SPTBN1

Summary

SPTBN1 (spectrin beta, non-erythrocytic 1, HGNC:11275) is a protein-coding gene on chromosome 2p16.2, encoding Spectrin beta chain, non-erythrocytic 1 (Q01082). Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.

Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats which are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6711 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental delay, impaired speech, and behavioral abnormalities (Definitive, ClinGen)
• GWAS associations: 53
• Clinical variants (ClinVar): 701 total — 24 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 188
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11275
Approved symbol	SPTBN1
Name	spectrin beta, non-erythrocytic 1
Location	2p16.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115306
Ensembl biotype	protein_coding
OMIM	182790
Entrez	6711

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 retained_intron

ENST00000333896, ENST00000356805, ENST00000389980, ENST00000467371, ENST00000496323, ENST00000602898, ENST00000898759, ENST00000898760, ENST00000898761, ENST00000898762, ENST00000937940, ENST00000937941

RefSeq mRNA: 2 — MANE Select: NM_003128 NM_003128, NM_178313

CCDS: CCDS33198, CCDS33199

Canonical transcript exons

ENST00000356805 — 36 exons

Exon	Start	End
ENSE00001036008	54646194	54646475
ENSE00001036013	54637713	54637803
ENSE00001036016	54645229	54645453
ENSE00001036019	54622300	54622487
ENSE00001036020	54649615	54649989
ENSE00001036026	54623479	54623596
ENSE00001036038	54624804	54624962
ENSE00001036039	54647131	54647261
ENSE00001036040	54645928	54646017
ENSE00001070390	54632566	54632768
ENSE00001070394	54617608	54617688
ENSE00001070397	54628097	54628250
ENSE00001070398	54630855	54631611
ENSE00001070399	54653609	54653853
ENSE00001070402	54625932	54626234
ENSE00001070403	54629892	54630029
ENSE00001070404	54628933	54629803
ENSE00001070405	54618078	54618193
ENSE00001289535	54659936	54659999
ENSE00001306451	54664453	54664691
ENSE00001324724	54526372	54526566
ENSE00001332209	54668351	54671446
ENSE00001404051	54456327	54456518
ENSE00001507425	54648986	54649190
ENSE00001507426	54644323	54644586
ENSE00001622258	54599092	54599243
ENSE00002467613	54616207	54616298
ENSE00002476602	54612161	54612334
ENSE00002484952	54621400	54621512
ENSE00002503878	54642983	54643129
ENSE00003506591	54655070	54655208
ENSE00003566929	54665915	54666088
ENSE00003605227	54667604	54667646
ENSE00003634635	54659154	54659266
ENSE00003637920	54657850	54658046
ENSE00003649234	54655914	54655998

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 133.6247 / max 2840.0230, expressed in 1785 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20256	91.0570	1498
20283	22.2687	1563
20262	6.1313	1206
20258	2.6528	833
20281	2.3721	825
20284	2.3206	1012
20260	1.9136	934
20285	1.0921	626
20316	0.7317	403
20287	0.5150	287

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.76	gold quality
trigeminal ganglion	UBERON:0001675	99.73	gold quality
skin of hip	UBERON:0001554	99.66	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.64	gold quality
substantia nigra pars compacta	UBERON:0001965	99.62	gold quality
lateral globus pallidus	UBERON:0002476	99.58	gold quality
synovial joint	UBERON:0002217	99.56	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.56	gold quality
superior vestibular nucleus	UBERON:0007227	99.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.55	gold quality
medulla oblongata	UBERON:0001896	99.51	gold quality
vena cava	UBERON:0004087	99.49	gold quality
adult organism	UBERON:0007023	99.46	gold quality
renal medulla	UBERON:0000362	99.45	gold quality
globus pallidus	UBERON:0001875	99.45	gold quality
parietal lobe	UBERON:0001872	99.44	gold quality
middle temporal gyrus	UBERON:0002771	99.44	gold quality
pons	UBERON:0000988	99.43	gold quality
urethra	UBERON:0000057	99.42	gold quality
medial globus pallidus	UBERON:0002477	99.42	gold quality
postcentral gyrus	UBERON:0002581	99.42	gold quality
choroid plexus epithelium	UBERON:0003911	99.42	gold quality
pericardium	UBERON:0002407	99.41	gold quality
dorsal root ganglion	UBERON:0000044	99.39	gold quality
calcaneal tendon	UBERON:0003701	99.39	gold quality
subthalamic nucleus	UBERON:0001906	99.36	gold quality
upper leg skin	UBERON:0004262	99.36	gold quality
right lung	UBERON:0002167	99.34	gold quality
ventral tegmental area	UBERON:0002691	99.34	gold quality
lower lobe of lung	UBERON:0008949	99.34	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	701.88
E-MTAB-10287	yes	66.47
E-MTAB-8142	yes	42.22
E-CURD-112	yes	38.22
E-HCAD-10	yes	37.95
E-CURD-119	yes	36.61
E-CURD-46	yes	32.83
E-MTAB-6701	yes	29.50
E-MTAB-8410	yes	28.75
E-GEOD-135922	yes	27.62
E-GEOD-81547	yes	23.45
E-HCAD-1	yes	18.28
E-MTAB-8271	yes	14.88
E-MTAB-6678	yes	13.38
E-HCAD-9	yes	12.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, FOS

