STMN2

Summary

STMN2 (stathmin 2, HGNC:10577) is a protein-coding gene on chromosome 8q21.13, encoding Stathmin-2 (Q93045). Regulator of microtubule stability.

This gene encodes a member of the stathmin family of phosphoproteins. Stathmin proteins function in microtubule dynamics and signal transduction. The encoded protein plays a regulatory role in neuronal growth and is also thought to be involved in osteogenesis. Reductions in the expression of this gene have been associated with Down’s syndrome and Alzheimer’s disease. Alternatively spliced transcript variants have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome 6.

Source: NCBI Gene 11075 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 12 total
• GTEx eGene: eQTL in 16 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.25 (highly constrained)
• MANE Select transcript: NM_007029
• Interaction hub: 1,788 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10577
Approved symbol	STMN2
Name	stathmin 2
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	SCG10
Ensembl gene	ENSG00000104435
Ensembl biotype	protein_coding
OMIM	600621
Entrez	11075

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

MANE Select: ENST00000220876

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 1

ENST00000220876, ENST00000518111, ENST00000518491, ENST00000911966, ENST00001099952, ENST00001099953, ENST00001131000, ENST00001134868

RefSeq mRNA: 2 — MANE Select: NM_007029 NM_001199214, NM_007029

CCDS: CCDS43748, CCDS56542

Canonical transcript exons

ENST00000220876 — 5 exons

Exon	Start	End
ENSE00000909925	79641378	79641550
ENSE00001010210	79654871	79655062
ENSE00001323097	79664815	79666158
ENSE00002093744	79611117	79611214
ENSE00003660857	79636802	79636897

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 99.95.

FANTOM5 (CAGE): breadth broad, TPM avg 96.3496 / max 11167.1119, expressed in 623 samples.

Highest expression (Bgee): cortical plate, pons, cerebellar vermis, dorsal root ganglion, lateral nuclear group of thalamus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STMN2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.9e-22	+0.30	8:79357655:G:A
Testis	eqtl	8.2e-05	+0.28	8:79638588:T:G
Brain Amygdala	eqtl	4.7e-03	-0.35	8:79106468:C:T
Adipose Subcutaneous	eqtl	5.7e-03	-0.19	8:78960238:G:T
Thyroid	eqtl	6.6e-03	+0.46	8:79718628:T:C
Skin Sun Exposed Lower leg	eqtl	1.1e-02	-0.30	8:79041530:T:C
Brain Cortex	eqtl	1.4e-02	+0.82	8:78787696:G:T
Brain Nucleus accumbens basal ganglia	eqtl	1.6e-02	-0.23	8:79634974:C:T
Pancreas	eqtl	1.6e-02	-0.48	8:79341206:A:G
Brain Cerebellum	eqtl	2.4e-02	-0.32	8:79655994:G:A
Cells EBV-transformed lymphocytes	eqtl	2.6e-02	+1.84	8:78785519:A:G
Prostate	eqtl	2.7e-02	-0.59	8:80176462:TTAACAA:T
Brain Cerebellar Hemisphere	eqtl	3.3e-02	-0.27	8:79668127:A:G
Colon Sigmoid	eqtl	4.5e-02	+0.27	8:79867625:G:T
Colon Transverse	eqtl	4.9e-02	-0.26	8:79377918:G:A
Brain Hypothalamus	eqtl	4.9e-02	-0.31	8:79950829:G:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
89490	87.4369	612
89489	5.1477	299
89491	2.8896	268
89492	0.2925	97
205237	0.2137	76
89497	0.1315	44
89495	0.1197	45
89493	0.0941	50
89496	0.0239	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.95	gold quality
pons	UBERON:0000988	99.91	gold quality
cerebellar vermis	UBERON:0004720	99.89	gold quality
dorsal root ganglion	UBERON:0000044	99.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.87	gold quality
ganglionic eminence	UBERON:0004023	99.77	gold quality
substantia nigra pars compacta	UBERON:0001965	99.76	gold quality
superior vestibular nucleus	UBERON:0007227	99.74	gold quality
frontal pole	UBERON:0002795	99.73	gold quality
cerebellar cortex	UBERON:0002129	99.69	gold quality
cerebellum	UBERON:0002037	99.68	gold quality
cerebellar hemisphere	UBERON:0002245	99.68	gold quality
paraflocculus	UBERON:0005351	99.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.64	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.61	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.60	gold quality
middle temporal gyrus	UBERON:0002771	99.54	gold quality
orbitofrontal cortex	UBERON:0004167	99.48	gold quality
superior frontal gyrus	UBERON:0002661	99.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.28	gold quality
frontal cortex	UBERON:0001870	99.25	gold quality
frontal lobe	UBERON:0016525	99.25	gold quality
ventral tegmental area	UBERON:0002691	99.20	gold quality
prefrontal cortex	UBERON:0000451	99.17	gold quality
right frontal lobe	UBERON:0002810	99.17	gold quality
occipital lobe	UBERON:0002021	99.13	gold quality
neocortex	UBERON:0001950	99.11	gold quality
parietal lobe	UBERON:0001872	99.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.09	gold quality
primary visual cortex	UBERON:0002436	99.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.03	gold quality
cerebral cortex	UBERON:0000956	99.01	gold quality
endothelial cell	CL:0000115	98.98	gold quality
postcentral gyrus	UBERON:0002581	98.97	gold quality
lateral globus pallidus	UBERON:0002476	98.83	gold quality
hypothalamus	UBERON:0001898	98.81	gold quality
cingulate cortex	UBERON:0003027	98.75	gold quality
anterior cingulate cortex	UBERON:0009835	98.74	gold quality
entorhinal cortex	UBERON:0002728	98.65	gold quality
temporal lobe	UBERON:0001871	98.49	gold quality
medulla oblongata	UBERON:0001896	98.49	gold quality
amygdala	UBERON:0001876	98.35	gold quality
telencephalon	UBERON:0001893	98.32	gold quality
middle frontal gyrus	UBERON:0002702	98.32	gold quality
Ammon’s horn	UBERON:0001954	98.26	gold quality
trigeminal ganglion	UBERON:0001675	97.99	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.82	gold quality
midbrain	UBERON:0001891	97.81	gold quality
substantia nigra	UBERON:0002038	97.67	gold quality
nucleus accumbens	UBERON:0001882	97.45	gold quality
CA1 field of hippocampus	UBERON:0003881	97.34	gold quality
putamen	UBERON:0001874	97.18	gold quality
brain	UBERON:0000955	97.05	gold quality
central nervous system	UBERON:0001017	96.90	gold quality
caudate nucleus	UBERON:0001873	96.89	gold quality
forebrain	UBERON:0001890	96.60	gold quality
adult organism	UBERON:0007023	96.56	gold quality
ventricular zone	UBERON:0003053	95.60	gold quality
islet of Langerhans	UBERON:0000006	95.17	gold quality
inferior olivary complex	UBERON:0002127	93.88	gold quality
embryo	UBERON:0000922	93.51	gold quality
spinal cord	UBERON:0002240	92.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.90	gold quality
rectum	UBERON:0001052	91.86	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.69	gold quality
globus pallidus	UBERON:0001875	90.10	gold quality
corpus callosum	UBERON:0002336	88.48	gold quality
colonic epithelium	UBERON:0000397	88.41	gold quality
medial globus pallidus	UBERON:0002477	88.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.41	gold quality
inferior vagus X ganglion	UBERON:0005363	86.41	gold quality
sigmoid colon	UBERON:0001159	85.99	gold quality
large intestine	UBERON:0000059	85.06	gold quality
colon	UBERON:0001155	84.90	gold quality
transverse colon	UBERON:0001157	84.86	gold quality
sympathetic trunk	UBERON:0000407	84.09	gold quality
intestine	UBERON:0000160	83.75	gold quality
sperm	CL:0000019	83.14	silver quality
adrenal tissue	UBERON:0018303	82.72	gold quality
caecum	UBERON:0001153	82.37	gold quality
subthalamic nucleus	UBERON:0001906	82.02	gold quality
male germ cell	CL:0000015	81.60	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.41	gold quality
vermiform appendix	UBERON:0001154	80.58	gold quality
vena cava	UBERON:0004087	80.02	gold quality
type B pancreatic cell	CL:0000169	79.62	silver quality
mucosa of transverse colon	UBERON:0004991	79.58	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.42	gold quality
small intestine	UBERON:0002108	78.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.93	gold quality
colonic mucosa	UBERON:0000317	77.33	gold quality
pancreas	UBERON:0001264	77.32	gold quality
duodenum	UBERON:0002114	77.22	gold quality
pituitary gland	UBERON:0000007	76.55	gold quality
adenohypophysis	UBERON:0002196	76.35	gold quality
skin of hip	UBERON:0001554	74.44	gold quality
skin of leg	UBERON:0001511	74.17	gold quality
mucosa of stomach	UBERON:0001199	73.83	gold quality
fundus of stomach	UBERON:0001160	73.70	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	9573.66
E-MTAB-8894	yes	8576.52
E-MTAB-11121	yes	6766.63
E-MTAB-8221	yes	5231.44
E-HCAD-5	yes	4802.35
E-MTAB-10485	yes	4601.98
E-HCAD-25	yes	4075.21
E-MTAB-7316	yes	4016.20
E-GEOD-98556	yes	3700.91
E-GEOD-75140	yes	3248.36
E-GEOD-93593	yes	2660.42
E-MTAB-6911	yes	2240.04
E-MTAB-6108	yes	2097.98
E-HCAD-35	yes	1319.08
E-HCAD-31	yes	1012.96

