STMN1

Summary

STMN1 (stathmin 1, HGNC:6510) is a protein-coding gene on chromosome 1p36.11, encoding Stathmin (P16949). Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. In precision oncology, STMN1 EXPRESSION is associated with resistance to Paclitaxel in Endometrial Carcinoma (CIViC Level B).

This gene belongs to the stathmin family of genes. It encodes a ubiquitous cytosolic phosphoprotein proposed to function as an intracellular relay integrating regulatory signals of the cellular environment. The encoded protein is involved in the regulation of the microtubule filament system by destabilizing microtubules. It prevents assembly and promotes disassembly of microtubules. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3925 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 11 total
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_005563

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6510
Approved symbol	STMN1
Name	stathmin 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	SMN, OP18, PR22, PP19, PP17, Lag, FLJ32206
Ensembl gene	ENSG00000117632
Ensembl biotype	protein_coding
OMIM	151442
Entrez	3925

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 30 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000357865, ENST00000374291, ENST00000399728, ENST00000426559, ENST00000446334, ENST00000455785, ENST00000465604, ENST00000485226, ENST00000513116, ENST00000871159, ENST00000871160, ENST00000871161, ENST00000871162, ENST00000871163, ENST00000871164, ENST00000871165, ENST00000871166, ENST00000871167, ENST00000935128, ENST00000935129, ENST00000935130, ENST00000935131, ENST00000935132, ENST00000935133, ENST00000935134, ENST00000935135, ENST00000935136, ENST00000935137, ENST00000935138, ENST00000935139, ENST00000935140, ENST00000962618, ENST00000962619

RefSeq mRNA: 4 — MANE Select: NM_005563 NM_001145454, NM_005563, NM_203399, NM_203401

CCDS: CCDS269, CCDS44090

Canonical transcript exons

ENST00000455785 — 5 exons

Exon	Start	End
ENSE00000759932	25901491	25901682
ENSE00001927205	25900116	25901087
ENSE00003532778	25903641	25903813
ENSE00003588498	25904664	25904738
ENSE00003841980	25906389	25906419

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 159.6099 / max 5074.5932, expressed in 1797 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11119	149.7744	1786
11121	3.0434	1272
11113	1.9378	769
11112	1.7423	450
11117	1.0263	295
11116	0.7725	430
11115	0.5927	253
11118	0.3698	168
11105	0.2249	115
11122	0.0874	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.98	gold quality
ganglionic eminence	UBERON:0004023	99.93	gold quality
ventricular zone	UBERON:0003053	99.84	gold quality
right frontal lobe	UBERON:0002810	99.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.75	gold quality
right testis	UBERON:0004534	99.68	gold quality
left testis	UBERON:0004533	99.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.42	gold quality
cerebellar hemisphere	UBERON:0002245	99.32	gold quality
cerebellar cortex	UBERON:0002129	99.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.14	gold quality
prefrontal cortex	UBERON:0000451	98.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.94	gold quality
tibial nerve	UBERON:0001323	98.81	gold quality
testis	UBERON:0000473	98.57	gold quality
cingulate cortex	UBERON:0003027	98.54	gold quality
anterior cingulate cortex	UBERON:0009835	98.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.04	gold quality
stromal cell of endometrium	CL:0002255	98.02	gold quality
rectum	UBERON:0001052	97.95	gold quality
left ovary	UBERON:0002119	97.78	gold quality
spinal cord	UBERON:0002240	97.70	gold quality
right ovary	UBERON:0002118	97.64	gold quality
adrenal tissue	UBERON:0018303	97.64	gold quality
amygdala	UBERON:0001876	97.63	gold quality
colonic epithelium	UBERON:0000397	97.60	gold quality
sural nerve	UBERON:0015488	97.54	gold quality
mucosa of transverse colon	UBERON:0004991	97.47	gold quality
neocortex	UBERON:0001950	97.24	gold quality
cerebellum	UBERON:0002037	97.18	gold quality

Single-cell (SCXA)

Detected in 86 experiment(s), a significant marker in 67.

Experiment	Marker?	Max mean expression
E-MTAB-6379	yes	9030.30
E-GEOD-98556	yes	7801.62
E-MTAB-10042	yes	5462.70
E-CURD-112	yes	5051.65
E-HCAD-4	yes	4193.64
E-HCAD-10	yes	4185.99
E-MTAB-6701	yes	4154.47
E-MTAB-7407	yes	4067.80
E-MTAB-8221	yes	3860.30
E-HCAD-6	yes	3343.68
E-MTAB-9067	yes	3216.50
E-MTAB-9906	yes	3007.96
E-MTAB-10662	yes	2782.89
E-CURD-85	yes	2699.87
E-MTAB-10432	yes	2595.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CREB1, E2F1, E2F4, EGR1, JUN, KLF10, LYL1, MYC, NFKB, RARA, SP3, SPDEF, STAT3, TAL1, TCF3, TFDP1, TP53, TP73, ZNF699

miRNA regulators (miRDB)

75 targeting STMN1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3609	99.52	69.89	2587

Literature-anchored findings (GeneRIF, showing 40)

• Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer’s disease. (PMID:11771751)
• Inhibition of heat-induced phosphorylation of stathmin by the bioflavonoid quercetin (PMID:11870780)
• Oncoprotein 18 levels and phosphorylation mediate megakaryocyte polyploidization in human erythroleukemia cells (PMID:11922601)
• the somatic mutation identified in Op18 has profound effects on cell homeostasis that may lead to tumorigenicity (PMID:12242154)
• The overexpression of this protein in poorly differentiated lung adenocarcinomas and the elevated expression of the phosphorylated forms may offer a new target for drug- or gene-directed therapy and may have potential utility as a tumor marker. (PMID:12644570)
• stathmin expression is necessary for the proliferation and differentiation of early megakaryoblasts and its suppression in the later stages of megakaryocytic maturation is necessary for polyploidization. (PMID:12763137)
• stathmin does not work as a pH-sensitive protein as shown by thermodynamic studies (PMID:12860982)
• We report the increased expression of stathmin, a developmentally regulated tubulin-binding protein, in the brains of patients with multiple sclerosis (MS). (PMID:15659612)
• These observations support a model in which downregulation of stathmin expression in megakaryocytes and other polyploid cells may be a critically important factor in endomitosis and polyploidy. (PMID:16258287)
• results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for oral squamous cell carcinoma (PMID:16495930)
• provides a biophysical basis for understanding the mechanism by which local stathmin activity gradients important for promoting localized microtubule growth (PMID:16554300)
• Although Op18 is dispensable for mitosis, the hyperactive Q18–>E mutant, or overexpressed wild-type Op18, exerts aneugenic effects that are likely to contribute to chromosomal instability in tumors (PMID:16624860)
• The NF-Y site at -65 accounts for greater than 60% of the Op18 gene expression. (PMID:16757134)
• Stathmin repression selectively induces certain tumor-suppressor functions in cancer cells with mutant p53, including cell cycle arrest and apoptosis. (PMID:16909102)
• Survivin gene promoter-driven stathmin siRNA expression vector may have potential use in tumor gene therapy with targeted tumor gene silencing effect. (PMID:17012855)
• The current structural and thermodynamic studies on the tubulin-stathmin interaction were summarized. (PMID:17029844)
• Loss of heterozygosity for the stathmin gene may be associated with improved outcomes of patients with chromosome 1 anaplastic oligodendroglioma tumors. (PMID:17440165)
• Stathmin expression is highest when the prostate is undergoing morphogenesis or tumorigenesis and these processes may be regulated through differential phosphorylation. (PMID:17455228)
• This study suggests that Epstein-Barr virus infection induces STMN1 expression, which play a role in cell cycle progression and proliferation in the human B lymphocyte. (PMID:17472732)
• Overexpression of stathmin is an early protumorigenic event in human hepatocarcinogenesis, and its up-regulation can be mediated by gain-of-function mutations in p53. (PMID:17663418)
• STMN1, but not SYK or S100A2, have roles in preventing progression of ER-positive primary breast cancer (PMID:17874182)
• Results showed that the stathmin mRNA expression was detected in all the ovarian carcinoma tissue samples and those samples with metastasis had higher levels of stathmin mRNA expression in initial biopsy specimens. (PMID:18054374)
• Depletion of Op18 by means of RNA interference increased the susceptibility of tubulin to TBCE or E-like mediated disruption, while overexpressed Op18 exerted a tubulin-protective effect. (PMID:18262179)
• Stathmin plays a significant role in tumor metastasis formation. (PMID:18305103)
• Op18 mediates posttranscriptional regulation of tubulin mRNA in Jurkat cells through the same basic autoregulatory mechanism as microtubule-poisoning drugs (PMID:18434595)
• stathmin is probably not useful as a stand-alone marker to determine malignancy in pheochromocytomas for individual tumors (PMID:18461287)
• substantial reduction in STMN1 was deminstrated upon restoration of miR-223 expression in hepatocellular cell lines (PMID:18555017)
• Genes more highly expressed in BRCA1-associated tumors included stathmin, osteopontin, TGFbeta2 and Jagged 1 (PMID:18563556)
• Data found the ratio of MAP4 to stathmin mRNA was found to be higher in diseased lung tissues compared to normal lung tissues, suggesting this ratio might also be used as a clinically relevant biomarker for NSCLCs. (PMID:18613117)
• The expression levels of stathmin gene and protein were significantly higher in laryngeal squamous cell carcinoma than those in normal laryngeal tissues. (PMID:18666697)
• Stathmin expression may be closely associated with early trophoblast migration and differentiation into syncytiotrophoblasts during placentation. (PMID:18718898)
• The rs182455 polymorphism of stathmin does not influence multiple sclerosis susceptibility or clinical disease course. (PMID:19012073)
• Hyperactive melanocytes can be inhibited by altering Stathmin 1 expression. (PMID:19017487)
• Stathmin expression correlates with cervical carcinogenesis and tumor progression, and this molecule is a valuable prognostic marker in patients with cervical carcinoma. (PMID:19034510)
• LMP1 regulates Op18/stathmin signaling by cdc2 mediation. (PMID:19048596)
• Endometrial stathmin is linked to HIF-1alpha protein accumulation and VEGF expression through the PI3K/Akt signaling pathway and may be involved in regeneration of the endometrium during the menstrual cycle in human uterine cells. (PMID:19179443)
• overexpression of stathmin was seen for all malignant pheochromocytomas studied and for the metastasis compared to the benign tumors (PMID:19449284)
• that STMN1 genotype interacting with individuals’ gender significantly impacts fear and anxiety responses as measured with the startle and cortisol stress response (PMID:19526456)
• Stathmin 1 is associated with receptivity in the human endometrium. (PMID:19556289)
• High stathmin expression correlates with tumor dissemination, is an important prognostic factor of medulloblastoma, and may serve as a useful marker for more intensive adjuvant therapies. (PMID:19569914)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stmn1a	ENSDARG00000004169
danio_rerio	stmn1b	ENSDARG00000033655
mus_musculus	Stmn1	ENSMUSG00000028832
rattus_norvegicus	LOC102546674	ENSRNOG00000022375
drosophila_melanogaster	stai	FBGN0266521

Paralogs (4): STMN4 (ENSG00000015592), STMN2 (ENSG00000104435), STMN3 (ENSG00000197457), STMND1 (ENSG00000230873)

Protein

Protein identifiers

Stathmin — P16949 (reviewed: P16949)

Alternative names: Leukemia-associated phosphoprotein p18, Metablastin, Oncoprotein 18, Phosphoprotein p19, Prosolin, Protein Pr22, pp17

All UniProt accessions (3): A0A140VJW2, A2A2D0, P16949

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Phosphorylation at Ser-16 may be required for axon formation during neurogenesis. Involved in the control of the learned and innate fear.

Subunit / interactions. Binds to two alpha/beta-tubulin heterodimers. Interacts with KIST.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitous. Expression is strongest in fetal and adult brain, spinal cord, and cerebellum, followed by thymus, bone marrow, testis, and fetal liver. Expression is intermediate in colon, ovary, placenta, uterus, and trachea, and is readily detected at substantially lower levels in all other tissues examined. Lowest expression is found in adult liver. Present in much greater abundance in cells from patients with acute leukemia of different subtypes than in normal peripheral blood lymphocytes, non-leukemic proliferating lymphoid cells, bone marrow cells, or cells from patients with chronic lymphoid or myeloid leukemia.

Post-translational modifications. Many different phosphorylated forms are observed depending on specific combinations among the sites which can be phosphorylated. MAPK is responsible for the phosphorylation of stathmin in response to NGF. Phosphorylation at Ser-16 seems to be required for neuron polarization. Phosphorylation at Ser-63 reduces tubulin binding 10-fold and suppresses the MT polymerization inhibition activity.