miRNA regulators (miRDB)

121 targeting SPTBN1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692A	100.00	74.40	6850
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-1184	99.99	68.19	1458
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 37)

• High affinity and slow overall kinetics of association/dissociation of beta II-spectrin may suit it well to a role in strengthening cell junctions and providing stable anchorage for transmembrane proteins at points specified by cell-adhesion molecules. (PMID:12820899)
• Quantitative analysis of erythrocyte membrane proteins revealed increase in beta-spectrin from patients with homozygous and heterozygous forms of beta-thalassemia. (PMID:15310273)
• ankyrin-G and beta(2)-spectrin are functional partners in biogenesis of the lateral membrane of epithelial cells (PMID:17074766)
• because both the T2159E mutant and the wild-type allow neuritogenesis, we conclude that the short C-terminal betaII-spectrin is phosphorylated during this process (PMID:17088250)
• TGF-beta signaling and Smad adaptor embryonic liver fodrin (ELF) suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. (PMID:17546056)
• E-cadherin thus requires both ankyrin-G and beta-2-spectrin for its cellular localization in early embryos as well as cultured epithelial cells. (PMID:17620337)
• Our results therefore indicate the importance of N-terminal region for lipid-binding activity of the beta-spectrin ankyrin-binding domain and its substantial role in maintaining the spectrin-based skeleton distribution. (PMID:17716929)
• analysis of the conformational change of erythroid alpha-spectrin at the tetramerization site upon binding beta-spectrin (PMID:17905835)
• Characterization of the 2p21 breakpoint identified the SPTBN1 gene in myeloproliferative disorders. (PMID:18262053)
• ELF, a TGF-beta adaptor and signaling molecule, functions as a critical adaptor protein in TGF-beta modulation of angiogenesis as well as cell cycle progression. (PMID:18704924)
• Results suggest that epigenetic silencing of SPTBN1 (beta2SP) is a new potential causal factor in BWS patients. (PMID:20739274)
• reduced SPTBN1 expression correlated with shorter survival of pancreatic cancer patients, suggesting a tumor suppressor function of this gene (PMID:20886430)
• Results suggest that it is possible for cellular proteins to differentially associate with the C-termini of different beta-spectrin isoforms to regulate alpha- and beta-spectrin association to form functional spectrin tetramers. (PMID:21412925)
• These results suggest that alpha-synuclein modulates neurite outgrowth by interacting with cytoskeletal proteins such as SPTBN1. (PMID:22771809)
• genetic association study in population of 1,012 Han women in China: Data suggest that an SNP in SPTBN1 (rs11898505) is associated with osteoporotic fractures and bone mineral density of lumbar spine in aging women. (PMID:22798246)
• in human HCC tissues, SPTBN1 expression correlated negatively with expression levels of STAT3, ATF3, and CREB2; SMAD3 expression correlated negatively with STAT3 expression (PMID:25096061)
