RSF1

Summary

RSF1 (remodeling and spacing factor 1, HGNC:18118) is a protein-coding gene on chromosome 11q14.1, encoding Remodeling and spacing factor 1 (Q96T23). Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. In precision oncology, RSF1 Amplification is associated with resistance to Tamoxifen in Breast Cancer (CIViC Level B).

This gene encodes a nuclear protein that interacts with hepatitis B virus X protein (HBX) and facilitates transcription of hepatitis B virus genes by the HBX transcription activator, suggesting a role for this interaction in the virus life cycle. This protein also interacts with SNF2H protein to form the RSF chromatin-remodeling complex, where the SNF2H subunit functions as the nucleosome-dependent ATPase, and this protein as the histone chaperone.

Source: NCBI Gene 51773 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 202 total
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_016578

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18118
Approved symbol	RSF1
Name	remodeling and spacing factor 1
Location	11q14.1
Locus type	gene with protein product
Status	Approved
Aliases	XAP8, RSF-1, p325
Ensembl gene	ENSG00000048649
Ensembl biotype	protein_coding
OMIM	608522
Entrez	51773

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000308488, ENST00000440064, ENST00000467567, ENST00000480887, ENST00000526324, ENST00000528095, ENST00000529470, ENST00000530604, ENST00000531026, ENST00000531768, ENST00000532556, ENST00000534794

RefSeq mRNA: 1 — MANE Select: NM_016578 NM_016578

CCDS: CCDS8253

Canonical transcript exons

ENST00000308488 — 16 exons

Exon	Start	End
ENSE00001040461	77691159	77691238
ENSE00001040464	77725545	77725699
ENSE00001040477	77676792	77676999
ENSE00001040478	77685105	77685159
ENSE00001040482	77672042	77672230
ENSE00001040487	77675036	77675256
ENSE00001040489	77678086	77678153
ENSE00001040492	77683710	77683819
ENSE00001153197	77764598	77764689
ENSE00001182767	77700721	77702495
ENSE00001826540	77660009	77667491
ENSE00002199384	77820528	77820722
ENSE00003477981	77747036	77747128
ENSE00003521990	77740731	77740936
ENSE00003558465	77698487	77698693
ENSE00003652732	77693507	77693611

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8706 / max 588.4982, expressed in 1810 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121448	23.2944	1806
121451	1.1666	693
121450	0.8842	477
206396	0.4771	277
121449	0.4467	212
206395	0.3817	189
206394	0.2199	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.58	gold quality
tendon	UBERON:0000043	97.47	gold quality
medial globus pallidus	UBERON:0002477	97.47	gold quality
sural nerve	UBERON:0015488	97.27	gold quality
globus pallidus	UBERON:0001875	97.00	gold quality
colonic epithelium	UBERON:0000397	96.48	gold quality
tendon of biceps brachii	UBERON:0008188	96.32	gold quality
cerebellar vermis	UBERON:0004720	95.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.74	gold quality
middle temporal gyrus	UBERON:0002771	95.72	gold quality
lateral globus pallidus	UBERON:0002476	95.71	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.42	gold quality
inferior vagus X ganglion	UBERON:0005363	95.20	gold quality
corpus callosum	UBERON:0002336	95.19	gold quality
buccal mucosa cell	CL:0002336	95.08	silver quality
entorhinal cortex	UBERON:0002728	95.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.85	gold quality
substantia nigra pars compacta	UBERON:0001965	94.80	gold quality
cardia of stomach	UBERON:0001162	94.69	gold quality
ventral tegmental area	UBERON:0002691	94.65	gold quality
pylorus	UBERON:0001166	94.56	gold quality
adrenal tissue	UBERON:0018303	94.39	gold quality
ventricular zone	UBERON:0003053	94.20	gold quality
renal medulla	UBERON:0000362	94.04	gold quality
sperm	CL:0000019	93.89	gold quality
superficial temporal artery	UBERON:0001614	93.87	gold quality
cortical plate	UBERON:0005343	93.78	gold quality
ganglionic eminence	UBERON:0004023	93.76	gold quality
endothelial cell	CL:0000115	93.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AIP, NFKB

miRNA regulators (miRDB)