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 69 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Postcentral gyrus	tissue	1162.6
Pons	tissue	802.0
Spinal cord	tissue	658.7
Prefrontal cortex	tissue	644.3
Cerebral cortex	tissue	644.3
Cerebellum	tissue	634.8
Occipital cortex	tissue	630.2
Somatosensory cortex	tissue	627.3
Motor cortex	tissue	619.1
Locus coeruleus	tissue	613.4
Hippocampal formation	tissue	592.4
Thalamus	tissue	591.4
Retrosplenial and cingulate cortex	tissue	575.8
Retrosplenial cortex	tissue	567.0
Substantia nigra	tissue	566.6
Superior colliculi	tissue	558.6
Entorhinal cortex	tissue	556.4
Temporal cortex	tissue	549.9
Medulla oblongata	tissue	542.0
Hypothalamus	tissue	536.5
Frontal cortex	tissue	481.5
Midbrain	tissue	479.9
Insular cortex	tissue	463.6
Periaqueductal gray	tissue	427.1
Amygdala	tissue	382.9
Septum	tissue	358.7
Ventral forebrain	tissue	277.6
Olfactory bulb	tissue	254.5
Hippocampus	tissue	194.1
Caudate putamen	tissue	184.1
Putamen	tissue	179.6
Basal ganglia	tissue	168.4
Nucleus accumbens	tissue	114.3
Retina	tissue	80.5
Corpus callosum	tissue	74.5
Adrenal gland	tissue	64.6
Rectum	tissue	27.1
Colon	tissue	20.6
Small intestine	tissue	17.4
Duodenum	tissue	13.1
Choroid plexus	tissue	12.9
Skin 1	tissue	10.9
Appendix	tissue	9.1
Pituitary gland	tissue	8.4
Cervix	tissue	7.9
Smooth muscle	tissue	5.9
Vagina	tissue	4.5
Pancreas	tissue	4.4
Spleen	tissue	4.2
Gallbladder	tissue	3.3
Breast	tissue	2.6
Stomach 1	tissue	2.5
Prostate	tissue	2.4
Testis	tissue	1.7
Seminal vesicle	tissue	1.6
Tonsil	tissue	1.3
Adipose tissue	tissue	1.0
Endometrium 1	tissue	1.0
Esophagus	tissue	0.9
Salivary gland	tissue	0.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral hypothalamic area (804.1), Ventral spinal cord (658.7), Arcuate nucleus (647.9), Subiculum (592.4), Precentral gyrus (529.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, CTNNBIP1, EBF1, HNF4A, JUN, REST

miRNA regulators (miRDB)

Targeting STMN2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 112 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-552-5P	99.93	68.56	1583

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.25, missense Z 2.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000220876 — one region, missense o/e 0.53.

