SPINDOC

Summary

SPINDOC (spindlin interactor and repressor of chromatin binding, HGNC:25115) is a protein-coding gene on chromosome 11q13.1, encoding Spindlin interactor and repressor of chromatin-binding protein (Q9BUA3). Chromatin protein that stabilizes SPIN1 and enhances its association with histone H3 trimethylated at both ‘Lys-4’ and ‘Lys-9’ (H3K4me3K9me3).

Involved in DNA damage response and negative regulation of DNA-templated transcription. Is active in nucleus and site of DNA damage.

Source: NCBI Gene 144097 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_138471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25115
Approved symbol	SPINDOC
Name	spindlin interactor and repressor of chromatin binding
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SPIN-DOC
Ensembl gene	ENSG00000168005
Ensembl biotype	protein_coding
OMIM	621257
Entrez	144097

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000294244, ENST00000535820, ENST00000540893, ENST00000851079, ENST00000851080, ENST00000851081, ENST00000969021

RefSeq mRNA: 1 — MANE Select: NM_138471 NM_138471

CCDS: CCDS31594

Canonical transcript exons

ENST00000294244 — 6 exons

Exon	Start	End
ENSE00000909019	63818527	63818652
ENSE00001063927	63818216	63818365
ENSE00001219729	63818802	63819002
ENSE00001219748	63817805	63818134
ENSE00001219765	63813456	63813813
ENSE00004283661	63826928	63827716

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 91.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9571 / max 476.8643, expressed in 1770 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114829	8.9800	1707
114828	2.4451	1302
114830	2.0677	1203
114831	0.4643	227

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	91.22	gold quality
right testis	UBERON:0004534	90.84	gold quality
testis	UBERON:0000473	88.88	gold quality
ganglionic eminence	UBERON:0004023	88.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.79	gold quality
lower esophagus	UBERON:0013473	86.75	gold quality
ventricular zone	UBERON:0003053	86.71	gold quality
adenohypophysis	UBERON:0002196	86.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.47	gold quality
cerebellar hemisphere	UBERON:0002245	86.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.34	gold quality
body of uterus	UBERON:0009853	86.32	gold quality
cerebellar cortex	UBERON:0002129	86.29	gold quality
right coronary artery	UBERON:0001625	85.69	gold quality
anterior cingulate cortex	UBERON:0009835	85.55	gold quality
cortical plate	UBERON:0005343	85.39	gold quality
prefrontal cortex	UBERON:0000451	85.26	gold quality
cerebellum	UBERON:0002037	85.19	gold quality
hypothalamus	UBERON:0001898	85.16	gold quality
ascending aorta	UBERON:0001496	84.69	gold quality
thoracic aorta	UBERON:0001515	84.55	gold quality
right frontal lobe	UBERON:0002810	84.55	gold quality
pituitary gland	UBERON:0000007	84.51	gold quality
apex of heart	UBERON:0002098	84.50	gold quality
metanephros cortex	UBERON:0010533	84.10	gold quality
left uterine tube	UBERON:0001303	84.09	gold quality
stromal cell of endometrium	CL:0002255	84.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.90	gold quality
right atrium auricular region	UBERON:0006631	83.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting SPINDOC, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3065-5P	99.97	71.56	3281
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-6825-5P	99.96	69.81	3431
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031

Literature-anchored findings (GeneRIF, showing 4)

• identified SPIN.DOC as a transcriptional repressor that binds SPIN1 and masks its ability to engage the H3-Lys-4 trimethylation activation mark (PMID:29061846)
• SPINDOC Interacts with SPIN1 in DNA independent manner. SPINDOC regulates expression and chromatin loading of SPIN1. (PMID:30803761)
• SPINDOC binds PARP1 to facilitate PARylation. (PMID:34737271)
• Molecular Basis for SPINDOC-Spindlin1 Engagement and Its Role in Transcriptional Attenuation. (PMID:37977297)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spindoc	ENSMUSG00000024970
rattus_norvegicus	Spindoc	ENSRNOG00000025061

Protein

Protein identifiers

Spindlin interactor and repressor of chromatin-binding protein — Q9BUA3 (reviewed: Q9BUA3)

Alternative names: SPIN1-docking protein

All UniProt accessions (3): Q9BUA3, H0YGK9, H0YGY5

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin protein that stabilizes SPIN1 and enhances its association with histone H3 trimethylated at both ‘Lys-4’ and ‘Lys-9’ (H3K4me3K9me3). Positively regulates poly-ADP-ribosylation in response to DNA damage; acts by facilitating PARP1 ADP-ribosyltransferase activity.

Subunit / interactions. Interacts with SPIN1, SPIN2A, SPIN2B, SPIN3 and SPIN4. Interacts with TCF7L2 in a SPIN1-dependent manner. Interacts with PARP1; promoting PARP1 ADP-ribosyltransferase activity.

Subcellular location. Nucleus. Chromosome.

Induction. In response to DNA damage; expression is regulated by KLF4.

RefSeq proteins (1): NP_612480* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040647	SPIN-DOC_Znf-C2H2	Domain
IPR052675	ZnF_transloc-Spindlin_int	Family

Pfam: PF18658

UniProt features (22 total): modified residue 6, cross-link 6, region of interest 4, strand 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7CNA	X-RAY DIFFRACTION	1.6
7E9M	X-RAY DIFFRACTION	2.5
7EA1	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUA3-F1	51.71	0.10

Functional residue map

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

Post-translational modifications (12): 251, 308, 310, 48, 189, 220, 290, 294, 374, 121, 148, 248

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): ACTACCT_MIR196A_MIR196B, MAZ_Q6, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, AAAYRNCTG_UNKNOWN, chr11q13, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GTGCCTT_MIR506, MYOD_01, GOBP_DNA_DAMAGE_RESPONSE, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, NRF2_01, TGCCTTA_MIR124A, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B

GO Biological Process (4): DNA damage response (GO:0006974), regulation of protein ADP-ribosylation (GO:0010835), negative regulation of DNA-templated transcription (GO:0045892), DNA repair (GO:0006281)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), site of DNA damage (GO:0090734), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to stress	1
regulation of transferase activity	1
NAD+-protein mono-ADP-ribosyltransferase activity	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
DNA metabolic process	1
DNA damage response	1
binding	1
intracellular membrane-bounded organelle	1
chromosome	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINDOC	SPIN1	Q9Y657	666
SPINDOC	A6NDT3	A6NDT3	446
SPINDOC	SPIN2A	Q99865	446
SPINDOC	SPIN2B	Q9BPZ2	431
SPINDOC	TDRD5	Q8NAT2	418
SPINDOC	TEDC2	Q7L2K0	417
SPINDOC	SPIN3	Q5JUX0	412
SPINDOC	SPIN4	Q56A73	400
SPINDOC	SLC9D1	Q6UWJ1	370
SPINDOC	SAMD11	Q96NU1	349
SPINDOC	GCNA	Q96QF7	310
SPINDOC	THOC5	Q13769	263
SPINDOC	TOP3B	O95985	262
SPINDOC	DCAF6	Q58WW2	255
SPINDOC	DDX10	Q13206	251

IntAct

44 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
SPIN1	SPINDOC	psi-mi:“MI:0914”(association)	0.640
SPINDOC	SPIN3	psi-mi:“MI:0915”(physical association)	0.560
PIAS2	SPINDOC	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	SPINDOC	psi-mi:“MI:0915”(physical association)	0.560
SPINDOC	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
SPINDOC	SPIN3	psi-mi:“MI:0914”(association)	0.560
SPIN2B	WDHD1	psi-mi:“MI:0914”(association)	0.530
SPIN1	PAX3	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
ARRB2		psi-mi:“MI:0914”(association)	0.350
PARK7	SAP18	psi-mi:“MI:0914”(association)	0.350
CFAP20	PRPF40A	psi-mi:“MI:0914”(association)	0.350
SH3GL3	RBFOX3	psi-mi:“MI:0914”(association)	0.350
DOK2	ARPC2	psi-mi:“MI:0914”(association)	0.350
RIN1	H1-4	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
LOXL2	TUBB	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	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

BioGRID (65): C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS), C11orf84 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NEL2, A6NP61, B1ASB6, B1WBS3, B2RXF5, F6WEQ6, O15015, O43918, O88282, O88286, O95785, P98168, P98169, Q2M3G4, Q2MHN3, Q2QGD7, Q3U1J1, Q3U381, Q497V6, Q5SW24, Q5SXM2, Q6YND2, Q6ZMQ8, Q6ZMY3, Q7TN08, Q7TSX9, Q80SU3, Q80YE4, Q811H0, Q8BG26, Q8BZW2, Q8C8V1, Q8IX07, Q8IY92, Q8N143, Q8N1G0, Q8NC74, Q8TBE0

Diamond homologs: C9JLR9, Q05AH6, Q4VA45, Q9BUA3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
Clathrin-mediated endocytosis	5	12.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

843 predictions. Top by Δscore:

Variant	Effect	Δscore
11:63813811:GAG:G	donor_gain	1.0000
11:63813812:AGGT:A	donor_loss	1.0000
11:63813814:G:C	donor_loss	1.0000
11:63813815:T:G	donor_loss	1.0000
11:63817803:A:AC	acceptor_loss	1.0000
11:63817803:A:AG	acceptor_gain	1.0000
11:63817803:AGT:A	acceptor_gain	1.0000
11:63817804:G:GG	acceptor_gain	1.0000
11:63817804:G:GT	acceptor_loss	1.0000
11:63817804:GT:G	acceptor_gain	1.0000
11:63817804:GTG:G	acceptor_gain	1.0000
11:63818098:GAC:G	donor_gain	1.0000
11:63818108:C:G	donor_gain	1.0000
11:63818131:TCAG:T	donor_loss	1.0000
11:63818132:CAG:C	donor_loss	1.0000
11:63818134:GG:G	donor_loss	1.0000
11:63818135:GT:G	donor_loss	1.0000
11:63818136:T:A	donor_loss	1.0000
11:63818213:CAGAC:C	acceptor_loss	1.0000
11:63818214:A:AG	acceptor_gain	1.0000
11:63818214:A:AT	acceptor_loss	1.0000
11:63818215:G:GG	acceptor_gain	1.0000
11:63818215:GA:G	acceptor_gain	1.0000
11:63818215:GAC:G	acceptor_gain	1.0000
11:63818215:GACT:G	acceptor_gain	1.0000
11:63818215:GACTC:G	acceptor_gain	1.0000
11:63818363:CTG:C	donor_loss	1.0000
11:63818366:G:A	donor_loss	1.0000
11:63818367:T:G	donor_loss	1.0000
11:63818797:TCCA:T	acceptor_loss	1.0000

AlphaMissense

2469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:63817948:T:C	C91R	1.000
11:63817948:T:A	C91S	0.999
11:63817949:G:A	C91Y	0.999
11:63817949:G:C	C91S	0.999
11:63817950:C:G	C91W	0.999
11:63817957:T:C	C94R	0.999
11:63817958:G:A	C94Y	0.999
11:63817994:C:A	A106D	0.999
11:63818017:C:G	H114D	0.999
11:63818019:C:A	H114Q	0.999
11:63818019:C:G	H114Q	0.999
11:63818060:T:C	I128T	0.999
11:63818071:T:A	W132R	0.999
11:63818071:T:C	W132R	0.999
11:63818862:T:C	F265S	0.999
11:63818877:T:C	F270S	0.999
11:63818888:T:C	F274L	0.999
11:63818890:C:A	F274L	0.999
11:63818890:C:G	F274L	0.999
11:63817906:T:C	F77L	0.998
11:63817907:T:C	F77S	0.998
11:63817908:C:A	F77L	0.998
11:63817908:C:G	F77L	0.998
11:63817910:T:C	L78P	0.998
11:63817949:G:T	C91F	0.998
11:63817958:G:T	C94F	0.998
11:63817959:T:G	C94W	0.998
11:63818006:T:A	I110N	0.998
11:63818018:A:G	H114R	0.998
11:63818036:T:C	L120P	0.998

dbSNP variants (sampled 300 via entrez): RS1000102900 (11:63827008 C>G), RS1000217433 (11:63827557 A>G), RS1000257230 (11:63827605 G>T), RS1000331990 (11:63817035 G>A), RS1000514052 (11:63815358 G>C), RS1000730117 (11:63812275 G>A), RS1000761255 (11:63821452 C>G), RS1001174114 (11:63817662 G>T), RS1001839593 (11:63817453 G>A,C), RS1001900511 (11:63820658 G>A,C), RS1001966357 (11:63814271 C>G,T), RS1002016581 (11:63813134 G>A,T), RS1002076471 (11:63827061 C>T), RS1002336767 (11:63814529 G>T), RS1002870820 (11:63819413 G>A,C)

Disease associations

OMIM: gene MIM:621257 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001503_7	Electroencephalographic traits in alcoholism	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004800	frontal theta oscillation measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, decreases expression	2
FR900359	increases phosphorylation	1
sodium arsenate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
eprenetapopt	affects expression, affects reaction	1
licochalcone B	increases expression	1
PCI 5002	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Zinc	affects cotreatment, increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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