• decreased SPTBN1 and kallistatin gene expression associated with decreased relapse-free survival in hepatocellular carcinoma (PMID:25307947)
• betaII spectrin is critical for normal myocyte electric activity. Dysfunction in the betaII spectrin-dependent cytoskeleton in cardiomyocytes contributes to human arrhythmia. (PMID:25632041)
• TGF-beta1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. (PMID:25880619)
• Subjects whose head and neck tumors expressed spectrin were 4.60 times more likely (hazard ratio; 95% confidence interval: 1.88-11.25) to die at any given time when compared with those without spectrin (P = .001). (PMID:27095047)
• c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis. (PMID:27496196)
• beta2 spectrin induced the differentiation of liver cancer stem cells, and then repressed the CSCs properties in liver tumorinitiating cells. Transduction of beta2SP into liver CSCs resulted in a reduction in colony formation ability, spheroid formation capacity, invasive activity, chemo-resistance properties, tumorigenicity in vivo. (PMID:29555987)
• Data suggeset the novel mutation (c.5650G > C/p.Ala1884Pro) of beta-spectrin (SPTB) to be the genetic lesion in this family of hereditary spherocytosis (HS). (PMID:30690801)
• SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway. (PMID:32516133)
• betaII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases. (PMID:33390831)
• SPTBN1 inhibits inflammatory responses and hepatocarcinogenesis via the stabilization of SOCS1 and downregulation of p65 in hepatocellular carcinoma. (PMID:33754058)
• Heterozygous variants in SPTBN1 cause intellectual disability and autism. (PMID:33847457)
• Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome. (PMID:34211179)
• SPTBN1 inhibits growth and epithelial-mesenchymal transition in breast cancer by downregulating miR-21. (PMID:34358482)
• SPTBN1 attenuates rheumatoid arthritis synovial cell proliferation, invasion, migration and inflammatory response by binding to PIK3R2. (PMID:36444616)
• SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner. (PMID:36527113)
• Clinical significance of nonerythrocytic spectrin Beta 1 (SPTBN1) in human kidney renal clear cell carcinoma and uveal melanoma: a study based on Pan-Cancer Analysis. (PMID:37013511)
• Tumor cell SPTBN1 inhibits M2 polarization of macrophages by suppressing CXCL1 expression. (PMID:37921259)
• SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma. (PMID:38069214)
• Postsynaptic beta1 spectrin maintains Na[+] channels at the neuromuscular junction. (PMID:38441922)
• Identification of bone mineral density associated genes with shared genetic architectures across multiple tissues: Functional insights for EPDR1, PKDCC, and SPTBN1. (PMID:38683846)
• Cardiomyocyte betaII spectrin plays a critical role in maintaining cardiac function by regulating mitochondrial respiratory function. (PMID:38832923)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sptbn1	ENSDARG00000102883
danio_rerio	sptbn1	ENSDARG00000105428
mus_musculus	Sptbn1	ENSMUSG00000020315
rattus_norvegicus	Sptbn1	ENSRNOG00000005434
drosophila_melanogaster	beta-Spec	FBGN0250788

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Spectrin beta chain, non-erythrocytic 1 — Q01082 (reviewed: Q01082)

Alternative names: Beta-II spectrin, Fodrin beta chain, Spectrin, non-erythroid beta chain 1

All UniProt accessions (3): Q01082, B2ZZ89, F8W6C1

UniProt curated annotations — full annotation on UniProt →

Function. Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function.

Subunit / interactions. Interacts with CAMSAP1. Interacts with ANK2. Interacts with CPNE4 (via VWFA domain). Like erythrocyte spectrin, the spectrin-like proteins are capable to form dimers which can further associate to tetramers. Can form heterodimers with SPTAN1. Isoform Short cannot bind to the axonal protein fodaxin.

Subcellular location. Cytoplasm. Cytoskeleton. Myofibril. Sarcomere. M line. Cytosol. Cell membrane Cell membrane.

Tissue specificity. Isoform 2 is present in brain, lung and kidney (at protein level).

Disease relevance. Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) [MIM:619475] An autosomal dominant disorder characterized by developmental delay with speech impairment, mild to severe intellectual disability, and behavioral abnormalities including autistic features. Additional variable manifestations may include dysmorphic facial features, seizures, hypotonia, motor abnormalities, and hearing loss. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the spectrin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q01082-1	Long	yes
Q01082-2	Short
Q01082-3	2

RefSeq proteins (2): NP_003119, NP_842565 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001605	PH_dom-spectrin-type	Domain
IPR001715	CH_dom	Domain
IPR001849	PH_domain	Domain
IPR002017	Spectrin_repeat	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016343	Spectrin_bsu	Family
IPR018159	Spectrin/alpha-actinin	Repeat
IPR036872	CH_dom_sf	Homologous_superfamily
IPR041681	PH_9	Domain

Pfam: PF00307, PF00435, PF15410

UniProt features (126 total): modified residue 41, sequence variant 26, repeat 17, helix 17, region of interest 5, compositionally biased region 5, splice variant 5, domain 3, strand 2, initiator methionine 1, chain 1, sequence conflict 1, turn 1, glycosylation site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1BKR	X-RAY DIFFRACTION	1.1
3EDV	X-RAY DIFFRACTION	1.95
1AA2	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01082-F1	76.52	0.10

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 (41): 14, 2, 36, 90, 228, 817, 825, 903, 1057, 1076, 1079, 1237, 1388, 1447, 1557, 1805, 1815, 1913, 1989, 2102 …

Glycosylation sites (1): 2324

Function

Pathways and Gene Ontology

Reactome pathways

33 pathways

ID	Pathway
R-HSA-373753	Nephrin family interactions
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea
R-HSA-9703465	Signaling by FLT3 fusion proteins
R-HSA-1266738	Developmental Biology
R-HSA-1500931	Cell-Cell communication
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-373760	L1CAM interactions
R-HSA-392499	Metabolism of proteins
R-HSA-422475	Axon guidance
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling
R-HSA-597592	Post-translational protein modification
R-HSA-9012999	RHO GTPase cycle
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9659379	Sensory processing of sound
R-HSA-9675108	Nervous system development

MSigDB gene sets: 855 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_MEMBRANE_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, HSIAO_HOUSEKEEPING_GENES, MITSIADES_RESPONSE_TO_APLIDIN_DN, AP4_Q6

GO Biological Process (15): mitotic cytokinesis (GO:0000281), plasma membrane organization (GO:0007009), central nervous system development (GO:0007417), central nervous system formation (GO:0021556), actin cytoskeleton organization (GO:0030036), positive regulation of interleukin-2 production (GO:0032743), Golgi to plasma membrane protein transport (GO:0043001), actin filament capping (GO:0051693), regulation of SMAD protein signal transduction (GO:0060390), membrane assembly (GO:0071709), protein localization to plasma membrane (GO:0072659), regulation of protein localization to plasma membrane (GO:1903076), positive regulation of protein localization to plasma membrane (GO:1903078), cytoskeleton organization (GO:0007010), vesicle-mediated transport (GO:0016192)

GO Molecular Function (11): RNA binding (GO:0003723), actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), calmodulin binding (GO:0005516), phospholipid binding (GO:0005543), ankyrin binding (GO:0030506), cadherin binding (GO:0045296), actin filament binding (GO:0051015), GTPase binding (GO:0051020), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (21): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), spectrin (GO:0008091), postsynaptic density (GO:0014069), spectrin-associated cytoskeleton (GO:0014731), cell junction (GO:0030054), axolemma (GO:0030673), cortical actin cytoskeleton (GO:0030864), M band (GO:0031430), cuticular plate (GO:0032437), cell projection (GO:0042995), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), nucleus (GO:0005634), cytoskeleton (GO:0005856), membrane (GO:0016020), cortical cytoskeleton (GO:0030863), protein-containing complex (GO:0032991), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Axon guidance	2
RHO GTPase cycle	2
Sensory processing of sound	2
Cell-Cell communication	1
L1CAM interactions	1
MAPK1/MAPK3 signaling	1
ER to Golgi Anterograde Transport	1
FLT3 signaling in disease	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Nervous system development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein localization to plasma membrane	3
cytoskeleton	3
membrane organization	2
cytoskeleton organization	2
cytoskeletal protein binding	2
binding	2
intracellular membraneless organelle	2
cortical actin cytoskeleton	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
endomembrane system organization	1
nervous system development	1
system development	1
central nervous system morphogenesis	1
anatomical structure formation involved in morphogenesis	1
actin filament-based process	1
positive regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
SMAD protein signal transduction	1
regulation of intracellular signal transduction	1
cellular component assembly	1
membrane biogenesis	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of protein localization to cell periphery	1
regulation of protein localization to 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
organelle organization	1
transport	1
cellular process	1

