS), SORBS1 (Affinity Capture-MS), SORBS1 (Affinity Capture-MS), INSM1 (Two-hybrid), SORBS1 (Two-hybrid), SORBS1 (Proximity Label-MS), SORBS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1L8H8C0, A0A1L8HFX9, A0A2R6X6S3, A0JM08, A2ARZ3, A2RUV4, A5WUN7, A6QP06, D4AEC2, E9Q309, O76039, P51960, Q03898, Q05935, Q06190, Q08AD1, Q08D57, Q0WPH8, Q3KQW7, Q3UTQ8, Q498L0, Q5RAU1, Q5SW79, Q5T0W9, Q5T5U3, Q5VT06, Q62770, Q66J90, Q69Z38, Q6A065, Q6DFG0, Q6DFV3, Q6IRN6, Q71M21, Q80TN7, Q8AV28, Q8C1B1, Q8IVL0, Q8IZ21

Diamond homologs: A0JNB0, A1CEK6, A1DFN5, A1Y2K1, A2QW93, A4IF63, A4RF61, A5D7F8, A5D8S5, A6QLK6, A7A261, B0BNA1, B1V8A0, D2GXS7, D3ZQG6, F1RDG9, F7H9X2, O01498, O08641, O35179, O35180, O35964, O43125, O70277, O75382, P06241, P09769, P0CR79, P13406, P19706, P19878, P27446, P32793, P39688, P43603, P62484, Q08012, Q09822, Q0CJU8, Q0U6X7

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	SORBS1	phosphorylation
SORBS1	up-regulates	CBL	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Activation of BAD and translocation to mitochondria	7	100.5×	5e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	88.7×	7e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	88.7×	7e-11
Activation of BH3-only proteins	7	65.6×	5e-10
RHO GTPases activate PKNs	8	47.9×	3e-10
Intrinsic Pathway for Apoptosis	7	38.7×	2e-08
FOXO-mediated transcription	6	38.0×	3e-07
Apoptosis	9	28.5×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	28.2×	4e-04
intracellular protein localization	8	12.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	193
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

6774 predictions. Top by Δscore:

Variant	Effect	Δscore
10:95318315:CTTA:C	donor_loss	1.0000
10:95318316:TTA:T	donor_loss	1.0000
10:95318317:TA:T	donor_loss	1.0000
10:95318318:A:AC	donor_gain	1.0000
10:95318318:A:AT	donor_loss	1.0000
10:95318319:C:CC	donor_gain	1.0000
10:95318319:CCAA:C	donor_gain	1.0000
10:95318428:TAAAT:T	acceptor_gain	1.0000
10:95318433:C:CC	acceptor_gain	1.0000
10:95339128:GATAC:G	donor_loss	1.0000
10:95339129:ATACC:A	donor_loss	1.0000
10:95339130:TAC:T	donor_loss	1.0000
10:95339131:ACCT:A	donor_loss	1.0000
10:95339323:TCACC:T	acceptor_gain	1.0000
10:95339324:CACC:C	acceptor_gain	1.0000
10:95339324:CACCC:C	acceptor_gain	1.0000
10:95339326:CC:C	acceptor_gain	1.0000
10:95339327:CC:C	acceptor_gain	1.0000
10:95346404:A:AC	donor_gain	1.0000
10:95346405:C:CC	donor_gain	1.0000
10:95354877:TTTA:T	donor_loss	1.0000
10:95354878:TTACC:T	donor_loss	1.0000
10:95354881:C:A	donor_loss	1.0000
10:95354881:CCT:C	donor_gain	1.0000
10:95354883:T:TA	donor_gain	1.0000
10:95354966:AT:A	acceptor_gain	1.0000
10:95354968:C:CC	acceptor_gain	1.0000
10:95354969:T:C	acceptor_gain	1.0000
10:95354970:T:C	acceptor_gain	1.0000
10:95357820:T:C	acceptor_gain	1.0000

AlphaMissense

8399 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:95339279:C:A	G907W	1.000
10:95339279:C:G	G907R	1.000
10:95339279:C:T	G907R	1.000
10:95341649:A:T	V820D	1.000
10:95351331:C:G	A754P	1.000
10:95351351:A:G	L747P	1.000
10:95372034:A:G	W585R	1.000
10:95372034:A:T	W585R	1.000
10:95376011:A:G	W567R	1.000
10:95376011:A:T	W567R	1.000
10:95397260:C:A	W394C	1.000
10:95397260:C:G	W394C	1.000
10:95397262:A:G	W394R	1.000
10:95397262:A:T	W394R	1.000
10:95410650:A:G	L313P	1.000
10:95315126:C:T	G1271D	0.999
10:95318320:C:G	G1271R	0.999
10:95318329:A:G	W1268R	0.999
10:95318329:A:T	W1268R	0.999
10:95318352:A:T	V1260D	0.999
10:95318358:A:T	V1258D	0.999
10:95337198:A:G	W988R	0.999
10:95337198:A:T	W988R	0.999
10:95339245:A:G	F918S	0.999
10:95339252:C:G	G916R	0.999
10:95339278:C:T	G907E	0.999
10:95339288:A:G	W904R	0.999
10:95339288:A:T	W904R	0.999
10:95339305:C:G	R898P	0.999
10:95341292:A:G	F888S	0.999

dbSNP variants (sampled 300 via entrez): RS1000004287 (10:95455859 C>T), RS1000008956 (10:95358962 A>G), RS1000018071 (10:95324852 C>A,G,T), RS1000030865 (10:95453836 G>A), RS1000044668 (10:95446011 C>T), RS1000056781 (10:95456159 A>T), RS1000063016 (10:95506536 C>G,T), RS1000063378 (10:95316356 C>G,T), RS1000067395 (10:95411793 G>A,T), RS1000102848 (10:95440209 G>A), RS1000127088 (10:95463867 G>A), RS1000150167 (10:95404308 A>G), RS1000167095 (10:95472597 C>A,T), RS1000170372 (10:95405826 C>T), RS1000179766 (10:95395848 T>C,G)

Disease associations

OMIM: gene MIM:605264 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000854_3	Suicide risk	3.000000e-06
GCST001762_69	Obesity-related traits	4.000000e-06
GCST002716_1	Diabetic nephropathy in type 1 diabetes	6.000000e-07
GCST003182_4	Staphylococcus aureus nasal carriage (persistent)	2.000000e-06
GCST007045_33	PR interval	4.000000e-16
GCST008058_216	Estimated glomerular filtration rate	2.000000e-12
GCST010321_126	PR interval	9.000000e-31
GCST90002383_493	Hematocrit	1.000000e-10
GCST90002395_32	Mean platelet volume	7.000000e-12
GCST90002403_224	Red blood cell count	5.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004321	attempted suicide
EFO:0007757	persistent Staphylococcus aureus carrier status
EFO:0004462	PR interval
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067350 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	6
Valproic Acid	affects cotreatment, increases expression	5
bisphenol A	decreases expression, increases expression, affects cotreatment, decreases methylation	4
(+)-JQ1 compound	increases expression	3
Arsenic	affects methylation, increases methylation	2
Dexamethasone	increases expression, affects cotreatment	2
Smoke	decreases reaction, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
methylselenic acid	increases expression	1
decabromobiphenyl ether	decreases expression	1
quercitrin	affects expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	affects methylation	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652509	Binding	Binding affinity to human SORBS1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer