SPIN3

Summary

SPIN3 (spindlin family member 3, HGNC:27272) is a protein-coding gene on chromosome Xp11.21, encoding Spindlin-3 (Q5JUX0). Exhibits H3K4me3-binding activity.

Enables methylated histone binding activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in membrane. Predicted to be active in cytosol and nucleoplasm.

Source: NCBI Gene 169981 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 52 total
• Druggable target: yes
• MANE Select transcript: NM_001010862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27272
Approved symbol	SPIN3
Name	spindlin family member 3
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	TDRD27
Ensembl gene	ENSG00000204271
Ensembl biotype	protein_coding
Entrez	169981

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 33 nonsense_mediated_decay, 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000374919, ENST00000475785, ENST00000478405, ENST00000638257, ENST00000638289, ENST00000638341, ENST00000638386, ENST00000638481, ENST00000638619, ENST00000638664, ENST00000638712, ENST00000638819, ENST00000638834, ENST00000638845, ENST00000638873, ENST00000638940, ENST00000639000, ENST00000639007, ENST00000639053, ENST00000639257, ENST00000639418, ENST00000639482, ENST00000639525, ENST00000639583, ENST00000639605, ENST00000639607, ENST00000639791, ENST00000639794, ENST00000639809, ENST00000639888, ENST00000639895, ENST00000639956, ENST00000640039, ENST00000640101, ENST00000640104, ENST00000640131, ENST00000640187, ENST00000640421, ENST00000640463, ENST00000640507, ENST00000640511, ENST00000640577, ENST00000640717, ENST00000640728, ENST00000640768

RefSeq mRNA: 1 — MANE Select: NM_001010862 NM_001010862

CCDS: CCDS43963

Canonical transcript exons

ENST00000374919 — 2 exons

Exon	Start	End
ENSE00001932860	56990831	56994949
ENSE00003805021	56995216	56995541

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 96.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5948 / max 79.8529, expressed in 1544 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199425	5.0024	1530
199424	0.5924	287

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.21	gold quality
oocyte	CL:0000023	92.17	gold quality
cerebellar hemisphere	UBERON:0002245	89.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.95	gold quality
cerebellar cortex	UBERON:0002129	88.92	gold quality
cortical plate	UBERON:0005343	88.26	gold quality
cerebellum	UBERON:0002037	87.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.32	gold quality
ganglionic eminence	UBERON:0004023	83.54	gold quality
adenohypophysis	UBERON:0002196	83.41	gold quality
right frontal lobe	UBERON:0002810	83.34	gold quality
anterior cingulate cortex	UBERON:0009835	83.07	gold quality
hypothalamus	UBERON:0001898	82.93	gold quality
prefrontal cortex	UBERON:0000451	82.92	gold quality
tibial nerve	UBERON:0001323	82.90	gold quality
right ovary	UBERON:0002118	82.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.80	gold quality
nucleus accumbens	UBERON:0001882	82.53	gold quality
caudate nucleus	UBERON:0001873	82.45	gold quality
left ovary	UBERON:0002119	82.30	gold quality
pituitary gland	UBERON:0000007	82.25	gold quality
right lobe of liver	UBERON:0001114	82.04	gold quality
endocervix	UBERON:0000458	81.99	gold quality
body of pancreas	UBERON:0001150	81.93	gold quality
putamen	UBERON:0001874	81.77	gold quality
neocortex	UBERON:0001950	81.77	gold quality
frontal cortex	UBERON:0001870	81.65	gold quality
calcaneal tendon	UBERON:0003701	81.59	gold quality
body of uterus	UBERON:0009853	81.54	gold quality
endothelial cell	CL:0000115	81.53	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting SPIN3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	spinb	ENSDARG00000035697
danio_rerio	spina	ENSDARG00000058949

Paralogs (4): SPIN1 (ENSG00000106723), SPIN2A (ENSG00000147059), SPIN4 (ENSG00000186767), SPIN2B (ENSG00000186787)

Protein

Protein identifiers

Spindlin-3 — Q5JUX0 (reviewed: Q5JUX0)

Alternative names: Spindlin-like protein 3

All UniProt accessions (6): A0A1W2PPF7, A0A1W2PPL1, A0A1W2PQU8, A0A1W2PR54, A0A1W2PRP6, Q5JUX0

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits H3K4me3-binding activity.

Subunit / interactions. Interacts with C11orf84/SPINDOC.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the SPIN/STSY family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JUX0-1	1	yes
Q5JUX0-2	2

RefSeq proteins (1): NP_001010862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003671	SPIN/Ssty	Family
IPR042567	SPIN/Ssty_sf	Homologous_superfamily

Pfam: PF02513

UniProt features (31 total): strand 15, region of interest 6, site 3, splice variant 2, helix 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5A1H	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JUX0-F1	81.63	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 169 (histone h3k4me3 and h3r8me2a binding); 176 (histone h3k4me3 and h3r8me2a binding); 180 (histone h3k4me3 and h3r8me2a binding)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 50 (showing top): FISCHER_G1_S_CELL_CYCLE, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, ZHAN_MULTIPLE_MYELOMA_MS_DN, WHITFIELD_CELL_CYCLE_G1_S, chrXp11, PEDRIOLI_MIR31_TARGETS_DN, ZWANG_DOWN_BY_2ND_EGF_PULSE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR548E_5P, MIR10527_5P, MIR182_5P, MIR4306, MIR6875_3P, MIR5010_3P, MIR577

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), gamete generation (GO:0007276), chromatin organization (GO:0006325)

GO Molecular Function (2): histone H3K4me3 reader activity (GO:0140002), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
sexual reproduction	1
multicellular organismal reproductive process	1
cellular component organization	1
histone H3 reader activity	1
binding	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPIN3	FAM228A	Q86W67	447
SPIN3	SPINDOC	Q9BUA3	412
SPIN3	PAX3	P23760	373
SPIN3	DUXB	A0A1W2PPF3	370
SPIN3	PLS3	P13797	367
SPIN3	SPNS1	Q9H2V7	355
SPIN3	FOXA3	P55318	353
SPIN3	SETDB1	Q15047	349
SPIN3	KAT7	O95251	348
SPIN3	GRIPAP1	Q4V328	336
SPIN3	ZGRF1	Q86YA3	336
SPIN3	C9JR48	C9JR48	317
SPIN3	DPRX	A6NFQ7	317
SPIN3	SLC25A47	Q6Q0C1	310
SPIN3	PUM1	Q14671	305
SPIN3	ZNF101	Q8IZC7	305

IntAct

32 interactions, top by confidence:

A	B	Type	Score
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
NUDT1	ACY1	psi-mi:“MI:0914”(association)	0.670
SPINDOC	SPIN3	psi-mi:“MI:0915”(physical association)	0.560
SPINDOC	SPIN3	psi-mi:“MI:0914”(association)	0.560
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
NOL9	IPO5	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF324	psi-mi:“MI:0914”(association)	0.530
SPIN3	VIM	psi-mi:“MI:0915”(physical association)	0.400
SPIN3	NDOR1	psi-mi:“MI:0915”(physical association)	0.400
SERBP1	SPIN3	psi-mi:“MI:0915”(physical association)	0.400
ARRB2		psi-mi:“MI:0914”(association)	0.350
ARHGEF40	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	ELP1	psi-mi:“MI:0914”(association)	0.350
DAXX	HAT1	psi-mi:“MI:0914”(association)	0.350
PRDM7	SNRPD2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
DEFB107A	ZZEF1	psi-mi:“MI:0914”(association)	0.350
SPINDOC	TRAF3IP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Proximity Label-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), ATXN7L1 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS)

ESM2 similar proteins: A2Z4C5, A7X680, B8AJL9, F4HVW5, F4I933, F4IV66, F4JR57, K4DF01, P0C7Q8, P13675, Q0WPN7, Q10PL5, Q1ECE0, Q2KI39, Q33BI9, Q4V8J7, Q56A73, Q5JUX0, Q5R997, Q5RA80, Q5RAW7, Q61142, Q6NVE3, Q6YZM6, Q8GVE5, Q8K1L2, Q8L7G0, Q8LJW3, Q8RWD9, Q8RWY4, Q8RY82, Q8W4F0, Q90WG1, Q90WG2, Q93VH2, Q93XX4, Q93YR9, Q944S3, Q94BM7, Q99865

Diamond homologs: P13675, Q2KI39, Q4V8J7, Q56A73, Q5JUX0, Q5R997, Q5RA80, Q5RAW7, Q61142, Q6NVE3, Q8K1L2, Q90WG1, Q90WG2, Q99865, Q9BPZ2, Q9Y657

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

299 predictions. Top by Δscore:

Variant	Effect	Δscore
X:56994981:C:CT	acceptor_gain	0.9900
X:56994982:G:T	acceptor_gain	0.9900
X:56995284:G:A	donor_gain	0.9900
X:56995293:T:TA	donor_gain	0.9900
X:56995429:C:A	donor_gain	0.9900
X:56995290:G:A	donor_gain	0.9800
X:56995428:T:TA	donor_gain	0.9800
X:56995460:T:TA	donor_gain	0.9800
X:56995205:T:TA	donor_gain	0.9700
X:56995215:C:A	donor_gain	0.9500
X:56994972:C:CT	acceptor_gain	0.9400
X:56995245:C:A	donor_gain	0.9400
X:56995413:A:AC	donor_gain	0.9400
X:56995244:T:TA	donor_gain	0.9300
X:56995367:T:TA	donor_gain	0.9300
X:56995415:G:T	donor_gain	0.9300
X:56995434:G:A	donor_gain	0.9300
X:56995346:G:A	donor_gain	0.9200
X:56994973:A:T	acceptor_gain	0.9100
X:56995257:G:A	donor_gain	0.9000
X:56995513:C:CA	donor_gain	0.8900
X:56995129:T:A	donor_gain	0.8800
X:56995414:TG:T	donor_gain	0.8700
X:56995450:T:TA	donor_gain	0.8600
X:56995443:T:TA	donor_gain	0.8500
X:56995282:T:TA	donor_gain	0.8200
X:56995198:C:CA	donor_gain	0.8100
X:56994949:CCTG:C	acceptor_loss	0.8000
X:56994950:CT:C	acceptor_loss	0.8000
X:56994951:T:G	acceptor_loss	0.8000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000300463 (X:56995734 G>A), RS1000439349 (X:56995455 C>T), RS1000493287 (X:56984278 T>C), RS1000511315 (X:56982090 G>A,C), RS1000703515 (X:56975291 G>A), RS1000790534 (X:56995106 T>A,C), RS1000808765 (X:56995466 T>TGGCGGC), RS1001051465 (X:56974956 C>T), RS1001266897 (X:56979446 G>A), RS1001317362 (X:56979952 T>C), RS1001616711 (X:56989206 G>A), RS1001628775 (X:56986119 G>A), RS1001857423 (X:56974795 T>G), RS1002054275 (X:56997055 C>T), RS1002075280 (X:56982699 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006661_145	Male-pattern baldness	6.000000e-19
GCST006979_841	Heel bone mineral density	8.000000e-24
GCST009799_6	Alcohol consumption (drinkers vs non-drinkers)	2.000000e-08
GCST90002395_636	Mean platelet volume	2.000000e-152

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004329	alcohol drinking

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523325 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.88	Kd	131.1	nM	CHEMBL4451634
6.77	Kd	170	nM	CHEMBL4552020
5.85	Kd	1400	nM	CHEMBL5594627

PubChem BioAssay actives

3 with measured affinity, of 5 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[4-[2-[[2-[3-[2-amino-5-(cyclopropylmethoxy)-3,3-dimethylindol-6-yl]oxypropyl]-1,3-dihydroisoindol-5-yl]oxy]ethyl]triazol-1-yl]-1-[4-(2-pyrrolidin-1-ylethyl)piperidin-1-yl]ethanone	1526488: Binding affinity to recombinant human His-tagged SPIN3 (27 to 258 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	0.1311	uM
[3-(aminomethyl)-5-[3-(1,3-dihydroisoindol-2-yl)propoxy]-4-methoxyphenyl]methanamine	1578936: Inhibition of recombinant human N-terminal His6-tagged SPIN3 (27 to 258 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by isothermal titration calorimetry	kd	0.1700	uM
N-[7-[3-(1,3-dihydroisoindol-2-yl)propoxy]-6-methoxy-4-pyrrolidin-1-ylquinazolin-2-yl]-N’,N’-dimethylethane-1,2-diamine	2103452: Binding affinity to human N-terminal His6 tagged SPIN3 (M27 to S258 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	1.4000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	6
Benzo(a)pyrene	affects methylation, decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects expression, affects reaction	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4323088	Binding	Binding affinity to recombinant human His-tagged SPIN3 (27 to 258 residues) expressed in Escherichia coli BL21 (DE3) assessed as melting temperature at 20 uM by Sypro orange dye based differential scanning fluorimetry	A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function. — J Med Chem

Clinical trials (associated diseases)

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