Protein interactions and networks

STRING

1644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPTBN1	ANK2	Q01484	991
SPTBN1	SPTAN1	Q13813	986
SPTBN1	ANK3	Q12955	868
SPTBN1	ANK1	P16157	860
SPTBN1	EPB41	P11171	823
SPTBN1	SPTA1	P02549	820
SPTBN1	SMAD3	P84022	802
SPTBN1	CNTNAP1	P78357	693
SPTBN1	NF2	P35240	690
SPTBN1	NRCAM	Q92823	606
SPTBN1	EIF3C	Q99613	596
SPTBN1	ELF3	P78545	587
SPTBN1	NFASC	O94856	582
SPTBN1	SLC1A6	P48664	578
SPTBN1	HGS	O14964	573

IntAct

241 interactions, top by confidence:

A	B	Type	Score
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SPTBN1	NF2	psi-mi:“MI:0915”(physical association)	0.650
NF2	SPTBN1	psi-mi:“MI:0915”(physical association)	0.650
SPTBN1	NF2	psi-mi:“MI:0407”(direct interaction)	0.650
SPTAN1	SPTBN1	psi-mi:“MI:0407”(direct interaction)	0.610
SPTBN1	SPTAN1	psi-mi:“MI:0407”(direct interaction)	0.610
SPTBN1	SPTAN1	psi-mi:“MI:0915”(physical association)	0.610
SPTA1	SPTBN1	psi-mi:“MI:0407”(direct interaction)	0.560
SPTBN1	SPTA1	psi-mi:“MI:0407”(direct interaction)	0.560
SPTBN1	NF2	psi-mi:“MI:0915”(physical association)	0.550
NF2	SPTBN1	psi-mi:“MI:0915”(physical association)	0.550
	SPTBN1	psi-mi:“MI:0407”(direct interaction)	0.440
SPTBN1		psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (547): SPTBN1 (Affinity Capture-MS), SPTBN1 (Two-hybrid), SPTBN1 (Affinity Capture-RNA), NCAPD3 (Co-fractionation), SPTBN1 (Co-fractionation), SPTBN1 (Co-fractionation), SPTBN1 (Co-fractionation), SPTBN1 (Affinity Capture-MS), SPTBN1 (Reconstituted Complex), SPTBN1 (Proximity Label-MS), SPTBN1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS)

ESM2 similar proteins: A5D7D1, L7UZ85, O43707, O88990, P05094, P11277, P12814, P15508, P18091, P20111, P26232, P30997, P35609, P46940, P57780, Q00078, Q00963, Q01082, Q08043, Q0E908, Q0III9, Q13576, Q2PFV7, Q3B7N2, Q3UQ44, Q3ZC55, Q4QR29, Q4WVG0, Q5M7J9, Q5R416, Q5RCS6, Q61301, Q62018, Q62261, Q6DEU9, Q6INS3, Q6NXC0, Q6PD62, Q7G188, Q7PKQ5

Diamond homologs: A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094, P05095, P07751, P11277, P11530, P11531, P11532, P11533, P12814, P13395, P13466, P15508, P16086, P16546, P18091, P20111, P21333, P30427, P35609

