PSIP1

Summary

PSIP1 (PC4 and SRSF1 interacting protein 1, HGNC:9527) is a protein-coding gene on chromosome 9p22.3, encoding PC4 and SFRS1-interacting protein (O75475). Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis.

Enables DNA-binding transcription factor binding activity; chromatin binding activity; and transcription coactivator activity. Involved in mRNA 5’-splice site recognition and positive regulation of transcription by RNA polymerase II. Located in heterochromatin; nuclear periphery; and nucleoplasm.

Source: NCBI Gene 11168 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_033222

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9527
Approved symbol	PSIP1
Name	PC4 and SRSF1 interacting protein 1
Location	9p22.3
Locus type	gene with protein product
Status	Approved
Aliases	p52, LEDGF, p75, DFS70
Ensembl gene	ENSG00000164985
Ensembl biotype	protein_coding
OMIM	603620
Entrez	11168

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000380715, ENST00000380716, ENST00000380733, ENST00000380738, ENST00000397519, ENST00000463712, ENST00000481862, ENST00000484265, ENST00000487363, ENST00000488797, ENST00000495873, ENST00000901729, ENST00000901730, ENST00000901731, ENST00000901732, ENST00000901733, ENST00000917556, ENST00000917557, ENST00000917558, ENST00000917559, ENST00000917560, ENST00000917561, ENST00000950211, ENST00000950212, ENST00000950213, ENST00000950214, ENST00000950215

RefSeq mRNA: 5 — MANE Select: NM_033222 NM_001128217, NM_001317898, NM_001317900, NM_021144, NM_033222

CCDS: CCDS6479, CCDS6480, CCDS83348

Canonical transcript exons

ENST00000380733 — 16 exons

Exon	Start	End
ENSE00001089131	15466748	15466859
ENSE00001132806	15468630	15468843
ENSE00001132811	15468957	15469058
ENSE00001132819	15469266	15469336
ENSE00001132824	15469938	15469993
ENSE00001132838	15474009	15474237
ENSE00001132844	15478477	15478552
ENSE00001132852	15479591	15479687
ENSE00001132860	15486006	15486068
ENSE00001486085	15464066	15465580
ENSE00001824708	15510817	15510970
ENSE00003487981	15486827	15486931
ENSE00003528129	15489986	15490124
ENSE00003586740	15506561	15506637
ENSE00003625642	15510117	15510329
ENSE00003711429	15472632	15472750

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.3555 / max 1263.1181, expressed in 1804 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100082	56.7359	1794
100081	1.5287	534
100080	0.9984	529
100078	0.7209	290
100075	0.5742	269
100079	0.3669	165
100076	0.2469	117
100084	0.1837	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.40	gold quality
ventricular zone	UBERON:0003053	99.37	gold quality
ganglionic eminence	UBERON:0004023	99.10	gold quality
cortical plate	UBERON:0005343	98.75	gold quality
cerebellar hemisphere	UBERON:0002245	98.64	gold quality
cerebellar cortex	UBERON:0002129	98.62	gold quality
embryo	UBERON:0000922	98.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.51	gold quality
cerebellum	UBERON:0002037	98.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.82	gold quality
calcaneal tendon	UBERON:0003701	97.79	gold quality
cranial nerve II	UBERON:0000941	97.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.66	gold quality
nucleus accumbens	UBERON:0001882	97.65	gold quality
right frontal lobe	UBERON:0002810	97.58	gold quality
oocyte	CL:0000023	97.52	gold quality
prefrontal cortex	UBERON:0000451	97.52	gold quality
caudate nucleus	UBERON:0001873	97.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.37	gold quality
amygdala	UBERON:0001876	97.24	gold quality
mucosa of stomach	UBERON:0001199	97.14	gold quality
spinal cord	UBERON:0002240	97.07	gold quality
hypothalamus	UBERON:0001898	97.00	gold quality
sural nerve	UBERON:0015488	96.97	gold quality
putamen	UBERON:0001874	96.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.83	gold quality
ovary	UBERON:0000992	96.73	gold quality
blood vessel layer	UBERON:0004797	96.72	gold quality
descending thoracic aorta	UBERON:0002345	96.56	gold quality
cingulate cortex	UBERON:0003027	96.56	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	350.97
E-GEOD-134144	yes	26.88
E-GEOD-125970	yes	16.79
E-MTAB-9388	yes	14.10
E-MTAB-5061	yes	13.14
E-ANND-3	yes	8.55
E-GEOD-81608	yes	5.94
E-CURD-88	yes	5.41
E-GEOD-81547	yes	5.35
E-ENAD-27	yes	4.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, FOXC1, HDAC1, NFKB2, NONO, SP1, TCF3

miRNA regulators (miRDB)

136 targeting PSIP1, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• LEDGF/p75 protected cells from cell death, whereas the 65 kD fragment failed to protect. The apoptotic cleavage of LEDGF/p75 may cause atopic disorders by abrogating its pro-survival function and enhancing its immunogenicity. (PMID:12181742)
• HIV-1 integrase associates with LEDGF/p75 in human cells. Integrase co-localizes with endogenous LEDGF/p75 in nuclei and on condensed chromosomes in mitotic cells. LEDGF/p75 stimulates integrase activity in vitro. (PMID:12407101)
• the interaction with LEDGF/p75 accounts for the karyophilic properties and chromosomal targeting of HIV-1 integrase (PMID:12796494)
• lens epithelium-derived growth factor (LEDGF)/p75 LEDGF/p75 NLS, 148GRKRKAEKQ156, belongs to the canonical SV40 large T antigen-like family nuclear localization signal (NLS) (PMID:15163664)
• LEDGF/p75 fully accounts for cellular trafficking of diverse lentiviral, but not oncoretroviral, integrases and is the main lentiviral integrase-to-chromatin tethering factor (PMID:15308744)
• LEDGF/p75 and HRP2 IBDs avidly bind HIV-1 Integrase, share a similar domain organization and have an evident evolutionary and likely functional relationship (PMID:15371438)
• Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase (PMID:15475359)
• Circular dichroism analysis revealed that DFS(349-435) contains an approximately 40% alpha-helical conformation (PMID:15501393)
• autoantibodies against the DFS70 are related to the etiology in a certain population of Alopecia areata (PMID:15501396)
• A novel fusion of the NUP98 and LEDGF genes in a pediatric case of acute myeloid leukemia. (PMID:15725483)
• Whereas LEDGF/p75 displayed only a moderate affinity for DNA, it strongly promoted the binding of HIV-1 integrase to DNA. This effect was specific for the p75 isoform of LEDGF and was not seen with p52. (PMID:15749713)
• LEDGF/p75 is a multidomain adaptor protein that interacts with the nuclear import apparatus, lentiviral IN proteins and chromatin by means of an NLS, an IBD and additional chromatin-interacting domains. (PMID:15797927)
• LEDGF/p75 tethers HIV-1 integrase to chromosomes and that this interaction may be important for the integration process and the replication of HIV-1 (PMID:15855167)
• LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells. (PMID:16311605)
• Here, we show that recombinant LEDGF host cell factor efficiently reconstitutes the in vitro activity of HIV-1 preintegration complexes. (PMID:16337983)
• Results suggest that TNF-alpha elevates the expression of lens epithelium-derived growth factor (LEDGF) and that LEDGF is one of the transactivators of gamma-glutamylcysteine synthetase heavy subunit gene. (PMID:16403949)
• data validate LEDGF/p75 as an important cellular cofactor for HIV integration (PMID:16439544)
• LEDGF (PSIP1) binds and tethers the Myc-interacting protein JPO2/RAM2 to chromatin. (PMID:16735438)
• The role for p75 in the Myc regulatory network, and indicate that p75 is a general adaptor protein tethering divergent factors to chromatin through its versatile integrase-binding domain. (PMID:16735438)
• The results establish a molecular mechanism for LEDGF/p75-mediated tethering of HIV-1 integrase to chromatin. (PMID:16793062)
• findings show that (LEDGF)/p75 (p75) is an essential HIV integration cofactor; the mechanism requires both linkages of a molecular tether that p75 forms between integrase and chromatin (PMID:16959972)
• Our data show that LEDGF differentially affects HIV-1 integrase-DNA complexes mediating single-ended viral DNA integration and synaptic complexes mediating concerted integration. (PMID:17267486)
• The complementary inhibition by LEDGF/p75 knockdown and mutagenesis at the integrase-LEDGF/p75 interface points to the incapability of HIV to circumvent LEDGF/p75 function during proviral integration. (PMID:17397262)
• Analysis of blasts from single patients disclosed that LEDGF/p75 was the most consistently upregulated mRNA in resistant acute myelogenous leukemia. (PMID:17451600)
• Over-expression of JPO2 resulted in a modest but reproducible inhibition of HIV-1 replication, consistent with competition between integrase and JPO2 for binding to LEDGF/p75 (PMID:17669426)
• some DFS70-positive sera have antibodies that recognize antigens of the lens (PMID:17804545)
• Furthermore, results indicate that induction of apoptosis in HCT-116 p53(wt) cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75(NTR), p53 and Bax. (PMID:18036557)
• it could be suggested that residues Gln168, Glu170, and Thr174 in chain A of IN, Thr125, and Trp131 in chain B of IN as well as Ile365, Asp366, Phe406, and Val408 in LEDGF/p75 were responsible for their binding with HIV-1 integrase (PMID:18247352)
• LEDGF critically associates with mixed-lineage leukemia protein and menin at the nexus of transcriptional pathways that are recurrently targeted in diverse diseases. (PMID:18598942)
• LEDGF/p75 and p52 seem to play antagonistic roles in the cellular stress response and could serve as targets for novel antitumor therapies. (PMID:18708362)
• a number of PWWP domain residues, highlighted by Trp-21 and Ala-51, which play critical roles in LEDGF/p75-dependent HIV-1 infection and integration. (PMID:18799576)
• structural basis for the high affinity lentiviral IN-LEDGF interaction (PMID:19132083)
• A functional complex between the wild-type full-length integrase (IN) and the cellular cofactor LEDGF/p75 showed enhanced in vitro integration activity compared with the integrase alone. (PMID:19229293)
• LEDGF/p75 has a role in DDE domain protein function and interacts with the transposase-derived DDE domain of PogZ (PMID:19244240)
• Results point to LEDGF/p75 as a potential contributor to cellular resistance to docetaxel-induced lysosomal destabilization and cell death, and an attractive candidate for molecular targeting in HRPC. (PMID:19715609)
• Study revealed the significantly tighter nature of the IN-IN dimer compared with the IN-LEDGF interaction. (PMID:19801648)
• Results show that HIV-1 Rev promotes dissociation of the IN-LEDGF/p75 complex. Combination of the viral IN and the cellular LEDGF/p75 is required for proper integration of the viral cDNA into the host chromosomal DNA. (PMID:19855849)
• The interaction with LEDGF relieves autoinhibition of Cdc7-ASK kinase, imposed by the C terminus of ASK. (PMID:19864417)
• These results clearly indicated that serine residues 271, 273, and 275 influence the HIV-1 cofactor activity of integrase-to-chromatin-tethering-competent LEDGF/p75. (PMID:19889764)
• Chromatin immunoprecipitation showed that LEDGF/p75 binds the VEGF-C promoter, and binding is augmented by FSH. A corresponding hormonally regulated increase in the LEDGF/p75 mRNA and protein levels was observed. (PMID:19934313)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	psip1b	ENSDARG00000077405
danio_rerio	psip1a	ENSDARG00000104710
mus_musculus	Psip1	ENSMUSG00000028484
rattus_norvegicus	Psip1	ENSRNOG00000011498

Paralogs (4): HDGFL1 (ENSG00000112273), HDGF (ENSG00000143321), HDGFL3 (ENSG00000166503), HDGFL2 (ENSG00000167674)

Protein

Protein identifiers

PC4 and SFRS1-interacting protein — O75475 (reviewed: O75475)

Alternative names: CLL-associated antigen KW-7, Dense fine speckles 70 kDa protein, Lens epithelium-derived growth factor, Transcriptional coactivator p75/p52

All UniProt accessions (2): O75475, V9GYT7

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.

Subunit / interactions. Monomer. Interacts with IFRD1/PC4. Isoform 2 interacts with SFRS1. Isoform 1 interacts (via IBD domain) with POGZ (via IBM motif) and CDCA7L (via IBM motifs). Interacts (via IBD domain) with KMT2A (via IBM motifs) with a moderate affinity whereas interacts with the KMT2A-MEN1 complex with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1. Interacts with fusion protein KMT2A-MLLT3. Interacts (via IBD domain) with IWS1 (via IBM motif), MED1 (via IBM motif) and DBF4 (via IBM motifs). (Microbial infection) Interacts (via IBD domain) with human HIV-1 integrase protein (HIV-1 IN), determining its nuclear localization, its tight association with chromatin and its protection from the proteasome. (Microbial infection) Interacts with HIV-2 IN.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Expressed at high level in the thymus. Expressed in fetal and adult brain. Expressed in neurons, but not astrocytes. Markedly elevated in fetal as compared to adult brain. In the adult brain, expressed in the subventricular zone (SVZ), in hippocampus, and undetectable elsewhere. In the fetal brain, expressed in the germinal neuroepithelium and cortical plate regions.

Post-translational modifications. Citrullinated by PADI4.

Disease relevance. A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1 exon 4.

Miscellaneous. Less active than isoform 2 as transcriptional coactivator, but more abundant in cells.

Similarity. Belongs to the HDGF family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75475-1	1, p75, PSIP1	yes
O75475-2	2, p52, PSIP2
O75475-3	3

RefSeq proteins (5): NP_001121689, NP_001304827, NP_001304829, NP_066967, NP_150091* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000313	PWWP_dom	Domain
IPR021567	LEDGF_IBD	Domain
IPR035441	TFIIS/LEDGF_dom_sf	Homologous_superfamily
IPR036218	HIVI-bd_sf	Homologous_superfamily

Pfam: PF00855, PF11467

UniProt features (80 total): modified residue 21, helix 12, mutagenesis site 11, compositionally biased region 10, strand 9, sequence conflict 4, region of interest 3, splice variant 3, coiled-coil region 2, chain 1, domain 1, cross-link 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6TRJ	X-RAY DIFFRACTION	1.3
5N88	X-RAY DIFFRACTION	1.7
2B4J	X-RAY DIFFRACTION	2.02
5OYM	X-RAY DIFFRACTION	2.05
4FU6	X-RAY DIFFRACTION	2.1
3HPH	X-RAY DIFFRACTION	2.64
8PEO	ELECTRON MICROSCOPY	2.69
3U88	X-RAY DIFFRACTION	3
7OUF	ELECTRON MICROSCOPY	3
8PC5	ELECTRON MICROSCOPY	3.02
8PC6	ELECTRON MICROSCOPY	3.04
7OUG	ELECTRON MICROSCOPY	3.1
3F9K	X-RAY DIFFRACTION	3.2
6S01	ELECTRON MICROSCOPY	3.2
3HPG	X-RAY DIFFRACTION	3.28
8PEP	ELECTRON MICROSCOPY	3.33
7PEL	ELECTRON MICROSCOPY	3.34
8CBN	ELECTRON MICROSCOPY	3.34
7OUH	ELECTRON MICROSCOPY	3.5
7Z1Z	ELECTRON MICROSCOPY	3.5
9XYC	ELECTRON MICROSCOPY	3.5
8CBQ	ELECTRON MICROSCOPY	4
9BW9	ELECTRON MICROSCOPY	4.1
1Z9E	SOLUTION NMR
2M16	SOLUTION NMR
2MSR	SOLUTION NMR
2MTN	SOLUTION NMR
2N3A	SOLUTION NMR
3ZEH	SOLUTION NMR
5YI9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75475-F1	63.32	0.30

Antibody-complex structures (SAbDab): 1 — 5N88

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 (22): 102, 105, 106, 115, 122, 129, 141, 167, 177, 206, 271, 272, 273, 275, 434, 437, 443, 514, 517, 522 …

Mutagenesis-validated functional residues (11):

Position	Phenotype
360	reduced interaction with pogz, cdca7l and human hiv-1 integrase.
365	loss of interaction with human hiv-1 integrase; reduced interaction with pogz and cdca7l.
366	loss of interaction with human hiv-1 integrase; no effect on interaction with cdca7l and pogz.
366	loss of interaction with human hiv-1 integrase; no effect on interaction with kmt2a.
368	reduced interaction with kmt2a. significant loss of interaction with kmt2a; when associated with d-407.
370	reduced interaction with pogz, cdca7l and human hiv-1 integrase.
404	significant loss of interaction with kmt2a; when associated with d-405.
405	significant loss of interaction with kmt2a; when associated with d-404.
406	loss of interaction with human hiv-1 integrase and pogz; reduced interaction with cdca7l.
407	reduced interaction with kmt2a. significant loss of interaction with kmt2a; when associated with a-368.
408	reduced interaction with human hiv-1 integrase; no effect on interaction with pogz and cdca7l.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-162592	Integration of provirus
R-HSA-164843	2-LTR circle formation
R-HSA-175567	Integration of viral DNA into host genomic DNA
R-HSA-177539	Autointegration results in viral DNA circles
R-HSA-180689	APOBEC3G mediated resistance to HIV-1 infection
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes

MSigDB gene sets: 352 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, PAX4_01, REACTOME_INTEGRATION_OF_PROVIRUS, RORA1_01, PAL_PRMT5_TARGETS_UP, GCANCTGNY_MYOD_Q6, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, KONG_E2F3_TARGETS, CAGCTG_AP4_Q5, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (5): mRNA 5’-splice site recognition (GO:0000395), chromatin remodeling (GO:0006338), response to oxidative stress (GO:0006979), response to heat (GO:0009408), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), supercoiled DNA binding (GO:0097100), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): euchromatin (GO:0000791), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear periphery (GO:0034399)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Integration of provirus	3
Early Phase of HIV Life Cycle	1
Host Interactions of HIV factors	1
Interactions of Vpr with host cellular proteins	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to stress	2
positive regulation of DNA-templated transcription	2
binding	2
nucleic acid binding	2
chromatin	2
nuclear lumen	2
mRNA splice site recognition	1
mRNA cis splicing, via spliceosome	1
chromatin organization	1
response to temperature stimulus	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
transcription coregulator activity	1
double-stranded DNA binding	1
transcription factor binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSIP1	MEN1	O00255	986
PSIP1	SRSF1	Q07955	953
PSIP1	RBBP8	Q99708	944
PSIP1	RBBP5	Q15291	866
PSIP1	CDCA7L	Q96GN5	848
PSIP1	NUP98	P52948	831
PSIP1	TNPO3	Q9Y5L0	775
PSIP1	KAT5	Q92993	746
PSIP1	DDX10	Q13206	734
PSIP1	NSD1	Q96L73	717
PSIP1	NUP153	P49790	712
PSIP1	BANF2	Q9H503	695
PSIP1	NUP214	P35658	691
PSIP1	HOXA9	P31269	685
PSIP1	SMARCB1	Q12824	684

IntAct

107 interactions, top by confidence:

A	B	Type	Score
KMT2A	MEN1	psi-mi:“MI:0915”(physical association)	0.700
KMT2A	MEN1	psi-mi:“MI:0407”(direct interaction)	0.700
PSIP1	RBBP8	psi-mi:“MI:0915”(physical association)	0.600
PSIP1	RBBP8	psi-mi:“MI:0407”(direct interaction)	0.600
RBBP8	PSIP1	psi-mi:“MI:0915”(physical association)	0.600
KMT2B	MEN1	psi-mi:“MI:0914”(association)	0.460
gag-pol	EIF3F	psi-mi:“MI:0914”(association)	0.460
gag-pol	PSIP1	psi-mi:“MI:0407”(direct interaction)	0.440
PSIP1	gag-pol	psi-mi:“MI:0407”(direct interaction)	0.440
PSIP1	SUMO1	psi-mi:“MI:0914”(association)	0.430

BioGRID (283): PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-RNA), PSIP1 (Proximity Label-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS), PSIP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GR68, A2CG63, E6ZGB4, F7AQ22, F8VPQ2, G3V8T1, O75151, O75376, O75475, O88974, O96028, P29374, Q0VEE6, Q0VGB7, Q15047, Q2TB10, Q3TYA6, Q4KKX4, Q4LE39, Q5F363, Q5HYC2, Q5JSH3, Q5R9U6, Q5XJV7, Q5XXA9, Q5ZMU6, Q60974, Q62315, Q66T72, Q6DCQ0, Q6INA9, Q6NVE8, Q6P7W0, Q6P949, Q6P964, Q812D1, Q8BVE8, Q8MJG1, Q8QG78, Q8VBW5

Diamond homologs: A4FUF0, F4I907, F4K4D6, O75475, P51858, P51859, Q175F8, Q29NG1, Q32N87, Q3UMU9, Q49A26, Q562D5, Q5R7T2, Q5RKH0, Q5RKN4, Q5XXA9, Q5ZLS7, Q66T72, Q6K431, Q6P2L6, Q6P4K1, Q7Q161, Q7Z4V5, Q812D1, Q8MJG1, Q8MT36, Q8T079, Q8VHK7, Q922P9, Q923W4, Q925G1, Q99JF8, Q9BZ95, Q9FNE4, Q9JMG7, Q9LEY4, Q9LSV0, Q9LYZ0, Q9SF36, Q9SZE1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CASP3	down-regulates	PSIP1	cleavage
“Caspase 3 complex”	down-regulates	PSIP1	cleavage
CDC7	up-regulates	PSIP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
PKR-mediated signaling	5	12.6×	7e-03
Formation of the beta-catenin:TCF transactivating complex	5	10.7×	9e-03
Dengue Virus-Host Interactions	8	6.5×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	5	17.2×	2e-03
chromatin organization	7	9.4×	2e-03
DNA repair	8	6.9×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — BLCA, GBC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	64
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
155344	GRCh38/hg38 9p24.3-13.1(chr9:203861-38381642)	Pathogenic

SpliceAI

2802 predictions. Top by Δscore:

Variant	Effect	Δscore
9:15466739:ATT:A	donor_gain	1.0000
9:15466741:T:TA	donor_gain	1.0000
9:15466746:A:AC	donor_gain	1.0000
9:15466747:C:CC	donor_gain	1.0000
9:15466858:CCCT:C	acceptor_gain	1.0000
9:15466859:CCT:C	acceptor_gain	1.0000
9:15466861:T:C	acceptor_gain	1.0000
9:15468670:C:A	donor_gain	1.0000
9:15468695:T:TA	donor_gain	1.0000
9:15468843:TC:T	acceptor_loss	1.0000
9:15468844:CTG:C	acceptor_loss	1.0000
9:15468845:T:A	acceptor_loss	1.0000
9:15468951:ACTT:A	donor_loss	1.0000
9:15468953:TTACT:T	donor_loss	1.0000
9:15468954:TACTT:T	donor_loss	1.0000
9:15468955:A:AC	donor_gain	1.0000
9:15468955:ACTT:A	donor_loss	1.0000
9:15468956:C:A	donor_loss	1.0000
9:15468956:C:CG	donor_gain	1.0000
9:15468956:CT:C	donor_gain	1.0000
9:15468956:CTT:C	donor_gain	1.0000
9:15468956:CTTT:C	donor_gain	1.0000
9:15468956:CTTTT:C	donor_gain	1.0000
9:15469055:CATC:C	acceptor_gain	1.0000
9:15469057:TCCT:T	acceptor_loss	1.0000
9:15469058:CCT:C	acceptor_loss	1.0000
9:15469059:C:CC	acceptor_gain	1.0000
9:15469062:C:CT	acceptor_gain	1.0000
9:15469063:A:C	acceptor_gain	1.0000
9:15469067:C:CT	acceptor_gain	1.0000

AlphaMissense

3537 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:15468769:G:C	F427L	1.000
9:15468769:G:T	F427L	1.000
9:15468770:A:G	F427S	1.000
9:15468771:A:G	F427L	1.000
9:15468778:C:A	K424N	1.000
9:15468778:C:G	K424N	1.000
9:15468779:T:A	K424M	1.000
9:15468780:T:C	K424E	1.000
9:15468782:A:G	F423S	1.000
9:15468792:A:C	Y420D	1.000
9:15468792:A:G	Y420H	1.000
9:15468794:A:C	L419W	1.000
9:15468794:A:G	L419S	1.000
9:15468803:G:A	S416F	1.000
9:15468803:G:T	S416Y	1.000
9:15468804:A:G	S416P	1.000
9:15468805:C:A	K415N	1.000
9:15468805:C:G	K415N	1.000
9:15468807:T:C	K415E	1.000
9:15468815:A:C	I412S	1.000
9:15468815:A:T	I412N	1.000
9:15468816:T:A	I412F	1.000
9:15468823:A:C	S409R	1.000
9:15468823:A:T	S409R	1.000
9:15468825:T:G	S409R	1.000
9:15468832:G:C	F406L	1.000
9:15468832:G:T	F406L	1.000
9:15468833:A:G	F406S	1.000
9:15468834:A:G	F406L	1.000
9:15468834:A:T	F406I	1.000

dbSNP variants (sampled 300 via entrez): RS1000025824 (9:15504305 T>TTTAGTTA), RS1000043654 (9:15483945 T>A,C), RS1000094206 (9:15512533 C>G), RS1000103864 (9:15506893 G>A,C), RS1000292717 (9:15486581 C>G,T), RS1000302981 (9:15464403 A>G,T), RS1000342991 (9:15496553 C>T), RS1000442006 (9:15492270 G>C), RS1000444679 (9:15512302 C>T), RS1000472052 (9:15497985 A>C,G), RS1000552829 (9:15476763 A>G), RS1000596352 (9:15472930 G>T), RS1000598957 (9:15480410 G>A,C), RS1000626743 (9:15503370 A>G), RS1000696663 (9:15502307 C>A,T)

Disease associations

OMIM: gene MIM:603620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3988590 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 184,969 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3	NICOTINE	4	184,969

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

Binding affinities (BindingDB)

173 measured of 187 human assays (244 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-keto-4-(2-thienyl)butyric acid [2-(2-furfurylamino)-2-keto-ethyl] ester	EC50	1.74 nM
SMR000067268	IC50	408 nM
MLS000562014	IC50	408 nM
2-[2-methyl-4-(4-methylphenyl)-6,7,8,9-tetrahydrobenzo[g]quinolin-3-yl]pentanoic acid	IC50	470 nM	US-9132129: Antiviral compounds
2-[3-methyl-1-(4-methylphenyl)-7,8,9,10-tetrahydrobenzo[f]quinolin-2-yl]pentanoic acid	IC50	470 nM	US-9132129: Antiviral compounds
cid_67062	IC50	485 nM
cid_1912988	IC50	498 nM
L-DOPA	IC50	526 nM
2-[2-methyl-4-(4-methylphenyl)-6,7,8,9-tetrahydrobenzo[g]quinolin-3-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid	IC50	550 nM	US-9132129: Antiviral compounds
cid_56642849	IC50	1040 nM
2-[2-methyl-4-(4-methylphenyl)-7,8-dihydro-6H-cyclopenta[g]quinolin-3-yl]pentanoic acid	IC50	1080 nM	US-9132129: Antiviral compounds
2-[3-[2-hydroxyethyl(dimethyl)azaniumyl]propanoylamino]-2-methyl-propane-1-sulfonate	EC50	1160 nM
1-[[(E)-(2,3-dihydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]amino]-3-[3-(dimethylsulfamoyl)phenyl]thiourea	IC50	1170 nM
3-(2-{(E)-[1-(4-chlorophenyl)-2,5-dioxoimidazolidin-4-ylidene]methyl}-1H-pyrrol-1-yl)benzoic acid	IC50	1230 nM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-8-[(3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-2-oxanyl]-1-benzopyran-4-one	IC50	1260 nM
6-bromo-5,8-dihydroxy-7-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]naphthalene-1,4-dione;hydrochloride	IC50	1350 nM
5-(2-azanylethyl)benzene-1,2,4-triol;hydrobromide	IC50	1350 nM
MLS000876959	IC50	1550 nM
MLS000666608	IC50	1570 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
(2Z)-1,3-diketo-2-[(5-methyl-2-furyl)methylene]indane-5-carboxylic acid	IC50	1650 nM
(5Z)-5-[(E)-3-(2-furanyl)prop-2-enylidene]-3-(4-hydroxyphenyl)-2-sulfanylidene-4-thiazolidinone	IC50	1720 nM
mangiferin	IC50	1740 nM
(4E)-4-[[[4-(2-furanyl)-2-(2-methoxyethylimino)-3-thiazolyl]amino]methylidene]-2,3-dihydroxy-1-cyclohexa-2,5-dienone	EC50	1810 nM
3’,4’,5,7-tetrahydroxy-3-methoxyflavone	IC50	1900 nM
2,5-bis(2-furanylmethylidene)-1-cyclopentanone	IC50	1920 nM
[4-[(4-methylphenyl)diazenyl]-7-oxidanylidene-cyclohepta-1,3,5-trien-1-yl] 2-methylprop-2-enoate	IC50	1990 nM
MLS000736925	IC50	2070 nM
(E)-3-(5-methyl-2-furanyl)-N-[3-[[(E)-3-(5-methyl-2-furanyl)-1-oxoprop-2-enyl]amino]-4-nitrophenyl]-2-propenamide	IC50	2120 nM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	KI	2200 nM
4-[(3aR,4S,9bS)-8-[(4-methoxyphenyl)sulfamoyl]-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl]benzoic acid	EC50	2280 nM
(8S)-3-[3-[(2-methyl-1-oxoprop-2-enyl)amino]phenyl]-7-[(2E,4E)-1-oxohexa-2,4-dienyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	2300 nM
2-chloranyl-4-[5-[(Z)-2-[(5-methyl-1H-1,2,4-triazol-3-yl)sulfanyl]-3-oxidanyl-3-oxidanylidene-prop-1-enyl]furan-2-yl]benzoic acid	IC50	2350 nM
MLS000778637	IC50	2420 nM
2-(2-carbomethoxy-4-hydroxy-6-methoxy-phenoxy)-6-hydroxy-4-methyl-benzoic acid	IC50	2420 nM
(3Z)-3-(2-furanylmethylidene)-1,2-dihydrocyclopenta[b]quinoline-9-carboxylic acid [2-(cyclopentylamino)-2-oxoethyl] ester	IC50	2480 nM
2-[(6,7-dihydroxy-2-keto-chromen-4-yl)methylthio]-3-(3-methoxyphenyl)quinazolin-4-one	IC50	2720 nM
(4E)-2,3-dihydroxy-4-[[(4-methyl-2-methylimino-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	IC50	2720 nM
13,II8-biapigenin	IC50	2730 nM
cid_5831921	IC50	2830 nM
SMR001490544	IC50	2860 nM
1-(3,4-dihydroxyphenyl)-2-[(4-prop-2-enyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]ethanone	IC50	2920 nM
4-[(2-benzoxybenzyl)amino]phenol	EC50	2980 nM
(5E)-5-[(E)-3-(2-furanyl)prop-2-enylidene]-2-(4-methoxyanilino)-4-thiazolone	IC50	3020 nM
3-[2-(3-Cyano-7-hydroxy-5-oxo-4,5-dihydro-thieno[3,2-b]pyridin-2-ylsulfanyl)-acetylamino]-4-methyl-benzoic acid methyl ester	IC50	3040 nM
(8S)-3-(3-methacrylamidophenyl)-7-methacryloyl-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	3080 nM
SMR000528196	IC50	3090 nM
2-[2-methyl-4-(4-methylphenyl)pyrimido[1,2-b]indazol-3-yl]pentanoic acid	IC50	3100 nM	US-9132129: Antiviral compounds
2,3-bis(2-furanyl)-N-(3-hydroxypropyl)-6-quinoxalinecarboxamide	IC50	3450 nM
4-[[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxo-1,3-diazinan-5-ylidene]methyl]amino]benzamide	IC50	3450 nM

ChEMBL bioactivities

8 potent at pChembl≥5 of 19 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.33	IC50	470	nM	CHEMBL3981070
6.33	IC50	470	nM	CHEMBL3966037
6.26	IC50	550	nM	CHEMBL3964350
5.97	IC50	1080	nM	CHEMBL3979821
5.51	IC50	3100	nM	CHEMBL3910801
5.36	IC50	4400	nM	CHEMBL3979821
5.34	IC50	4600	nM	CHEMBL3941519
5.11	IC50	7850	nM	CHEMBL3910801

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
cobaltous chloride	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases phosphorylation, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
azoxystrobin	decreases expression	1
monomethylarsonous acid	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3887244	Binding	Alpha Screen Interaction Assay: An AlphaScreen assay was performed according to the manufacturer’s protocol (Perkin Elmer, Benelux). Reactions were performed in 25 ul final volume in 384-well Optiwell microtiter plates (Perkin Elmer). The r	Antiviral compounds

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3F4	Abcam HEK293T PSIP1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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