131 targeting RSF1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
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-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6835-3P	99.93	70.49	2904

Literature-anchored findings (GeneRIF, showing 40)

• HBXAP represses NF-kappaB-mediated gene activation in a dose-dependent manner. Our results showed that HBXAP and NF-kappaB colocalize to the nuclear matrix with specific physical interaction between them. (PMID:15242768)
• An important role of Rsf-1 amplification in ovarian cancer was shown. (PMID:16172393)
• Putative oncogene in ovarian cancer. (PMID:16418735)
• Rsf-1 expression is down-regulated in breast carcinoma cells in effusions compared with the solid counterparts and has no prognostic role at this anatomic site. (PMID:18289639)
• In an ovarian carcinoma cohort, RSF1 was amplified in 12% of the cases. It was correlated with serous histology and a worse prognosis. The 11q13 amplicon in ovarian cancer is likely driven by a cassette of genes rather than by a single oncogene. (PMID:18314909)
• findings suggest that interaction between Rsf-1 and hSNF2H may define a survival signal in those tumors overexpressing Rsf-1 (PMID:18519663)
• Rsf-1 is the major gene within the 11q13.5 amplicon that contributes to paclitaxel resistance in ovarian cancers. (PMID:19190325)
• continued expression of the ATX transgenes can contribute to hepatocyte transformation but are not sufficient to trigger neoplastic changes in the liver (PMID:19475691)
• Suggest that overexpression of Rsf-1, cyclin E and FASN occurs early in ovarian tumor progression. (PMID:20228782)
• Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability (PMID:20923775)
• a higher expression level of Rsf-1 is associated with advanced clinical stage and lymph node metastasis in ovarian clear-cell carcinoma. (PMID:21131837)
• our results suggest that RSF-1 up-regulation is associated with several clinicopathological features of disease aggressiveness in oral squamous cell carcinoma (PMID:21514451)
• Rsf-1 overexpression is common and associated with adverse prognosticators in gallbladder carcinomas. (PMID:21995635)
• Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response in nasopharyngeal carcinoma. (PMID:22081787)
• Rsf-1 is overexpressed in non-small cell lung cancers and contributes to malignant cell growth by cyclin D1 and ERK modulation. (PMID:22387541)
• Rsf-1 is overexpressed in colon cancers and contributes to malignant cell growth by cyclin E and phospho-Rb modulation, which makes Rsf-1 a candidate therapeutic target in colon cancer. (PMID:22528946)
• High-expression of Rsf-1 is associated with poor therapeutic response and adverse outcome in rectal cancer patients treated with neoadjuvant chemoradiotherapy. (PMID:22569540)
• Overexpression of Rsf-1 is associated with higher tumour stage and poorer clinical outcome in urinary bladder urothelial carcinoma. (PMID:22685262)
• High RSF-1 expression correlates with poor prognosis in patients with gastric adenocarcinoma. (PMID:22977663)
• Rsf-1 interacts and collaborates with cyclin E1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour-promoting functions of the RSF/cyclin E1 complex. (PMID:23378270)
• Serum HBXAP DNA from 65 lung cancer patients and 20 healthy controls was quantified using real-time fluorescent quantitative polymerase chain reaction. (PMID:23456648)
• Rsf-1 increases the frequency of abnormal mitotic events by disrupting hBubR1-Cdc20 interactions. (PMID:23536579)
• Remodeling and spacing factor 1 promotes the assembly of CENP-S and CENP-X at damaged chromatin and regulates DSB repair by homologous recombination and non-homologous end-joining. (PMID:23974106)
• Chromatin remodeler Rsf-1 is a guard in DNA damage checkpoints and homologous recombination repair. (PMID:24351651)
• Rsf-1 contributes to prostate cancer cell growth and invasion, which makes it a candidate therapeutic target. (PMID:24584698)
• Rsf-1 contributes to hepatocellular carcinoma cell growth through regulation of cell cycle proteins. (PMID:24798976)
• RSF1 facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins. (PMID:24800743)
• RSF1 plays a critical role in DNA double stranded break repair, a process in which it acts independently from its binding partner SMARCA5. (PMID:25111480)
• High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling. (PMID:25337201)
• essential centromeric component that recruits PLK1 to kinetochores and plays a crucial role in faithful cell division (PMID:26259146)
• Rsf-1 was overexpressed in lung cancer and associated with poor survival. Rsf-1 regulated cell invasion through MMP2 and NF-kappaB pathway. (PMID:28289901)
• In osteosarcoma patients, RSF1 was increased and associated with advanced clinical features and poor overall survival. (PMID:28843909)
• these data identify RSF1 as a H2Aub reader that contributes to H2Aub-mediated gene silencing by maintaining a stable nucleosome pattern at promoter regions. (PMID:28855339)
• Results show that RSF1 is highly expressed in bladder cancer tissues (BC) and is negatively correlated with miR-154 levels. RSF1 is a direct target by miR-154 in BC cells. There was however no significant effect on RSF1 mRNA levels, which may be due to incomplete complementation with the 3’-UTR. (PMID:29048677)
• Rsf-1 was highly expressed in H460 and H1299 cells. Rsf-1 knockout caused cell arrest at the G1 phase, increased cell apoptosis, and decreased migration and cell proliferation. Rsf-1 knockout increased the inhibition of cell proliferation, the reduction in cell migration and the augment in cell apoptosis in paclitaxel treated H460 and H1299 cells. (PMID:29258089)
• Remodeling and spacing factor 1 (RSF1) stability is regulated at the post-translational level upon DNA damage. (PMID:29385673)
• regulates the dynamics of H2A histone modifications at mitotic centromeres and contributes to the maintenance of chromosome stability (PMID:30242288)
• RSF1 is necessary for p53-dependent gene expression. (PMID:30348983)
• Rsf1 positively regulated Bcell lymphoma 2 (Bcl2), cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2, and downregulated Bcl2associated X protein expression. Nuclear factor kappalightchainenhancer of activated Bcells (NFkappaB) inhibition reversed the effects of Rsf1 on Bcl2. (PMID:31485613)
• Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR-146a-5p. (PMID:31960423)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rsf1b.1	ENSDARG00000068640
danio_rerio	rsf1b.1	ENSDARG00000093503
mus_musculus	Rsf1	ENSMUSG00000035623
rattus_norvegicus	Rsf1	ENSRNOG00000024194
drosophila_melanogaster	tth	FBGN0030502
drosophila_melanogaster	d4	FBGN0033015
caenorhabditis_elegans		WBGENE00016200

Paralogs (9): DPF1 (ENSG00000011332), KAT6A (ENSG00000083168), KAT8 (ENSG00000103510), PHF10 (ENSG00000130024), DPF2 (ENSG00000133884), KAT7 (ENSG00000136504), KAT6B (ENSG00000156650), KAT5 (ENSG00000172977), DPF3 (ENSG00000205683)

Protein

Protein identifiers

Remodeling and spacing factor 1 — Q96T23 (reviewed: Q96T23)

Alternative names: HBV pX-associated protein 8, Hepatitis B virus X-associated protein, p325 subunit of RSF chromatin-remodeling complex

All UniProt accessions (6): Q96T23, H0YCN2, H0YDG9, H0YER1, H0YEX0, H7C306

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex. Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively. The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex. The complexes do not have the ability to slide mononucleosomes to the center of a DNA template. Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain.

Subunit / interactions. Component of the RSF-1 ISWI chromatin-remodeling complex at least composed of SMARCA1 and RSF1. Within the RSF-1 ISWI chromatin-remodeling complex interacts with SMARCA1. Component of the RSF-5 ISWI chromatin-remodeling complex (also called the RSF complex) at least composed of SMARCA5/SNF2H and RSF1. Within the RSF-5 ISWI chromatin-remodeling complex interacts with SMARCA5/SNF2H; the interaction is direct. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Also binds the HBV pX/HBx protein, which is required to activate transcription of the viral genome.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed. Highly expressed in the heart, skeletal muscle, kidney and placenta. Expressed at low levels in the brain and colon.

Post-translational modifications. Phosphorylated.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96T23-1	1, Alpha, XAP8alpha	yes
Q96T23-2	2, Beta
Q96T23-3	3, Gamma

RefSeq proteins (1): NP_057662* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR028938	Rsf1-like	Family
IPR028942	WHIM1_dom	Domain

Pfam: PF00628, PF15612

UniProt features (125 total): cross-link 45, modified residue 30, compositionally biased region 25, sequence conflict 11, region of interest 6, splice variant 2, sequence variant 2, chain 1, domain 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96T23-F1	48.31	0.11

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 (75): 663, 670, 677, 698, 709, 758, 768, 795, 799, 1039, 227, 392, 397, 429, 473, 524, 570, 604, 622, 628 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-1640170	Cell Cycle
R-HSA-73886	Chromosome Maintenance
R-HSA-774815	Nucleosome assembly

MSigDB gene sets: 211 (showing top): RNGTGGGC_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TATTATA_MIR374, CACCAGC_MIR138, NFKB_Q6, SRF_Q5_01, NFKB_C, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, CDP_01, SRF_C, SMID_BREAST_CANCER_LUMINAL_B_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_256, IRF1_Q6, GATA1_01

GO Biological Process (9): chromatin organization (GO:0006325), nucleosome assembly (GO:0006334), chromatin remodeling (GO:0006338), DNA-templated transcription initiation (GO:0006352), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA binding (GO:0043392), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of viral transcription (GO:0050434)

GO Molecular Function (5): zinc ion binding (GO:0008270), histone binding (GO:0042393), histone octamer slider activity (GO:0140751), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), RSF complex (GO:0031213), chromatin (GO:0000785)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nucleosome assembly	1
Cell Cycle	1
Chromosome Maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	4
chromatin organization	2
regulation of DNA-templated transcription	2
cellular anatomical structure	2
cellular component organization	1
nucleosome organization	1
protein-DNA complex assembly	1
RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
DNA binding	1
negative regulation of binding	1
regulation of DNA binding	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
viral transcription	1
regulation of viral transcription	1
positive regulation of viral process	1
transition metal ion binding	1
protein binding	1
ATP-dependent chromatin remodeler activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
ISWI-type complex	1
chromosome	1

Protein interactions and networks

STRING

1813 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSF1	HSP90AA1	P07900	981
RSF1	HSP90AB1	P08238	981
RSF1	SMARCA5	O60264	975
RSF1	CHRAC1	Q9NRG0	763
RSF1	BAZ1B	Q9UIG0	759
RSF1	SMARCA1	P28370	709
RSF1	SUPT6H	Q7KZ85	683
RSF1	SRC	P12931	679
RSF1	POLE3	Q9NRF9	678
RSF1	BAZ1A	Q9NRL2	673
RSF1	SUPT5H	O00267	597
RSF1	AIP	O00170	595
RSF1	SMARCC1	Q92922	581
RSF1	CCNE1	P24864	578
RSF1	TP53	P04637	567

IntAct

83 interactions, top by confidence:

A	B	Type	Score
SMARCA1	RBBP4	psi-mi:“MI:0914”(association)	0.770
HMGB1	RSF1	psi-mi:“MI:0915”(physical association)	0.670
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
SMARCA5	RSF1	psi-mi:“MI:0915”(physical association)	0.670
SMARCA5	RSF1	psi-mi:“MI:0403”(colocalization)	0.670
RSF1	SMARCA5	psi-mi:“MI:0407”(direct interaction)	0.670
RSF1	SMARCA5	psi-mi:“MI:0915”(physical association)	0.670
SMARCA5	RBBP4	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RSF1	E2	psi-mi:“MI:0915”(physical association)	0.490
Dlg4	RSF1	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
	RSF1	psi-mi:“MI:0915”(physical association)	0.400
RSF1	HK1	psi-mi:“MI:0915”(physical association)	0.400
Tpx2	NFKBIE	psi-mi:“MI:0914”(association)	0.350
Kif20a	TNRC18	psi-mi:“MI:0914”(association)	0.350
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
MARK2	WDR46	psi-mi:“MI:0914”(association)	0.350
Cbx1		psi-mi:“MI:0914”(association)	0.350
Chaf1a	CBX5	psi-mi:“MI:0914”(association)	0.350
Psmd6	MIF4GD	psi-mi:“MI:0914”(association)	0.350
KAT6A	ING5	psi-mi:“MI:0914”(association)	0.350
ATXN3	HLA-A	psi-mi:“MI:0914”(association)	0.350
Fbxo21	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
HMGB1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (186): RSF1 (Proximity Label-MS), RSF1 (Proximity Label-MS), RSF1 (Proximity Label-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), RSF1 (Affinity Capture-Western)

ESM2 similar proteins: A6H5Y1, A8MW92, B7ZS37, E1BLP6, E7F888, O60284, P0C2N5, P46100, P59598, Q0P5X5, Q13029, Q14865, Q3U285, Q3U8K7, Q4V9H5, Q568E2, Q5BJ10, Q5EXX3, Q5F3G6, Q5RD97, Q5REF4, Q5ZJ69, Q5ZJK5, Q61687, Q63755, Q68FE9, Q6KAQ7, Q6P9P0, Q6ZV73, Q7YQM3, Q7YQM4, Q8BLG0, Q8BM75, Q8BRH4, Q8BZ32, Q8CCJ9, Q8IX21, Q8IXJ9, Q8IYH5, Q8K2Y0

Diamond homologs: A0A1W2PPD8, A1A5Q5, A1YVX4, A2A8L1, A2AUY4, A2BIL7, A6H619, A8DZJ1, A9LMC0, B2RXH2, B7ZS37, B9RU15, C0SUT9, D3ZD32, F4I240, F4I6G4, F4KIX0, O16102, O43918, O64752, O75164, O88379, O94953, O97159, P29375, P39956, P41228, P41229, P41230, P56163, P58268, P58269, P58270, Q03833, Q09477, Q10RP4, Q12873, Q14839, Q22516, Q23541

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PLK1	“up-regulates activity”	RSF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
Deposition of new CENPA-containing nucleosomes at the centromere	7	17.9×	4e-05
ChAHP complex assembly	6	17.8×	1e-04
FXIIa activates plasma kallikrein-kinin system	6	16.7×	1e-04
SIRT1 negatively regulates rRNA expression	6	16.5×	1e-04
Defective pyroptosis	6	15.1×	1e-04
RNA Polymerase I Promoter Opening	5	14.8×	5e-04
PRC2 methylates histones and DNA	6	14.7×	1e-04
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	6	14.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	9	30.6×	9e-09
nucleosome assembly	10	18.7×	4e-08
chromatin organization	8	10.6×	2e-04
chromatin remodeling	7	6.8×	7e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	177
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3416 predictions. Top by Δscore:

Variant	Effect	Δscore
11:77672227:CTTT:C	acceptor_gain	1.0000
11:77672236:T:TC	acceptor_gain	1.0000
11:77675065:T:TA	donor_gain	1.0000
11:77675263:A:T	acceptor_gain	1.0000
11:77676791:C:CA	donor_gain	1.0000
11:77676813:T:TA	donor_gain	1.0000
11:77676997:CTC:C	acceptor_gain	1.0000
11:77676999:CCTGA:C	acceptor_loss	1.0000
11:77677000:C:CC	acceptor_gain	1.0000
11:77677000:C:CG	acceptor_loss	1.0000
11:77677001:T:G	acceptor_loss	1.0000
11:77677005:T:TC	acceptor_gain	1.0000
11:77677006:T:C	acceptor_gain	1.0000
11:77677006:T:TC	acceptor_gain	1.0000
11:77677022:C:CT	acceptor_gain	1.0000
11:77677023:G:T	acceptor_gain	1.0000
11:77678081:CATA:C	donor_loss	1.0000
11:77678082:ATACC:A	donor_loss	1.0000
11:77678083:TA:T	donor_loss	1.0000
11:77678084:A:AC	donor_gain	1.0000
11:77678084:A:C	donor_loss	1.0000
11:77678084:ACCT:A	donor_gain	1.0000
11:77678085:C:A	donor_loss	1.0000
11:77678085:C:CC	donor_gain	1.0000
11:77678085:CCT:C	donor_gain	1.0000
11:77678085:CCTC:C	donor_gain	1.0000
11:77678087:T:TA	donor_gain	1.0000
11:77678151:AAT:A	acceptor_gain	1.0000
11:77678154:C:CA	acceptor_loss	1.0000
11:77678154:C:CC	acceptor_gain	1.0000

AlphaMissense

9603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:77666939:A:T	V1435D	1.000
11:77666951:A:G	L1431P	1.000
11:77676852:A:G	L1094P	1.000
11:77676852:A:T	L1094Q	1.000
11:77676861:A:G	L1091S	1.000
11:77678118:A:C	I1034S	1.000
11:77678118:A:T	I1034N	1.000
11:77678121:G:T	A1033D	1.000
11:77678122:C:G	A1033P	1.000
11:77678130:A:C	I1030S	1.000
11:77678130:A:T	I1030N	1.000
11:77678134:C:G	A1029P	1.000
11:77678139:T:A	D1027V	1.000
11:77678139:T:C	D1027G	1.000
11:77678139:T:G	D1027A	1.000
11:77678140:C:A	D1027Y	1.000
11:77678140:C:G	D1027H	1.000
11:77678141:A:C	F1026L	1.000
11:77678141:A:T	F1026L	1.000
11:77678142:A:C	F1026C	1.000
11:77678142:A:G	F1026S	1.000
11:77678143:A:G	F1026L	1.000
11:77678150:A:C	F1023L	1.000
11:77678150:A:T	F1023L	1.000
11:77678151:A:C	F1023C	1.000
11:77678151:A:G	F1023S	1.000
11:77678152:A:G	F1023L	1.000
11:77683714:A:C	Y1021D	1.000
11:77683714:A:G	Y1021H	1.000
11:77683733:T:A	R1014S	1.000

dbSNP variants (sampled 300 via entrez): RS1000003919 (11:77820697 T>C), RS1000014426 (11:77731928 G>A,C), RS1000025307 (11:77796674 G>A), RS1000046698 (11:77796876 G>C), RS1000050575 (11:77814752 T>C), RS1000068574 (11:77718308 GA>G,GAA), RS1000101202 (11:77837264 T>C), RS1000108094 (11:77712899 A>C), RS1000113619 (11:77846393 C>A,T), RS1000115831 (11:77668356 A>C), RS1000129870 (11:77737561 C>T), RS1000132470 (11:77797513 A>G), RS1000138313 (11:77695456 G>A), RS1000180370 (11:77849260 C>T), RS1000196576 (11:77748321 C>A,T)

Disease associations

OMIM: gene MIM:608522 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007277_15	Tourette syndrome	5.000000e-06
GCST90013421_8	Left-handedness	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

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

Variant	Therapy	Indication	Effect	Level	CIViC
RSF1 Amplification	Tamoxifen	Breast Cancer	Resistance	CIViC B	EID857

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	increases expression	1
Caffeine	affects phosphorylation	1
Clozapine	affects cotreatment, decreases expression	1
Coumestrol	decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8P0	Abcam HCT 116 RSF1 KO	Cancer cell line	Male
CVCL_B9BA	Abcam MCF-7 RSF1 KO	Cancer cell line	Female
CVCL_B9RC	Abcam A-549 RSF1 KO	Cancer cell line	Male
CVCL_E2JL	HAP1 RSF1 (-)	Cancer cell line	Male
CVCL_ZV62	TC587	Cancer cell line	Female

Clinical trials (associated diseases)

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