Literature-anchored findings (GeneRIF, showing 24)

• RGS6 interacts with this protein and promotes neuronal differentiation; role of the G gamma subunit-like (GGL) domain of RGS6 (PMID:12140291)
• STMN2 is required for maintaining the anchorage-independent growth state of beta-catenin/TCF-activated hepatoma cells (PMID:16712787)
• activity at opposite microtubule ends may play role role in regulating growth cone microtubules; ability to promote plus end growth may facilitate microtubule extension; ability to destabilize minus ends may provide tubulin for net plus end elongation (PMID:17311410)
• Review proposes a model reconciling the microtubule regulatory properties of superior cervical ganglion protein 10 with its role as a c-Jun N-terminal kinase 1 (JNK1) effector of regeneration. (PMID:18076368)
• BRI3 associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells. (PMID:18452648)
• SCLIP and SCG10 were colocalized to the Golgi apparatus of chromaffin cells in vivo and shared localization with CHGA as it transited the Golgi. (PMID:18549247)
• STMN2 appears a novel marker of osteogenesis and osteoblast per se, that could play a role in the regulation of the adipocyte/osteoblast balance. (PMID:18611392)
• SCG10 acts as an effector downstream of Rnd1 to regulate axon extensions by modulating microtubule organization. (PMID:18996843)
• Overexpression of SCG10 is associated with Liver Fibrosis. (PMID:20802173)
• CaMy1 via SCG10 couples Ca(2+) signals with the dynamics of microtubules during neuronal outgrowth in the developing brain. (PMID:21215777)
• SCG10 is upregulated in the IKAP/Elp1-deficient familial dysautonomia cerebrum lending support to the concept that SCG10 elevation can alter the microtubule organization and dynamics (PMID:21273291)
• PAK4-SCG10 signaling occurs in gastric cancer cell invasion. (PMID:23893240)
• RARB and STMN2 polymorphisms were not associated with sporadic CJD in the Korean population. (PMID:24414001)
• STMN and SCG10 are similarly targeted by JNK but there are clear differences in JNK recognition and phosphorylation of the closely related family member, SCLIP. (PMID:24589734)
• expression of STMN2, which encodes a microtubule regulator, declined after TDP-43 knockdown and TDP-43 mislocalization as well as in patient-specific motor neurons and postmortem patient spinal cord. STMN2 loss upon reduced TDP-43 function was due to altered splicing, which is functionally important, as we show STMN2 is necessary for normal axonal outgrowth and regeneration. (PMID:30643292)
• premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability. (PMID:30643298)
• STMN2 is a key regulator functionally connected to known Parkinson’s disease risk genes. Network analysis predicts a function of human STMN2 in synaptic trafficking. [Meta-Analysis} (PMID:31748532)
• Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia. (PMID:32790644)
• STMN2 mediates nuclear translocation of Smad2/3 and enhances TGFbeta signaling by destabilizing microtubules to promote epithelial-mesenchymal transition in hepatocellular carcinoma. (PMID:33705863)
• NEK1 and STMN2 short tandem repeat lengths are not associated with Australian amyotrophic lateral sclerosis risk. (PMID:35613520)
• Analysis of STMN2 CA repeats in italian ALS patients shows no association. (PMID:35876065)
• STMN2 overexpression promotes cell proliferation and EMT in pancreatic cancer mediated by WNT/beta-catenin signaling. (PMID:36460804)
• TDP43 blocks misprocessing of STMN2 RNA. (PMID:37012364)
• Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer’s disease. (PMID:38175301)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stmn2a	ENSDARG00000033234
danio_rerio	stmn2b	ENSDARG00000070537
mus_musculus	Stmn2	ENSMUSG00000027500
rattus_norvegicus	Stmn2	ENSRNOG00000011705
drosophila_melanogaster	stai	FBGN0266521