Induction. Down-regulated in response to enterovirus 71 (EV71) infection (at protein level).

Similarity. Belongs to the stathmin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P16949-1	1	yes
P16949-2	2

RefSeq proteins (4): NP_001138926, NP_005554, NP_981944, NP_981946 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000956	Stathmin_fam	Family
IPR030514	Stathmin_CS	Conserved_site
IPR036002	Stathmin_sf	Homologous_superfamily

Pfam: PF00836

UniProt features (18 total): modified residue 11, initiator methionine 1, chain 1, splice variant 1, domain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16949-F1	88.59	0.72

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 (11): 25, 29, 31, 38, 63, 100, 119, 2, 4, 9, 16

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-1236394	Signaling by ERBB4
R-HSA-162582	Signal Transduction
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 585 (showing top): GOBP_MITOTIC_CYTOKINESIS, E2F_Q4, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, MORF_DNMT1, MODULE_52, E2F_Q4_01, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_169, E2F4DP1_01, PAL_PRMT5_TARGETS_UP, MODULE_151, CROONQUIST_NRAS_SIGNALING_DN, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (19): mitotic cytokinesis (GO:0000281), microtubule depolymerization (GO:0007019), mitotic spindle organization (GO:0007052), signal transduction (GO:0007165), axonogenesis (GO:0007409), response to virus (GO:0009615), regulation of cell migration (GO:0030334), regulation of microtubule polymerization or depolymerization (GO:0031110), negative regulation of microtubule polymerization (GO:0031115), neuron projection development (GO:0031175), intracellular signal transduction (GO:0035556), hepatocyte growth factor receptor signaling pathway (GO:0048012), nervous system development (GO:0007399), cell differentiation (GO:0030154), negative regulation of Rho protein signal transduction (GO:0035024), negative regulation of stress fiber assembly (GO:0051497), establishment of skin barrier (GO:0061436), negative regulation of thrombin-activated receptor signaling pathway (GO:0070495), negative regulation of guanyl-nucleotide exchange factor activity (GO:1905098)

GO Molecular Function (2): tubulin binding (GO:0015631), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), membrane (GO:0016020), neuron projection (GO:0043005), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by ERBB4	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mitotic cell cycle	2
microtubule polymerization or depolymerization	2
intracellular anatomical structure	2
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
protein depolymerization	1
supramolecular fiber organization	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
response to other organism	1
cell migration	1
regulation of cell motility	1
regulation of microtubule cytoskeleton organization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
negative regulation of protein polymerization	1
microtubule polymerization	1
negative regulation of supramolecular fiber organization	1
neuron development	1
plasma membrane bounded cell projection organization	1
signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
system development	1
cellular developmental process	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
skin epidermis development	1

Protein interactions and networks

STRING

3660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STMN1	STAT3	P40763	937
STMN1	UHMK1	Q8TAS1	910
STMN1	CDKN1B	P46527	899
STMN1	MAP4	P27816	726
STMN1	RB1CC1	Q8TDY2	715
STMN1	TTL	Q8NG68	696
STMN1	TP53	P04637	682
STMN1	TNFRSF6B	O95407	670
STMN1	RHOA	P06749	634
STMN1	KIF2C	Q99661	627
STMN1	CLIP1	P30622	616
STMN1	CDC42	P21181	612
STMN1	TSG101	Q99816	602
STMN1	U2AF2	P26368	593
STMN1	MAPT	P10636	570

IntAct

94 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CDKN1B	STMN1	psi-mi:“MI:0915”(physical association)	0.590
SESTD1	STMN1	psi-mi:“MI:0915”(physical association)	0.560
STMN1	SESTD1	psi-mi:“MI:0915”(physical association)	0.560
STMN2	MTA2	psi-mi:“MI:0914”(association)	0.530
STMN1	TUBA4A	psi-mi:“MI:0403”(colocalization)	0.500
TUBA4A	STMN1	psi-mi:“MI:0915”(physical association)	0.500
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
STMN1	NSF	psi-mi:“MI:0915”(physical association)	0.400
	STMN1	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	STMN1	psi-mi:“MI:0915”(physical association)	0.370
GLP1R	STMN1	psi-mi:“MI:0915”(physical association)	0.370
SEPTIN2	STMN1	psi-mi:“MI:0915”(physical association)	0.370
STMN1	CHEK2	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
FOSL2	RECQL5	psi-mi:“MI:0914”(association)	0.350
HSPA5	NCOR2	psi-mi:“MI:0914”(association)	0.350
CDKN3	STMN1	psi-mi:“MI:0914”(association)	0.350
PHOSPHO1	DDX39A	psi-mi:“MI:0914”(association)	0.350
DUSP22	ACACB	psi-mi:“MI:0914”(association)	0.350
STAT1	KPNA6	psi-mi:“MI:0914”(association)	0.350
HSPA8	PPP6C	psi-mi:“MI:0914”(association)	0.350

BioGRID (264): STMN1 (Affinity Capture-MS), SESTD1 (Two-hybrid), STMN1 (Two-hybrid), STMN1 (Affinity Capture-Western), SIVA1 (Affinity Capture-Western), SIVA1 (Reconstituted Complex), STMN1 (Biochemical Activity), AHNAK (Co-fractionation), DUT (Co-fractionation), HN1 (Co-fractionation), HN1L (Co-fractionation), IMPA2 (Co-fractionation), MYO1E (Co-fractionation), NUDCD2 (Co-fractionation), PFDN2 (Co-fractionation)

ESM2 similar proteins: A4IFK9, A4IGK3, A6H6W9, A9YWH3, O54941, O70166, O93388, P13668, P16949, P21818, P31395, P54227, P55821, P63042, P63043, Q2KI04, Q32KT0, Q32M00, Q3SZ60, Q3T0C7, Q4R4N5, Q4R712, Q5BJU6, Q5R4C5, Q5R8C6, Q5RBB8, Q5RE12, Q5SQY2, Q5XIA2, Q5ZK25, Q642H2, Q6AYJ2, Q6DUB7, Q6I9Y2, Q6NXN1, Q6PH81, Q7TMY4, Q7Z422, Q8BR65, Q8CJ19

Diamond homologs: A4IFK9, A9YWH3, O70166, O93388, P13668, P16949, P21818, P31395, P54227, P55821, P63042, P63043, Q09001, Q09002, Q09004, Q09005, Q09006, Q3T0C7, Q4R4N5, Q4R712, Q5R4C5, Q5R8C6, Q6DUB7, Q90987, Q93045, Q9H169, Q9JHU6, Q9NZ72

SIGNOR signaling

34 interactions.

A	Effect	B	Mechanism
PAK1	down-regulates	STMN1	phosphorylation
CAMK2A	down-regulates	STMN1	phosphorylation
CDK5	down-regulates	STMN1	phosphorylation
MAPK1	down-regulates	STMN1	phosphorylation
MAPK10	down-regulates	STMN1	phosphorylation
MAPK8	down-regulates	STMN1	phosphorylation
MAPK9	down-regulates	STMN1	phosphorylation
UHMK1	down-regulates	STMN1	phosphorylation
STMN1	down-regulates	TTL	binding
MAPK3	“down-regulates activity”	STMN1	phosphorylation
MAPK13	down-regulates	STMN1	phosphorylation
JNK	down-regulates	STMN1	phosphorylation
Gbeta	“down-regulates activity”	STMN1	phosphorylation
ERK1/2	“down-regulates activity”	STMN1	phosphorylation
AURKA	“down-regulates activity”	STMN1	phosphorylation
CDK1	“up-regulates activity”	STMN1	phosphorylation
PAK4	“down-regulates activity”	STMN1	phosphorylation
PRKCB	down-regulates	STMN1	phosphorylation
CAMK4	down-regulates	STMN1	phosphorylation
PRKACA	down-regulates	STMN1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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
Aggrephagy	5	17.0×	1e-03
PKR-mediated signaling	8	15.4×	2e-05
Antimicrobial mechanism of IFN-stimulated genes	5	13.5×	2e-03
Autophagy	5	10.2×	5e-03
Interferon Signaling	6	9.9×	2e-03
mRNA Polyadenylation	7	8.4×	2e-03
Macroautophagy	5	7.9×	9e-03
COPI-dependent Golgi-to-ER retrograde traffic	5	7.6×	9e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

774 predictions. Top by Δscore:

Variant	Effect	Δscore
1:25901083:TTATC:T	acceptor_gain	1.0000
1:25901084:TATC:T	acceptor_gain	1.0000
1:25901085:ATC:A	acceptor_gain	1.0000
1:25901085:ATCC:A	acceptor_loss	1.0000
1:25901086:TC:T	acceptor_gain	1.0000
1:25901087:CC:C	acceptor_gain	1.0000
1:25901087:CCTG:C	acceptor_loss	1.0000
1:25901088:C:CC	acceptor_gain	1.0000
1:25901486:CCAA:C	donor_loss	1.0000
1:25901487:CAAC:C	donor_loss	1.0000
1:25901488:AACCT:A	donor_loss	1.0000
1:25901489:A:AC	donor_gain	1.0000
1:25901490:C:CC	donor_gain	1.0000
1:25901490:CCTT:C	donor_gain	1.0000
1:25901493:T:A	donor_gain	1.0000
1:25901507:T:A	donor_gain	1.0000
1:25901552:T:TA	donor_gain	1.0000
1:25901678:TGGGA:T	acceptor_gain	1.0000
1:25901679:GGGA:G	acceptor_gain	1.0000
1:25901680:GGA:G	acceptor_gain	1.0000
1:25901681:GA:G	acceptor_gain	1.0000
1:25901683:C:CC	acceptor_gain	1.0000
1:25901090:G:GC	acceptor_gain	0.9900
1:25903636:TTTAC:T	donor_loss	0.9900
1:25903637:TTACC:T	donor_loss	0.9900
1:25903638:TACC:T	donor_loss	0.9900
1:25903639:A:AG	donor_loss	0.9900
1:25903640:C:G	donor_loss	0.9900
1:25903814:C:CC	acceptor_gain	0.9900
1:25904660:CTACC:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000562532 (1:25895585 G>A), RS1000875160 (1:25907396 G>A,T), RS1000887262 (1:25889192 G>A), RS1000918232 (1:25889497 C>A,T), RS1000939569 (1:25906886 G>A,C), RS1000975667 (1:25900906 C>T), RS1001091984 (1:25900284 T>A), RS1001204320 (1:25906243 C>A,T), RS1001216970 (1:25887852 A>G), RS1001248162 (1:25888120 T>A), RS1001564643 (1:25900503 G>A), RS1001641030 (1:25898033 G>A), RS1001830625 (1:25898322 C>CT), RS1001935653 (1:25898542 A>G), RS1001979603 (1:25899356 G>A)

Disease associations

OMIM: gene MIM:151442 | 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: yes

ChEMBL targets (1): CHEMBL3879843 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
STMN1 EXPRESSION	Paclitaxel	Endometrial Carcinoma	Resistance	CIViC B	EID855

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs182455	STMN1		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.08	Kd	8256	nM	CHEMBL5653589
5.08	ED50	8256	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 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	2149513: Binding affinity to human STMN1 incubated for 45 mins by Kinobead based pull down assay	kd	8.2556	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	6
Estradiol	decreases expression, decreases phosphorylation, increases expression	6
sodium arsenite	affects methylation, decreases expression, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
Aflatoxin B1	decreases methylation, increases methylation, affects expression	4
Resveratrol	affects cotreatment, increases expression, decreases expression, increases phosphorylation	3
Arsenic Trioxide	increases degradation, increases reaction, decreases expression, decreases reaction, increases cleavage (+2 more)	3
Copper	affects binding, decreases expression, increases expression	3
Doxorubicin	affects expression, decreases expression, affects response to substance	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Cadmium Chloride	decreases expression, increases methylation, increases abundance, increases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
Cadmium	increases expression, increases abundance	2
Cisplatin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
propionaldehyde	decreases expression	1
baicalein	decreases expression, decreases reaction	1
chlorophyllin	decreases expression	1
geraniol	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
IMOL S-140	increases expression	1
thiodipropionic acid	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3869490	Binding	Increase in STMN1 phosphorylation in human A549 cells harboring KRAS mutant at 1 uM after 8 hrs by Western blot analysis	Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1UJ	Abcam U-87MG STMN1 KO	Cancer cell line	Male
CVCL_D8WM	Ubigene HCT 116 STMN1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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