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): 13 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_007029

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: 4 — 4 protein_coding

ENST00000220876, ENST00000518111, ENST00000518491, ENST00000911966

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.

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

293 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

112 targeting STMN2, 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-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

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)

Protein

Protein identifiers

Stathmin-2 — Q93045 (reviewed: Q93045)

Alternative names: Superior cervical ganglion-10 protein

All UniProt accessions (2): Q93045, E5RGX5

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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 22, 24, 16, 50, 62, 73, 97

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9696273	RND1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
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 (12): 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), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
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

Protein interactions and networks

STRING

2814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STMN2	TRPC5	Q9UL62	808
STMN2	REST	Q13127	740
STMN2	GFAP	P14136	594
STMN2	JUN	P05412	577
STMN2	GAP43	P17677	576
STMN2	SYN1	P17600	548
STMN2	VPS26C	O14972	548
STMN2	NMNAT2	Q9BZQ4	542
STMN2	SCN2A	Q99250	523
STMN2	CRELD1	Q96HD1	500
STMN2	PSMG1	O95456	497
STMN2	KIF1B	O60333	493
STMN2	SOX2	P48431	489
STMN2	ACTL6B	O94805	486
STMN2	NRN1	Q9NPD7	479

IntAct

78 interactions, top by confidence:

A	B	Type	Score
TEX11	STMN2	psi-mi:“MI:0915”(physical association)	0.700
STMN2	TEX11	psi-mi:“MI:0915”(physical association)	0.700
STMN2	TXLNA	psi-mi:“MI:0915”(physical association)	0.670
SESTD1	STMN2	psi-mi:“MI:0915”(physical association)	0.670
CIB1	STMN2	psi-mi:“MI:0403”(colocalization)	0.660
CIB1	STMN2	psi-mi:“MI:0915”(physical association)	0.660
CIB1	STMN2	psi-mi:“MI:0407”(direct interaction)	0.660
STMN2	CIB1	psi-mi:“MI:0915”(physical association)	0.660
STMN2	CIB1	psi-mi:“MI:2364”(proximity)	0.660
CIB1	STMN2	psi-mi:“MI:2364”(proximity)	0.660
COMMD3	VPS26C	psi-mi:“MI:0914”(association)	0.640
STMN2	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
TFCP2	STMN2	psi-mi:“MI:0915”(physical association)	0.560
TEX11	STMN2	psi-mi:“MI:0915”(physical association)	0.560
CCHCR1	STMN2	psi-mi:“MI:0915”(physical association)	0.560
MBD3	STMN2	psi-mi:“MI:0915”(physical association)	0.560
PSMB1	STMN2	psi-mi:“MI:0915”(physical association)	0.560
STMN2	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
FAM90A1	STMN2	psi-mi:“MI:0915”(physical association)	0.560
STMN2	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
STMN2	MTA2	psi-mi:“MI:0914”(association)	0.530

BioGRID (101): STMN2 (Two-hybrid), TEX11 (Two-hybrid), TXLNA (Two-hybrid), STMN2 (Biochemical Activity), TEX11 (Two-hybrid), TEX11 (Affinity Capture-Western), FANCC (Two-hybrid), STMN2 (Two-hybrid), TEX11 (Two-hybrid), PSMC1 (Two-hybrid), STMN2 (Affinity Capture-MS), STMN2 (Affinity Capture-Western), STMN2 (Proximity Label-MS), STMN2 (Two-hybrid), STMN2 (Two-hybrid)

ESM2 similar proteins: A0A088MLT8, A2AQ19, A4FV29, A4IFK9, B3KU38, O14795, O70166, O93388, O95983, P21818, P31395, P50751, P54227, P55821, P63042, P63043, Q09001, Q09002, Q09004, Q09006, Q2KJ58, Q32L68, Q4KUS2, Q4R4N5, Q5F3L9, Q5FVJ5, Q5PSV4, Q5R4C5, Q5R562, Q5R8C6, Q5RAD5, Q62768, Q6GQB5, Q8IVM0, Q8IW50, Q8TBN0, Q8VDV3, Q90987, Q92541, Q93045

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

6 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703571	GRCh37/hg19 8q21.12-21.13(chr8:79982581-80674788)	Pathogenic

SpliceAI

887 predictions. Top by Δscore:

Variant	Effect	Δscore
8:79636800:A:AG	acceptor_gain	1.0000
8:79636801:G:GC	acceptor_gain	1.0000
8:79636801:GCC:G	acceptor_gain	1.0000
8:79636801:GCCTA:G	acceptor_gain	1.0000
8:79636894:GATG:G	donor_gain	1.0000
8:79636895:ATG:A	donor_gain	1.0000
8:79636895:ATGGT:A	donor_loss	1.0000
8:79636896:TG:T	donor_gain	1.0000
8:79636897:GG:G	donor_gain	1.0000
8:79636898:G:GG	donor_gain	1.0000
8:79636898:GTG:G	donor_loss	1.0000
8:79636899:T:A	donor_loss	1.0000
8:79636900:G:GT	donor_loss	1.0000
8:79641374:TCAGA:T	acceptor_loss	1.0000
8:79641375:CAG:C	acceptor_loss	1.0000
8:79641376:A:AG	acceptor_gain	1.0000
8:79641377:G:GA	acceptor_gain	1.0000
8:79641377:GAT:G	acceptor_gain	1.0000
8:79641377:GATAT:G	acceptor_gain	1.0000
8:79641540:A:T	donor_gain	1.0000
8:79641546:GAAAG:G	donor_gain	1.0000
8:79641549:AGGTA:A	donor_loss	1.0000
8:79641550:GGTA:G	donor_loss	1.0000
8:79641551:G:C	donor_loss	1.0000
8:79641551:G:GG	donor_gain	1.0000
8:79654869:A:AG	acceptor_gain	1.0000
8:79654870:G:GG	acceptor_gain	1.0000
8:79655012:G:GT	donor_gain	1.0000
8:79655013:A:T	donor_gain	1.0000
8:79636797:TTCA:T	acceptor_loss	0.9900

AlphaMissense

1177 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:79641422:T:C	F54L	1.000
8:79641424:T:A	F54L	1.000
8:79641424:T:G	F54L	1.000
8:79654986:T:C	L135P	1.000
8:79641414:G:A	G51D	0.999
8:79641423:T:C	F54S	0.999
8:79641525:T:C	L88P	0.999
8:79641533:G:C	A91P	0.999
8:79641543:G:C	R94T	0.999
8:79641544:A:C	R94S	0.999
8:79641544:A:T	R94S	0.999
8:79641546:G:C	R95T	0.999
8:79641547:A:C	R95S	0.999
8:79641547:A:T	R95S	0.999
8:79654961:T:C	F127L	0.999
8:79654963:C:A	F127L	0.999
8:79654963:C:G	F127L	0.999
8:79654973:G:C	A131P	0.999
8:79655019:G:C	R146P	0.999
8:79655052:T:C	L157P	0.999
8:79664837:G:C	R168P	0.999
8:79636846:T:C	C22R	0.998
8:79636852:T:C	C24R	0.998
8:79641413:G:C	G51R	0.998
8:79641414:G:T	G51V	0.998
8:79641435:T:C	L58S	0.998
8:79641530:G:C	A90P	0.998
8:79654890:T:C	L103P	0.998
8:79654901:G:C	A107P	0.998
8:79655018:C:A	R146S	0.998

dbSNP variants (sampled 300 via entrez): RS1000072842 (8:79634353 C>T), RS1000135187 (8:79627214 G>T), RS1000182352 (8:79628036 T>C), RS1000210618 (8:79617180 A>G), RS1000248447 (8:79641170 T>A,G), RS1000439503 (8:79640957 C>A,G,T), RS1000486060 (8:79627648 T>C), RS1000517189 (8:79613271 A>C), RS1000541573 (8:79652739 C>A), RS1000608441 (8:79654272 C>A), RS1000619484 (8:79646081 T>G), RS1000624614 (8:79627694 CATAT>C,CATATAT), RS1000671628 (8:79645777 T>C), RS1000805968 (8:79620449 A>G), RS1000833924 (8:79616390 C>T)

Disease associations

OMIM: gene MIM:600621 | disease phenotypes: MIM:150230

GenCC curated gene-disease

Mondo (1): trichorhinophalangeal syndrome type II (MONDO:0007874)

Orphanet (1): Trichorhinophalangeal syndrome type 2 (Orphanet:502)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000294_1	Creutzfeldt-Jakob disease	6.000000e-08
GCST002868_12	Response to serotonin reuptake inhibitors in major depressive disorder	9.000000e-07
GCST006149_4	Frontotemporal dementia with GRN mutation (age at onset)	4.000000e-06
GCST009391_1130	Metabolite levels	8.000000e-06
GCST009391_1776	Metabolite levels	9.000000e-07
GCST011584_3	Metastatic colorectal cancer survival in treatment with chemotherapy plus biologics	5.000000e-06

EFO canonical traits (8, from GWAS)

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

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015826	Langer-Giedion Syndrome	C05.116.099.708.582

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067366 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs113889867	STMN2		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
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 cotreatment, increases expression, affects 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	affects cotreatment, increases expression	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	affects cotreatment, increases expression, affects binding, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression, affects cotreatment	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	affects cotreatment, decreases expression, affects binding	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)

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