SAFB

Summary

SAFB (scaffold attachment factor B, HGNC:10520) is a protein-coding gene on chromosome 19p13.3, encoding Scaffold attachment factor B1 (Q15424). Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a ’transcriptosomal’ complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing.

This gene encodes a DNA-binding protein which has high specificity for scaffold or matrix attachment region DNA elements (S/MAR DNA). This protein is thought to be involved in attaching the base of chromatin loops to the nuclear matrix but there is conflicting evidence as to whether this protein is a component of chromatin or a nuclear matrix protein. Scaffold attachment factors are a specific subset of nuclear matrix proteins (NMP) that specifically bind to S/MAR. The encoded protein is thought to serve as a molecular base to assemble a ’transcriptosome complex’ in the vicinity of actively transcribed genes. It is involved in the regulation of heat shock protein 27 transcription, can act as an estrogen receptor co-repressor and is a candidate for breast tumorigenesis. This gene is arranged head-to-head with a similar gene whose product has the same functions. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6294 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 122 total
• MANE Select transcript: NM_001201338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10520
Approved symbol	SAFB
Name	scaffold attachment factor B
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HET, SAFB1
Ensembl gene	ENSG00000160633
Ensembl biotype	protein_coding
OMIM	602895
Entrez	6294

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 35 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000292123, ENST00000454510, ENST00000586281, ENST00000586934, ENST00000588852, ENST00000589006, ENST00000589863, ENST00000590485, ENST00000591666, ENST00000591991, ENST00000592224, ENST00000592396, ENST00000592555, ENST00000592707, ENST00000880693, ENST00000880694, ENST00000880695, ENST00000880696, ENST00000880697, ENST00000880698, ENST00000880699, ENST00000880700, ENST00000934687, ENST00000934688, ENST00000934689, ENST00000934690, ENST00000934691, ENST00000970172, ENST00000970173, ENST00000970174, ENST00000970175, ENST00000970176, ENST00000970177, ENST00000970178, ENST00000970179, ENST00000970180, ENST00000970181, ENST00000970182, ENST00000970183, ENST00000970184, ENST00000970185, ENST00000970186, ENST00000970187, ENST00000970188

RefSeq mRNA: 6 — MANE Select: NM_001201338 NM_001201338, NM_001201339, NM_001201340, NM_001320571, NM_001320572, NM_002967

CCDS: CCDS12142, CCDS56077, CCDS59339, CCDS59340

Canonical transcript exons

ENST00000588852 — 21 exons

Exon	Start	End
ENSE00001616320	5661518	5661808
ENSE00002252185	5623083	5623394
ENSE00003487987	5650978	5651072
ENSE00003520780	5667820	5667886
ENSE00003525171	5667046	5667164
ENSE00003529023	5654368	5654456
ENSE00003529227	5648016	5648043
ENSE00003539095	5641594	5641658
ENSE00003559106	5641740	5641946
ENSE00003583739	5653115	5653264
ENSE00003586786	5649926	5649975
ENSE00003602417	5664022	5664159
ENSE00003622280	5626405	5626489
ENSE00003630795	5653338	5653420
ENSE00003636475	5667347	5667450
ENSE00003636891	5657241	5657347
ENSE00003646475	5648989	5649499
ENSE00003656945	5668162	5668478
ENSE00003667339	5664397	5664439
ENSE00003686459	5645337	5645399
ENSE00003691908	5654061	5654200

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.7823 / max 1546.9802, expressed in 1828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173411	78.6131	1828
173412	1.6114	683
173413	0.5578	302

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.25	gold quality
right uterine tube	UBERON:0001302	98.07	gold quality
endocervix	UBERON:0000458	97.53	gold quality
ventricular zone	UBERON:0003053	97.51	gold quality
cerebellar hemisphere	UBERON:0002245	97.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.46	gold quality
cerebellar cortex	UBERON:0002129	97.42	gold quality
right ovary	UBERON:0002118	97.34	gold quality
left ovary	UBERON:0002119	97.33	gold quality
body of uterus	UBERON:0009853	97.27	gold quality
skin of leg	UBERON:0001511	97.26	gold quality
skin of abdomen	UBERON:0001416	97.22	gold quality
ganglionic eminence	UBERON:0004023	97.22	gold quality
tibial nerve	UBERON:0001323	97.17	gold quality
mucosa of stomach	UBERON:0001199	96.98	gold quality
cerebellum	UBERON:0002037	96.96	gold quality
adenohypophysis	UBERON:0002196	96.94	gold quality
embryo	UBERON:0000922	96.92	gold quality
right lobe of thyroid gland	UBERON:0001119	96.89	gold quality
ectocervix	UBERON:0012249	96.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.78	gold quality
left lobe of thyroid gland	UBERON:0001120	96.64	gold quality
right lung	UBERON:0002167	96.57	gold quality
metanephros cortex	UBERON:0010533	96.57	gold quality
spleen	UBERON:0002106	96.55	gold quality
cortical plate	UBERON:0005343	96.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.53	gold quality
pituitary gland	UBERON:0000007	96.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.17
E-MTAB-6379	no	293.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, E2F1, ESR1, EZH2

miRNA regulators (miRDB)

24 targeting SAFB, 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-12121	99.99	66.64	255
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-744-3P	97.99	67.76	637
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-103B	95.51	66.85	441
HSA-MIR-885-3P	95.14	63.08	448

Literature-anchored findings (GeneRIF, showing 35)

• HSP27 is a nuclear speckle component in unstressed cells in tissue culture. It is also associated with the nucleolar compartment. (PMID:12837281)
• REVIEW: possibility that SAFB1 and SAFB2 are novel breast tumor suppressor genes, and how they might function in this role, are discussed (PMID:14587024)
• HSP27 expression may have useful diagnostic use for the prognosis of mouth squamous cell carcinoma. (PMID:14702179)
• SAFB1 represses ERalpha activity via indirect association with histone deacetylation and interaction with the basal transcription machinery (PMID:15066997)
• SAFB1 was shown to interact directly with the nuclear receptor corepressor N-CoR. (PMID:16195251)
• SAFB1 interacts in pull-down assays not only with PPARgamma but also with all nuclear receptors tested (PMID:16326836)
• PP2A-mediated dephosphorylation of HSP27 and tau correlated with PP2A-induced preservation of endothelial cell cytoskeleton (PMID:16475161)
• SAFB may direct the reorganization and segregation of nuclear RNA and DNA prior to endonuclease-mediated DNA cleavage. (PMID:17643427)
• Over expression of HSP27 is associated with intrahepatic cholangiocarcinoma (PMID:18154639)
• hXOR is a tumor suppressor-targeted gene and the phosphorylation of SAFB1 is regulated by OSM, which provides a molecular basis for understanding the role of SAFB1-regulated hXOR transcription in cytokine stimulation and tumorigenesis (PMID:18772145)
• SAFB1 is not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families (PMID:19077293)
• Importance of ERE-BP as an attenuator of normal ERalpha signaling in vivo and is a novel target for modulation by selective estrogen receptor modulators. (PMID:19106221)
• This study shows that low SAFB protein levels predict poor prognosis of breast cancer patients, suggesting critical functions of SAFB1 and SAFB2 in breast cancer cells. (PMID:19137425)
• The enzymatic activity of SR protein kinases 1 and 1a is negatively affected by interaction with scaffold attachment factors B1 and 2. (PMID:19674106)
• Study confirms the primary role of SAFB1/SAFB2 as corepressors and also uncovers a previously unknown role for SAFB1 in the regulation of immune genes and in estrogen-mediated repression of genes. (PMID:19901029)
• Data show that binding of p53 to SAFB1 had a significant functional outcome, since SAFB1 was shown to suppress p53-mediated reporter gene expression. (PMID:21130767)
• transcriptional repressor SAFB1 is modified by both SUMO1 and SUMO2/3, and this modification is necessary for its full repressive activity. (PMID:21527249)
• Results indicate that SAFB1 and SAFB2 are crucial repressors for ERalpha dynamics in association with the nuclear matrix and that their synergistic regulation of ERalpha mobility is sufficient for inhibiting ERalpha function. (PMID:22566185)
• SAFB1 formed a complex with the histone methyltransferase EZH2. (PMID:23893242)
• Data indicate that scaffold attachment factor SAFB1 is transiently recruited to DNA breaks in a poly(ADP-ribose)-polymerase 1- and poly(ADP-ribose)-dependent manner. (PMID:24055346)
• reveals an unexpected role of SUMO-1 and SAFB in the stimulatory coupling of promoter binding, transcription initiation and RNA processing (PMID:25800734)
• Single depletion of either SAFB1 or SAFB2 leads to an increase in expression of the other SAFB protein. (PMID:26273616)
• The expression of coding and non-coding genes with SAFB1 cross-link sites was altered by SAFB1 knockdown. The isoform-specific expression of neural cell adhesion molecule (NCAM1) and ASTN2 was influenced by SAFB1. (PMID:26694817)
• Depletion of SAFB1 reduced FUS’s localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif. Moreover, FUS interacts with another nuclear matrix-associated protein, Matrin3. (PMID:27731383)
• Data suggest that ERH interacts directly in nucleus with C-terminal Arg-Gly-rich region of SAFB1/SAFB2 and this multimer co-localizes in insoluble nuclear fraction; binding of ERH reverses inhibition exerted by SAFB1/SAFB2 on SRPK1. (ERH = enhancer of rudimentary homolog protein; SAFB = scaffold attachment factor B; SRPK1 = splicing kinase SR protein kinase-1) (PMID:28627136)
• SAFB regulated the activity of NF-kappaB signaling in CRC by targeting TAK1 This novel mechanism provides a comprehensive understanding of both SAFB and the NF-kappaB signaling pathway in the progression of CRC and indicates that the SAFB-TAK1-NF-kappaB axis is a potential target for early therapeutic intervention in CRC progression (PMID:28912140)
• SAFB1 binds to the HIV-1 LTR and physically interacts with phosphorylated RNA polymerase II, repressing HIV-1 transcription initiation and elongation. (PMID:29887524)
• Depletion of SAFB leads to changes in 3D genome organization. (PMID:31677973)
• Abnormal scaffold attachment factor 1 expression and localization in spinocerebellar ataxias and Huntington’s chorea. (PMID:32580238)
• Scaffold association factor B (SAFB) is required for expression of prenyltransferases and RAS membrane association. (PMID:33257571)
• Inhibition of HSF1 and SAFB Granule Formation Enhances Apoptosis Induced by Heat Stress. (PMID:34067147)
• Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1. (PMID:34129097)
• Short-term hypoxia triggers ROS and SAFB mediated nuclear matrix and mRNA splicing remodeling. (PMID:36427398)
• SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma. (PMID:36462498)
• HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia. (PMID:36577137)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	safb	ENSDARG00000020467
mus_musculus	Safb	ENSMUSG00000071054
rattus_norvegicus	Safb	ENSRNOG00000050543
drosophila_melanogaster	Saf-B	FBGN0039229
caenorhabditis_elegans	phm-2	WBGENE00009314

Paralogs (2): SAFB2 (ENSG00000130254), SLTM (ENSG00000137776)

Protein

Protein identifiers

Scaffold attachment factor B1 — Q15424 (reviewed: Q15424)

Alternative names: HSP27 estrogen response element-TATA box-binding protein

All UniProt accessions (3): Q15424, K7EII0, K7ES42

UniProt curated annotations — full annotation on UniProt →

Function. Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a ’transcriptosomal’ complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing. Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription. Thereby acts as a negative regulator of cell proliferation. When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter.

Subunit / interactions. Monomer and homodimer. Forms heterodimers with SAFB2. Interacts with KHDRBS3. Interacts with CLK2. Interacts with POLR2A, SRSF1/ASF, SRSF9/SRp30c and SFSF10/TRA2B. Interacts with isoform 1 and isoform 2 of SRPK1 and inhibits its activity. Interacts with RBMX. Interacts with FUS. Interacts with ZBED4.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Expressed at high levels in the CNS and at low levels in the liver. Expressed in a wide number of breast cancer cell lines.

Post-translational modifications. Sumoylated by PIAS1 with SUMO1 and SUMO2/3, desumoylated by SENP1. Sumoylation is required for transcriptional repressor activity.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15424-1	1	yes
Q15424-2	2
Q15424-3	3
Q15424-4	4

RefSeq proteins (6): NP_001188267, NP_001188268, NP_001188269, NP_001307500, NP_001307501, NP_002958 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003034	SAP_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034781	SAFB1_2_RBD	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR051738	SAF_Modulators	Family

Pfam: PF00076, PF02037

UniProt features (74 total): modified residue 20, compositionally biased region 18, cross-link 13, region of interest 8, sequence conflict 7, splice variant 3, domain 2, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15424-F1	54.83	0.14

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 (33): 2, 24, 55, 79, 188, 195, 197, 209, 383, 384, 415, 580, 582, 601, 604, 607, 811, 868, 874, 884 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 168 (showing top): RNGTGGGC_UNKNOWN, MORF_DNMT1, TGCGCANK_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_LIPID, MORF_SNRP70, MORF_RRM1, MORF_HDAC2, MORF_TERF1, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MORF_BUB3, MORF_RFC4, MORF_PRKDC, GCM_NUMA1, GOBP_RESPONSE_TO_STEROID_HORMONE