Paralogs (4): STMN4 (ENSG00000015592), STMN1 (ENSG00000117632), STMN3 (ENSG00000197457), STMND1 (ENSG00000230873)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98241) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal motor neuron innervation pattern	1
abnormal neuromuscular synapse morphology	1
abnormal phrenic nerve morphology	1
hyperactivity	1
impaired coordination	1
unresponsive to tactile stimuli	1
infertility	1
abnormal neuron morphology	1
delayed axon extension	1
abnormal synaptic vesicle number	1
abnormal action potential	1
abnormal axon morphology	1
abnormal neurite morphology	1
abnormal synaptic bouton morphology	1
decreased total body fat amount	1
decreased grip strength	1
perinatal lethality, incomplete penetrance	1
preweaning lethality, incomplete penetrance	1
abnormal mitochondrial shape	1
abnormal microtubule cytoskeleton morphology	1
increased mechanical nociceptive threshold	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gekko japonicus	A9YWH3	100.0%	Diamond
Bos taurus	Q3T0C7	100.0%	Diamond
Macaca fascicularis	Q4R712	100.0%	Diamond
Pongo abelii	Q5R4C5	100.0%	Diamond
Sus scrofa	Q6DUB7	100.0%	Diamond
Gallus gallus	Q90987	96.6%	Diamond
Xenopus laevis	Q09001	90.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR12123	ncRNA	113219456
LINC01607	ncRNA	101927067
HEY1	protein-coding	23462

Protein

Protein identifiers

Stathmin-2 — Q93045 (reviewed: Q93045)

Alternative names: Superior cervical ganglion-10 protein

All UniProt accessions (2): E5RGX5, Q93045

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone.

Subunit / interactions. Interacts with MAPK8. Interacts with ITM2C. Interacts with KIFBP. Interacts (via the N-terminal region) with CIB1 (via C-terminal region); the interaction is direct, occurs in a calcium-dependent manner and attenuates the neurite outgrowth inhibition of STMN2.

Subcellular location. Cytoplasm. Perinuclear region. Cell projection. Growth cone. Membrane. Axon. Golgi apparatus. Endosome. Lamellipodium.

Tissue specificity. Neuron specific.

Post-translational modifications. Sumoylated. Phosphorylated mostly by MAPK8, but also by MAPK9 and MAPK10 in the developing brain cortex. N-terminal palmitoylation promotes specific anchoring to the cytosolic leaflet of Golgi membranes and subsequent vesicular trafficking along dendrites and axons. Neuronal Stathmins are substrates for palmitoyltransferases ZDHHC3, ZDHHC7 and ZDHHC15.

Similarity. Belongs to the stathmin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q93045-1	1	yes
Q93045-2	2

RefSeq proteins (2): NP_001186143, NP_008960* (*=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 (15 total): modified residue 5, lipid moiety-binding region 2, sequence conflict 2, region of interest 2, chain 1, domain 1, splice variant 1, coiled-coil region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93045-F1	85.95	0.57

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; endoplasmic reticulum

Antibody reliability (HPA): IF approved

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 (7)

Type	Positions
S-palmitoyl cysteine	22, 24
Phosphoserine	16, 50, 62, 73, 97

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9696273	RND1 GTPase cycle	curated
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 284 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, GCANCTGNY_MYOD_Q6, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, TATTATA_MIR374, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (9): microtubule depolymerization (GO:0007019), negative regulation of microtubule depolymerization (GO:0007026), positive regulation of neuron projection development (GO:0010976), negative regulation of neuron projection development (GO:0010977), regulation of microtubule polymerization or depolymerization (GO:0031110), negative regulation of microtubule polymerization (GO:0031115), positive regulation of microtubule depolymerization (GO:0031117), neuron projection development (GO:0031175), cellular response to nerve growth factor stimulus (GO:1990090)