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PJA1	down-regulates	SPTBN1	ubiquitination
CSNK2A1	down-regulates	SPTBN1	phosphorylation
ANK3	“up-regulates activity”	SPTBN1	binding
TGFBR1	up-regulates	SPTBN1	phosphorylation
PRKACA	“down-regulates activity”	SPTBN1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
Apoptotic cleavage of cellular proteins	6	20.4×	6e-05
Apoptotic execution phase	6	20.4×	6e-05
RHO GTPases activate PAKs	5	19.4×	3e-04
Interaction between L1 and Ankyrins	6	15.8×	1e-04
Sensory processing of sound	7	15.4×	6e-05
Signaling by RAS mutants	5	15.1×	7e-04
RHO GTPases activate IQGAPs	5	12.4×	2e-03
Signaling by high-kinase activity BRAF mutants	5	11.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
neuron projection morphogenesis	6	9.8×	7e-03
MAPK cascade	9	8.1×	1e-03
actin cytoskeleton organization	17	7.9×	9e-08
actin filament organization	11	7.7×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	33
Uncertain significance	495
Likely benign	79
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1172531	NM_003128.3(SPTBN1):c.803C>G (p.Thr268Ser)	Pathogenic
1195995	NM_003128.3(SPTBN1):c.549C>A (p.Cys183Ter)	Pathogenic
1195996	NM_003128.3(SPTBN1):c.614G>A (p.Gly205Asp)	Pathogenic
1195997	NM_003128.3(SPTBN1):c.749T>G (p.Leu250Arg)	Pathogenic
1195998	NM_003128.3(SPTBN1):c.2674G>T (p.Glu892Ter)	Pathogenic
1195999	NM_003128.3(SPTBN1):c.5656G>C (p.Glu1886Gln)	Pathogenic
1318958	NM_003128.3(SPTBN1):c.543GTG[1] (p.Trp182del)	Pathogenic
1326847	NM_003128.3(SPTBN1):c.2275_2285del (p.Trp759fs)	Pathogenic
1699089	NM_003128.3(SPTBN1):c.4718dup (p.Trp1574fs)	Pathogenic
1804061	NM_003128.3(SPTBN1):c.5961+2T>C	Pathogenic
2231751	NM_003128.3(SPTBN1):c.3523del (p.Leu1175fs)	Pathogenic
2406676	NM_003128.3(SPTBN1):c.4341_4344del (p.Ser1447fs)	Pathogenic
2438401	NM_003128.3(SPTBN1):c.176C>G (p.Thr59Ser)	Pathogenic
2444107	NM_003128.3(SPTBN1):c.865C>T (p.Arg289Ter)	Pathogenic
2581431	NM_003128.3(SPTBN1):c.5304_5305del (p.Gly1769fs)	Pathogenic
3322435	NM_003128.3(SPTBN1):c.968_969insA (p.Ile324fs)	Pathogenic
3343363	NM_003128.3(SPTBN1):c.1853del (p.Phe618fs)	Pathogenic
3375416	NM_003128.3(SPTBN1):c.1828C>T (p.Arg610Ter)	Pathogenic
3602945	NM_003128.3(SPTBN1):c.2917del (p.Glu973fs)	Pathogenic
3899568	NM_003128.3(SPTBN1):c.5233C>T (p.Arg1745Ter)	Pathogenic
4726309	NM_003128.3(SPTBN1):c.2138del (p.Glu713fs)	Pathogenic
4733773	NM_003128.3(SPTBN1):c.6376C>T (p.Gln2126Ter)	Pathogenic
4819107	NM_003128.3(SPTBN1):c.3854_3855del (p.Gln1285fs)	Pathogenic
4845605	NM_003128.3(SPTBN1):c.4997+1G>A	Pathogenic
1315858	NM_003128.3(SPTBN1):c.1471G>C (p.Glu491Gln)	Likely pathogenic
1318838	NM_003128.3(SPTBN1):c.6731C>A (p.Ala2244Asp)	Likely pathogenic
1321938	NM_003128.3(SPTBN1):c.811G>A (p.Val271Met)	Likely pathogenic
1683604	NM_003128.3(SPTBN1):c.3510_3529dup (p.Asp1177fs)	Likely pathogenic
1685453	NM_003128.3(SPTBN1):c.586C>T (p.His196Tyr)	Likely pathogenic
1685454	NM_003128.3(SPTBN1):c.1043G>C (p.Arg348Pro)	Likely pathogenic

SpliceAI

6069 predictions. Top by Δscore:

Variant	Effect	Δscore
2:54468933:GTTT:G	donor_gain	1.0000
2:54468934:TTTT:T	donor_gain	1.0000
2:54526366:TCATA:T	acceptor_gain	1.0000
2:54526367:CATA:C	acceptor_gain	1.0000
2:54526368:A:AG	acceptor_gain	1.0000
2:54526368:ATAGA:A	acceptor_gain	1.0000
2:54526369:T:G	acceptor_gain	1.0000
2:54526369:TAG:T	acceptor_loss	1.0000
2:54526369:TAGA:T	acceptor_gain	1.0000
2:54526370:A:AG	acceptor_gain	1.0000
2:54526370:A:T	acceptor_gain	1.0000
2:54526370:AG:A	acceptor_loss	1.0000
2:54526371:G:GC	acceptor_gain	1.0000
2:54526371:GA:G	acceptor_gain	1.0000
2:54526371:GAA:G	acceptor_gain	1.0000
2:54526371:GAAC:G	acceptor_gain	1.0000
2:54526371:GAACT:G	acceptor_gain	1.0000
2:54526562:GGCAG:G	donor_gain	1.0000
2:54526563:GCAG:G	donor_gain	1.0000
2:54526563:GCAGG:G	donor_gain	1.0000
2:54526564:CAGG:C	donor_loss	1.0000
2:54526565:AGG:A	donor_loss	1.0000
2:54526566:GGT:G	donor_loss	1.0000
2:54526568:T:A	donor_loss	1.0000
2:54599083:T:A	acceptor_gain	1.0000
2:54599087:T:TA	acceptor_gain	1.0000
2:54599087:TGCA:T	acceptor_loss	1.0000
2:54599089:CAG:C	acceptor_loss	1.0000
2:54599090:A:AG	acceptor_gain	1.0000
2:54599090:AGA:A	acceptor_loss	1.0000

AlphaMissense

15835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:54526536:T:C	F40L	1.000
2:54526537:T:G	F40C	1.000
2:54526538:T:A	F40L	1.000
2:54526538:T:G	F40L	1.000
2:54526539:G:A	E41K	1.000
2:54526548:C:A	R44S	1.000
2:54526552:T:C	I45T	1.000
2:54526561:T:C	L48P	1.000
2:54599111:G:C	Q56H	1.000
2:54599111:G:T	Q56H	1.000
2:54599121:T:C	F60L	1.000
2:54599122:T:C	F60S	1.000
2:54599123:C:A	F60L	1.000
2:54599123:C:G	F60L	1.000
2:54599130:T:A	W63R	1.000
2:54599130:T:C	W63R	1.000
2:54599132:G:C	W63C	1.000
2:54599132:G:T	W63C	1.000
2:54599146:T:C	L68P	1.000
2:54599196:G:A	G85R	1.000
2:54599196:G:C	G85R	1.000
2:54599197:G:A	G85E	1.000
2:54599197:G:T	G85V	1.000
2:54599215:T:C	L91P	1.000
2:54599218:T:C	L92P	1.000
2:54612176:G:A	G106R	1.000
2:54612176:G:C	G106R	1.000
2:54612177:G:A	G106E	1.000
2:54612183:T:A	M108K	1.000
2:54612183:T:C	M108T	1.000

dbSNP variants (sampled 300 via entrez): RS1000014669 (2:54469317 G>T), RS1000020342 (2:54499340 C>G,T), RS1000022489 (2:54635739 T>C), RS1000027526 (2:54567141 A>G), RS1000027760 (2:54617164 C>T), RS1000041732 (2:54654259 A>G), RS1000049669 (2:54544614 C>A), RS1000090744 (2:54610439 T>A), RS1000094268 (2:54474821 C>A,G), RS1000095994 (2:54659600 A>G,T), RS1000138604 (2:54491641 G>A), RS1000139689 (2:54615741 C>T), RS1000182391 (2:54620743 T>G), RS1000185003 (2:54489377 A>G), RS1000185508 (2:54563987 A>G)

Disease associations

OMIM: gene MIM:182790 | disease phenotypes: MIM:619475, MIM:616917, MIM:619964

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental delay, impaired speech, and behavioral abnormalities	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
developmental delay, impaired speech, and behavioral abnormalities	Definitive	AD

Mondo (6): developmental delay, impaired speech, and behavioral abnormalities (MONDO:0859178), neurodevelopmental disorder (MONDO:0700092), pervasive developmental disorder (MONDO:0000594), intellectual disability, autosomal recessive 53 (MONDO:0014832), developmental delay, impaired speech, and behavioral abnormalities, with or without seizures (MONDO:0859263), intellectual disability (MONDO:0001071)