GO Biological Process (5): chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), estrogen receptor signaling pathway (GO:0030520), regulation of mRNA processing (GO:0050684), regulation of androgen receptor signaling pathway (GO:0060765)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), sequence-specific DNA binding (GO:0043565), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), midbody (GO:0030496)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
DNA binding	2
nucleic acid binding	2
cellular anatomical structure	2
cellular component organization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
nuclear receptor-mediated steroid hormone signaling pathway	1
mRNA processing	1
regulation of mRNA metabolic process	1
androgen receptor signaling pathway	1
regulation of intracellular steroid hormone receptor signaling pathway	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAFB	TJP2	Q9UDY2	957
SAFB	ESR1	P03372	815
SAFB	YTHDC1	Q96MU7	745
SAFB	SORBS3	O60504	730
SAFB	HNRNPU	Q00839	725
SAFB	SRSF1	Q07955	709
SAFB	TJP3	O95049	709
SAFB	RBMX	P38159	679
SAFB	KHDRBS1	Q07666	643
SAFB	SRPK1	Q96SB4	595
SAFB	ERH	P70659	570
SAFB	HSPB2	Q16082	566
SAFB	HSPB1	P04792	558
SAFB	CLDN8	P56748	549
SAFB	HSPB3	Q12988	532

IntAct

191 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
FUS	SAFB	psi-mi:“MI:0915”(physical association)	0.730
FUS	SAFB	psi-mi:“MI:0403”(colocalization)	0.730
FUS	MATR3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
SAFB	TP53	psi-mi:“MI:0915”(physical association)	0.560
SAFB	TP53	psi-mi:“MI:0403”(colocalization)	0.560
TP53	SAFB	psi-mi:“MI:0915”(physical association)	0.560
MAP1LC3B	SAFB	psi-mi:“MI:0915”(physical association)	0.550
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
ELAVL2	CASC3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SRSF3	CASC3	psi-mi:“MI:0914”(association)	0.530
LRRK2	DFFA	psi-mi:“MI:0914”(association)	0.530
SAFB	SRPK1	psi-mi:“MI:0915”(physical association)	0.520
SRPK1	SAFB	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (324): SAFB (Affinity Capture-MS), SAFB (Affinity Capture-MS), SAFB (Affinity Capture-MS), SAFB (Two-hybrid), TP53 (Affinity Capture-Western), SAFB (Affinity Capture-Western), SAFB (Affinity Capture-MS), SAFB (Two-hybrid), SAFB (Affinity Capture-MS), SAFB (Affinity Capture-RNA), SAFB (Affinity Capture-MS), HNRNPU (Co-fractionation), HNRNPUL1 (Co-fractionation), MCM4 (Co-fractionation), P4HB (Co-fractionation)

ESM2 similar proteins: A0A0R4IZ84, A2CEZ5, A2RV70, D3YXK2, F1MJM0, O15047, O43823, O60293, O88291, O88453, P41073, P43243, P43244, P61129, P61406, P78332, P97868, Q08D57, Q14151, Q15424, Q1LY77, Q28F29, Q2HJG4, Q3TLH4, Q498L2, Q5BKZ1, Q5F3P8, Q5R452, Q5RAK6, Q5RCA4, Q5U236, Q5VK71, Q5ZJ02, Q63014, Q66HC1, Q66J90, Q7YZA2, Q7Z6E9, Q80YR5, Q86US8

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A2A5N3, D3YXK2, G5EFS2, O22703, O74400, O88453, P10979, P19682, P19683, P28644, P39697, P49310, P49313, P49314, P82277, Q03251, Q04836, Q05966, Q08935, Q08937, Q10422, Q14151, Q15424, Q28IQ9, Q43349, Q43472, Q498L2, Q54Y98, Q5R452, Q6IQ97, Q80YR5, Q84TH4, Q8CH25, Q8VYM4, Q94901, Q99069, Q99070, Q9C909

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SAFB	“up-regulates activity”	FUS	relocalization
BRCA1	“up-regulates quantity by stabilization”	SAFB	ubiquitination
STK4	“down-regulates activity”	SAFB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 215 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
Transport of Mature Transcript to Cytoplasm	7	17.8×	8e-06
mRNA 3’-end processing	12	15.8×	2e-09
RNA Polymerase II Transcription Termination	9	13.2×	2e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	12	12.2×	3e-08
mRNA Polyadenylation	18	10.5×	2e-11
Processing of Capped Intron-Containing Pre-mRNA	19	10.4×	1e-11
mRNA Splicing	14	10.2×	1e-08
mRNA Splicing - Major Pathway	22	8.0×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	27.9×	2e-06
positive regulation of transcription by RNA polymerase III	5	24.4×	2e-04
activation of innate immune response	8	20.1×	2e-06
mRNA export from nucleus	9	13.9×	4e-06
cellular response to interferon-beta	5	13.7×	3e-03
regulation of alternative mRNA splicing, via spliceosome	10	12.7×	2e-06
mitophagy	6	9.9×	3e-03
mRNA splicing, via spliceosome	18	8.6×	5e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2651 predictions. Top by Δscore:

Variant	Effect	Δscore
19:5623392:AAG:A	donor_loss	1.0000
19:5623393:AGGT:A	donor_loss	1.0000
19:5623394:GG:G	donor_loss	1.0000
19:5626401:TTAG:T	acceptor_loss	1.0000
19:5626402:TAG:T	acceptor_loss	1.0000
19:5626403:A:AG	acceptor_gain	1.0000
19:5626403:A:AT	acceptor_loss	1.0000
19:5626403:AG:A	acceptor_gain	1.0000
19:5626404:G:GT	acceptor_gain	1.0000
19:5626404:GG:G	acceptor_gain	1.0000
19:5626404:GGC:G	acceptor_gain	1.0000
19:5626404:GGCA:G	acceptor_gain	1.0000
19:5626486:AAAGG:A	donor_loss	1.0000
19:5626487:AAGGT:A	donor_loss	1.0000
19:5641588:CTTCA:C	acceptor_loss	1.0000
19:5641590:TCA:T	acceptor_loss	1.0000
19:5641591:CA:C	acceptor_loss	1.0000
19:5641593:G:GT	acceptor_loss	1.0000
19:5641734:TCACA:T	acceptor_loss	1.0000
19:5641735:CACA:C	acceptor_loss	1.0000
19:5641737:CA:C	acceptor_loss	1.0000
19:5641738:A:G	acceptor_loss	1.0000
19:5641738:AGGAG:A	acceptor_gain	1.0000
19:5641739:G:GA	acceptor_loss	1.0000
19:5641739:GGAGG:G	acceptor_gain	1.0000
19:5641938:G:GT	donor_gain	1.0000
19:5641939:A:T	donor_gain	1.0000
19:5641942:ATGCT:A	donor_gain	1.0000
19:5641943:TGCT:T	donor_gain	1.0000
19:5641944:GCT:G	donor_gain	1.0000

AlphaMissense

6066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5623306:T:C	L34P	1.000
19:5623321:T:A	L39Q	1.000
19:5623321:T:C	L39P	1.000
19:5623333:T:C	L43P	1.000
19:5623365:A:G	K54E	1.000
19:5623367:G:C	K54N	1.000
19:5623367:G:T	K54N	1.000
19:5623375:T:C	L57S	1.000
19:5623387:T:C	L61P	1.000
19:5651004:T:A	W409R	1.000
19:5651004:T:C	W409R	1.000
19:5651006:G:C	W409C	1.000
19:5651006:G:T	W409C	1.000
19:5651008:T:A	V410D	1.000
19:5651017:T:A	L413H	1.000
19:5651017:T:C	L413P	1.000
19:5651035:C:A	A419D	1.000
19:5651044:T:C	L422S	1.000
19:5651044:T:G	L422W	1.000
19:5651046:A:G	K423E	1.000
19:5651048:G:C	K423N	1.000
19:5651048:G:T	K423N	1.000
19:5651053:T:C	L425P	1.000
19:5651055:T:C	F426L	1.000
19:5651057:C:A	F426L	1.000
19:5651057:C:G	F426L	1.000
19:5651067:G:A	G430R	1.000
19:5651067:G:C	G430R	1.000
19:5651067:G:T	G430W	1.000
19:5651068:G:A	G430E	1.000

dbSNP variants (sampled 300 via entrez): RS1000124593 (19:5652732 T>C), RS1000153643 (19:5636226 C>T), RS1000160896 (19:5637617 A>G), RS1000277445 (19:5658142 C>T), RS1000371187 (19:5622744 C>G,T), RS1000387772 (19:5652978 G>A), RS1000432832 (19:5642910 G>A,C), RS1000436371 (19:5635324 C>T), RS1000462843 (19:5651536 G>A,T), RS1000494675 (19:5636275 T>C), RS1000505482 (19:5663264 G>A), RS1000548468 (19:5636460 A>G,T), RS1000670898 (19:5641468 A>G), RS1000721035 (19:5645308 G>A,T), RS1000723757 (19:5651782 C>G,T)

Disease associations

OMIM: gene MIM:602895 | 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
GCST90002396_13	Mean reticulocyte volume	7.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Fulvestrant	decreases reaction, increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
arsenite	decreases reaction, increases expression, decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
bisphenol AF	increases expression	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	increases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	decreases reaction, increases expression	1
Caffeine	affects phosphorylation	1

Clinical trials (associated diseases)

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