GO Molecular Function (3): tubulin binding (GO:0015631), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (11): cytoplasm (GO:0005737), endosome (GO:0005768), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), lamellipodium (GO:0030027), growth cone (GO:0030426), neuron projection (GO:0043005), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), axon (GO:0030424)

Reactome top-level categories

4 top-level categories:

Category	Pathways
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

40 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
microtubule polymerization or depolymerization	2
microtubule depolymerization	2
negative regulation of microtubule polymerization or depolymerization	2
regulation of microtubule depolymerization	2
negative regulation of supramolecular fiber organization	2
regulation of neuron projection development	2
neuron projection development	2
endomembrane system	2
plasma membrane bounded cell projection	2
protein depolymerization	1
supramolecular fiber organization	1
negative regulation of protein depolymerization	1
positive regulation of cell projection organization	1
negative regulation of cell projection organization	1
regulation of microtubule cytoskeleton organization	1
regulation of microtubule polymerization	1
negative regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of microtubule polymerization or depolymerization	1
positive regulation of protein depolymerization	1
positive regulation of supramolecular fiber organization	1
neuron development	1
plasma membrane bounded cell projection organization	1
cellular response to growth factor stimulus	1
response to nerve growth factor	1
cytoskeletal protein binding	1
calcium ion binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1
cell leading edge	1
site of polarized growth	1
distal axon	1
somatodendritic compartment	1
cell body	1
neuron projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to nerve growth factor stimulus	BP	direct assay
negative regulation of microtubule depolymerization	BP	direct assay
negative regulation of microtubule polymerization	BP	direct assay
negative regulation of neuron projection development	BP	direct assay
positive regulation of microtubule depolymerization	BP	direct assay
positive regulation of neuron projection development	BP	direct assay
cytoplasm	CC	direct assay
growth cone	CC	direct assay
lamellipodium	CC	direct assay
neuron projection	CC	direct assay
neuronal cell body	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
calcium-dependent protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,788 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STMN2	REST	Q13127	725
STMN2	TRPC5	Q9UL62	665
STMN2	GAP43	P17677	573
STMN2	UNC13A	Q9UPW8	570
STMN2	TARDBP	Q13148	568
STMN2	VPS26C	O14972	552
STMN2	SLC32A1	Q9H598	540
STMN2	SYN1	P17600	535
STMN2	SOX2	P48431	529
STMN2	SNAP25	P13795	522
STMN2	NMNAT2	Q9BZQ4	516
STMN2	CRELD1	Q96HD1	510
STMN2	PSMG1	O95456	510
STMN2	SCN2A	Q99250	509
STMN2	ACTL6B	O94805	495

IntAct

Human interaction partners of STMN2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

Partner	Interaction type	MIscore	Records
TEX11	physical association	0.700	8
TXLNA	physical association	0.670	4
SESTD1	physical association	0.670	3
CIB1	colocalization	0.660	8
CCHCR1	physical association	0.560	3
CTNNA3	physical association	0.560	3
FAM90A1	physical association	0.560	3
MBD3	physical association	0.560	3
NTAQ1	physical association	0.560	3
PSMB1	physical association	0.560	3
TFCP2	physical association	0.560	3
MTA2	association	0.530	2
DHRS2	physical association	0.400	1
CCDC85A	physical association	0.370	1
CEP70	physical association	0.370	1
ERBB2	physical association	0.370	1
GCNT1	physical association	0.370	1
GPRASP2	physical association	0.370	1
NGFR	physical association	0.370	1
PTCHD1	physical association	0.370	1
VPS26C	association	0.350	1
EEF1A1	physical association	0.000	1
VOPP1	physical association	0.000	1

BioGRID (104 interactions; top human partners by supporting records): STMN1 (Affinity Capture-MS; 8 records), TEX11 (Two-hybrid; 5 records), FANCC (Two-hybrid; 2 records), MBD3 (Two-hybrid; 2 records), RGS6 (Two-hybrid; 2 records), AHCYL1 (Co-fractionation), AMFR (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ATP5B (Cross-Linking-MS (XL-MS)), BAD (Proximity Label-MS), C16orf62 (Affinity Capture-MS), CCDC22 (Affinity Capture-MS), CCDC85A (Two-hybrid), CCDC93 (Affinity Capture-MS)

SIGNOR signaling

showing 3 of 6 signaling interactions:

A	Effect	B	Mechanism
MAPK10	down-regulates	STMN2	phosphorylation
MAPK3	“down-regulates activity”	STMN2	phosphorylation
PRKACA	“down-regulates activity”	STMN2	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for STMN2: 12 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 504):

Position(s)	Effect	Δscore	Sites
8:79636898–79636899	donor_loss	1.0000	5
8:79641540	donor_gain	1.0000
8:79641551–79641552	donor_loss	1.0000	4
8:79654869–79654870	acceptor_loss	1.0000	6
8:79655013	donor_gain	1.0000
8:79611215–79611216	donor_loss	0.9900	6
8:79636800–79636801	acceptor_loss	0.9900	6
8:79641370	acceptor_gain	0.9900
8:79641376–79641377	acceptor_loss	0.9900	4
8:79641551	donor_loss	0.9900

AlphaMissense

533 missense substitutions predicted likely pathogenic (of 1,177 scored), across 133 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F54	8	0.956	1.000
H112	8	0.913	0.995
F127	7	0.990	0.999
C24	7	0.984	0.998
C22	7	0.981	0.998
E55	7	0.949	0.987
H163	7	0.946	0.992
M139	7	0.926	0.965
R110	7	0.923	0.994
E14	7	0.920	0.979
E99	7	0.910	0.980
E113	7	0.843	0.964
S128	7	0.827	0.958
N124	7	0.816	0.958
N145	7	0.697	0.896
G51	6	0.994	0.999
R94	6	0.991	0.999
R95	6	0.983	0.999
V167	6	0.979	0.991
K138	6	0.976	0.995

HPA cancer prognostics

RNA cancer specificity: Group enriched (Glioblastoma Multiforme, Pancreatic Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000574

Disease associations

OMIM: gene MIM:600621 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST000294_1	Creutzfeldt-Jakob disease	6e-8
GCST002868_12	Response to serotonin reuptake inhibitors in major depressive disorder	9e-7
GCST009391_1176	Metabolite levels	9e-7
GCST006149_5	Frontotemporal dementia with GRN mutation (age at onset)	4e-6
GCST011584_3	Metastatic colorectal cancer survival in treatment with chemotherapy plus biologics	5e-6
GCST009391_1480	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0004847	age at onset
EFO:0010457	Alpha ketoglutarate measurement
EFO:0010480	fumarate measurement
EFO:0010509	maleate measurement
EFO:0010456	allantoin measurement
EFO:0000714	survival time
EFO:1001480	metastatic colorectal cancer

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067366 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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
8.36	Kd	4.393	nM	CHEMBL3752910
8.36	ED50	4.393	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149514: Binding affinity to human STMN2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0044	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	10
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	4
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
uranyl acetate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
ascorbate-2-phosphate	decreases expression, affects binding, affects cotreatment	1
arsenite	increases methylation	1
sodium arsenite	increases expression, affects cotreatment	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
Chir 99021	increases expression, affects binding, decreases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
XAV939	affects binding, affects cotreatment, decreases expression	1
incobotulinumtoxinA	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Ascorbic Acid	decreases expression, affects binding, affects cotreatment	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydrocortisone	affects cotreatment, increases 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
CHEMBL5652556	Binding	Binding affinity to human STMN2 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for STMN2 across ~30M SureChEMBL compounds — explore on Sugi Predict.