Orphanet (3): Rare pervasive developmental disorder (Orphanet:168778), Early-onset epilepsy-intellectual disability-brain anomalies syndrome (Orphanet:488635), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

188 total (30 of 188 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000054	Micropenis
HP:0000152	Abnormality of head or neck
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000280	Coarse facial features
HP:0000289	Broad philtrum
HP:0000293	Full cheeks
HP:0000300	Oval face
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000378	Cupped ear
HP:0000388	Otitis media
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000437	Depressed nasal tip

GWAS associations

53 associations (top):

Study	Trait	p-value
GCST000180_3	Bone mineral density (spine)	8.000000e-07
GCST000295_4	Bone mineral density (spine)	4.000000e-06
GCST000494_15	Bone mineral density (spine)	2.000000e-08
GCST001482_13	Lumbar spine bone mineral density	2.000000e-18
GCST001561_1	Myopia (pathological)	3.000000e-07
GCST002333_1	Bone properties (heel)	6.000000e-06
GCST002335_2	Bone properties (heel)	4.000000e-13
GCST004350_1	Bone ultrasound measurement (velocity of sound)	2.000000e-08
GCST004351_25	Bone ultrasound measurement (broadband ultrasound attenuation)	2.000000e-13
GCST004351_3	Bone ultrasound measurement (broadband ultrasound attenuation)	2.000000e-09
GCST005580_162	Intraocular pressure	1.000000e-09
GCST005580_283	Intraocular pressure	1.000000e-09
GCST005796_3	Lumbar spine bone mineral density	3.000000e-09
GCST006288_230	Heel bone mineral density	1.000000e-63
GCST006288_231	Heel bone mineral density	8.000000e-20
GCST006288_266	Heel bone mineral density	2.000000e-45
GCST006288_267	Heel bone mineral density	8.000000e-26
GCST006288_573	Heel bone mineral density	2.000000e-110
GCST006288_574	Heel bone mineral density	2.000000e-44
GCST006394_44	Intraocular pressure	8.000000e-09
GCST006412_21	Intraocular pressure	3.000000e-09
GCST006423_1	Fracture	3.000000e-14
GCST006979_1	Heel bone mineral density	1.000000e-280
GCST006979_2	Heel bone mineral density	4.000000e-11
GCST006979_3	Heel bone mineral density	1.000000e-13
GCST006979_4	Heel bone mineral density	2.000000e-69
GCST007014_7	Lumbar spine bone mineral density (trabecular)	1.000000e-07
GCST007015_16	Lumbar spine bone mineral density (integral)	2.000000e-06
GCST007998_10	Intraocular pressure	2.000000e-11
GCST008058_84	Estimated glomerular filtration rate	9.000000e-22

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0005654	velocity of sound measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0004695	intraocular pressure measurement
EFO:0007701	spine bone mineral density
EFO:0009270	heel bone mineral density
EFO:0007620	volumetric bone mineral density
EFO:0004531	urate measurement
EFO:0004462	PR interval
EFO:0004469	HOMA-B
EFO:0004327	electrocardiography
EFO:0007992	basophil percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002659	Child Development Disorders, Pervasive	F03.625.164
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725089 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.04	Kd	90.81	nM	CHEMBL5653589
7.04	ED50	90.81	nM	CHEMBL5653589
5.79	Kd	1609	nM	CHEMBL3752910
5.79	ED50	1609	nM	CHEMBL3752910
5.38	IC50	4140	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149475: Binding affinity to human SPTBN1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0908	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149475: Binding affinity to human SPTBN1 incubated for 45 mins by Kinobead based pull down assay	kd	1.6088	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178833: Inhibition of SPTBN1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	4.1400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
bisphenol A	affects expression, increases expression	3
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, decreases expression, decreases phosphorylation	2
Nickel	decreases expression	2
Quercetin	increases expression, increases phosphorylation	2
Silicon Dioxide	decreases methylation, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
lead acetate	affects cotreatment, decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
afimoxifene	decreases expression	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
sulindac sulfide	decreases expression	1
ochratoxin A	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652517	Binding	Binding affinity to human SPTBN1 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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
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NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
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NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
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NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice