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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 98 total — 1 pathogenic
• GTEx eGene: eQTL in 14 tissues, sQTL in 4 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.40 (moderately constrained)
• MANE Select transcript: NM_033222
• Notable: 98 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 51 — 39 protein_coding, 7 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000380733

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 3, TSL 3: 2, TSL 5: 2

ENST00000380733, ENST00000380715, ENST00000380716, ENST00000380738, ENST00000397519, ENST00000463712, ENST00000481862, ENST00000484265, ENST00000487363, ENST00000488797, ENST00000495873, ENST00000901729, ENST00000901730, ENST00000901731, ENST00000901732, ENST00000901733, ENST00000917556, ENST00000917557, ENST00000917558, ENST00000917559, ENST00000917560, ENST00000917561, ENST00000950211, ENST00000950212, ENST00000950213, ENST00000950214, ENST00000950215, ENST00000981926, ENST00000981927, ENST00000981928, ENST00000981929, ENST00000981930, ENST00000981931, ENST00000981932, ENST00000981933, ENST00001014589, ENST00001014591, ENST00001014592, ENST00001014593, ENST00001014594, ENST00001083420, ENST00001083421, ENST00001083422, ENST00001083423, ENST00001083424, ENST00001083425, ENST00001083426, ENST00001083432, ENST00001083433, ENST00001114373, ENST00001138052

RefSeq mRNA: 12 — MANE Select: NM_033222 NM_001128217, NM_001317898, NM_001317900, NM_001438383, NM_001438384, NM_001438385, NM_001438386, NM_001438387, NM_001438388, NM_001438389, 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.

Highest expression (Bgee): secondary oocyte, ventricular zone, ganglionic eminence, cortical plate, cerebellar hemisphere.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSIP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Muscularis	eqtl	1.3e-22	-0.28	9:15469735:T:G
Esophagus Gastroesophageal Junction	eqtl	3.7e-21	-0.28	9:15469735:T:G
Testis	sqtl	3.8e-08	-0.72	9:15466035:G:C
Cells EBV-transformed lymphocytes	eqtl	5.1e-08	+0.32	9:15511407:T:TC
Whole Blood	eqtl	3.3e-04	-0.17	9:15507682:AT:A
Breast Mammary Tissue	sqtl	1.8e-03	-1.18	9:16309276:A:G
Colon Sigmoid	eqtl	4.0e-03	+0.23	9:15429856:A:G
Artery Aorta	eqtl	4.5e-03	+0.16	9:15504354:T:TA
Brain Cerebellum	eqtl	5.0e-03	-0.71	9:15145425:T:C
Brain Frontal Cortex BA9	eqtl	9.7e-03	+0.93	9:15425452:A:G
Artery Tibial	eqtl	1.2e-02	+0.18	9:15509965:T:C
Cells Cultured fibroblasts	sqtl	1.4e-02	+0.33	9:15519813:T:G
Skin Not Sun Exposed Suprapubic	eqtl	1.5e-02	+0.17	9:15509965:T:C
Thyroid	eqtl	1.8e-02	+0.13	9:14838914:G:A
Brain Caudate basal ganglia	eqtl	1.9e-02	+0.73	9:15351452:A:G
Cells EBV-transformed lymphocytes	sqtl	2.2e-02	-0.53	9:15460476:C:T
Skin Sun Exposed Lower leg	eqtl	3.1e-02	+0.16	9:15431843:A:C
Adipose Subcutaneous	eqtl	4.5e-02	+0.10	9:15479952:A:G

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

showing 100 of 295 tissues 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
anterior cingulate cortex	UBERON:0009835	96.46	gold quality
central nervous system	UBERON:0001017	96.43	gold quality
left ovary	UBERON:0002119	96.42	gold quality
brain	UBERON:0000955	96.41	gold quality
germinal epithelium of ovary	UBERON:0001304	96.41	gold quality
right ovary	UBERON:0002118	96.41	gold quality
telencephalon	UBERON:0001893	96.38	gold quality
forebrain	UBERON:0001890	96.33	gold quality
neocortex	UBERON:0001950	96.29	gold quality
cerebral cortex	UBERON:0000956	96.24	gold quality
pigmented layer of retina	UBERON:0001782	96.23	gold quality
frontal cortex	UBERON:0001870	96.18	gold quality
seminal vesicle	UBERON:0000998	96.05	gold quality
parietal pleura	UBERON:0002400	96.05	gold quality
choroid plexus epithelium	UBERON:0003911	96.05	gold quality
adenohypophysis	UBERON:0002196	95.95	gold quality
Ammon’s horn	UBERON:0001954	95.94	gold quality
left testis	UBERON:0004533	95.85	gold quality
right testis	UBERON:0004534	95.84	gold quality
lymph node	UBERON:0000029	95.83	gold quality
pituitary gland	UBERON:0000007	95.78	gold quality
bronchial epithelial cell	CL:0002328	95.77	gold quality
testis	UBERON:0000473	95.75	gold quality
thoracic aorta	UBERON:0001515	95.71	gold quality
corpus callosum	UBERON:0002336	95.71	gold quality
superficial temporal artery	UBERON:0001614	95.66	gold quality
ascending aorta	UBERON:0001496	95.64	gold quality
temporal lobe	UBERON:0001871	95.57	gold quality
endocervix	UBERON:0000458	95.56	gold quality
trabecular bone tissue	UBERON:0002483	95.50	gold quality
aorta	UBERON:0000947	95.45	gold quality
vermiform appendix	UBERON:0001154	95.34	gold quality
cauda epididymis	UBERON:0004360	95.29	gold quality
pons	UBERON:0000988	95.28	gold quality
tibial nerve	UBERON:0001323	95.27	gold quality
popliteal artery	UBERON:0002250	95.26	gold quality
tibial artery	UBERON:0007610	95.26	gold quality
substantia nigra	UBERON:0002038	95.19	gold quality
body of uterus	UBERON:0009853	95.19	gold quality
pleura	UBERON:0000977	95.16	gold quality
right uterine tube	UBERON:0001302	95.13	gold quality
tendon	UBERON:0000043	95.02	gold quality
periodontal ligament	UBERON:0008266	95.02	gold quality
skin of hip	UBERON:0001554	95.00	gold quality
cerebellar vermis	UBERON:0004720	94.91	gold quality
midbrain	UBERON:0001891	94.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.78	gold quality
right coronary artery	UBERON:0001625	94.76	gold quality
colonic epithelium	UBERON:0000397	94.71	gold quality
caecum	UBERON:0001153	94.63	gold quality
primary visual cortex	UBERON:0002436	94.54	gold quality
thymus	UBERON:0002370	94.40	gold quality
lateral globus pallidus	UBERON:0002476	94.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.40	gold quality
rectum	UBERON:0001052	94.38	gold quality
left uterine tube	UBERON:0001303	94.31	gold quality
gall bladder	UBERON:0002110	94.28	gold quality
left coronary artery	UBERON:0001626	94.25	gold quality
paraflocculus	UBERON:0005351	94.18	gold quality
adrenal tissue	UBERON:0018303	94.11	gold quality
caput epididymis	UBERON:0004358	94.08	gold quality
coronary artery	UBERON:0001621	93.91	gold quality
ectocervix	UBERON:0012249	93.90	gold quality
endometrium	UBERON:0001295	93.86	gold quality
myometrium	UBERON:0001296	93.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.79	gold quality
tibia	UBERON:0000979	93.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.73	gold quality
female reproductive system	UBERON:0000474	93.72	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	236.4	high
Olfactory bulb	tissue	204.9
Prefrontal cortex	tissue	199.2
Cerebral cortex	tissue	199.2	high
Occipital cortex	tissue	189.4
Hippocampal formation	tissue	188.2
Putamen	tissue	187.3
Septum	tissue	186.8
Basal ganglia	tissue	183.5	high
Ventral forebrain	tissue	181.0
Motor cortex	tissue	171.2
Thalamus	tissue	171.1
Entorhinal cortex	tissue	170.6
Somatosensory cortex	tissue	167.5
Temporal cortex	tissue	167.1
Midbrain	tissue	161.8
Retrosplenial and cingulate cortex	tissue	160.7
Corpus callosum	tissue	157.7
Pons	tissue	149.0
Retrosplenial cortex	tissue	147.8
Amygdala	tissue	147.3
Insular cortex	tissue	146.4
Hypothalamus	tissue	145.4
Periaqueductal gray	tissue	144.2
Retina	tissue	143.4
Superior colliculi	tissue	141.4
Medulla oblongata	tissue	137.6
Substantia nigra	tissue	129.9
Caudate putamen	tissue	129.5
Spinal cord	tissue	126.2
Thymus	tissue	120.9
Frontal cortex	tissue	118.2
Postcentral gyrus	tissue	116.2
Nucleus accumbens	tissue	90.8
Hippocampus	tissue	80.1	high
Locus coeruleus	tissue	79.3
Testis	tissue	76.4	high
Lymph node	tissue	76.0	high
Ovary	tissue	74.7	high
Tonsil	tissue	65.0	high
Choroid plexus	tissue	62.0
Bone marrow	tissue	58.5	medium
Endometrium 1	tissue	54.1	high
Spleen	tissue	51.8	high
Pituitary gland	tissue	48.8
Appendix	tissue	44.5	high
Smooth muscle	tissue	40.4	medium
Adrenal gland	tissue	38.9	medium
Seminal vesicle	tissue	38.7	medium
Placenta	tissue	37.3	high
Fallopian tube	tissue	37.3	medium
Skeletal muscle	tissue	36.2	medium
Thyroid gland	tissue	35.1	medium
Prostate	tissue	34.2	medium
Epididymis	tissue	33.9	medium
Cervix	tissue	33.4	medium
Heart muscle	tissue	32.5	medium
Lung	tissue	31.1	high
Adipose tissue	tissue	30.9	medium
Vagina	tissue	30.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal hippocampus (188.2), Subiculum (184.8), Ventral hippocampus (165.3), White matter (157.7), Orbitofrontal gyrus, anterior (134.8).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting PSIP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 136 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.397, missense Z 0.415 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000380733 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:15,465,523–15,490,009	538 / 507.6	1.06	no
9:15,490,010–15,510,188	63 / 106.7	0.59	no

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

3 orthologs

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

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2142116) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 51 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal abdominal fat pad morphology	1
abnormal neurocranium morphology	1
abnormal nasal bone morphology	1
abnormal vertebrae morphology	1
abnormal rib morphology	1
asymmetric rib joints	1
broad head	1
shortened head	1
abnormal cranium morphology	1
domed cranium	1
abnormal jaw morphology	1
small testis	1
decreased locomotor activity	1
hunched posture	1
limb grasping	1
reduced male fertility	1
abnormal axial skeleton morphology	1
decreased vertical activity	1
abnormal rib development	1
vertebral transformation	1
abnormal cervical vertebrae morphology	1
decreased rib number	1
spleen atrophy	1
embryonic growth retardation	1
abnormal spine curvature	1

+26 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R7T2	99.5%	Diamond
Bos taurus	A4FUF0	98.4%	Diamond
Gallus gallus	Q5ZLS7	96.6%	Diamond
Felis catus	Q66T72	94.7%	Diamond
Xenopus tropicalis	Q6P4K1	84.4%	Diamond
Xenopus laevis	Q32N87	84.3%	Diamond
Drosophila pseudoobscura pseudoobscura	Q29NG1	82.7%	Diamond
Drosophila melanogaster	Q8T079	81.9%	Diamond
Aedes aegypti	Q175F8	74.6%	Diamond
Anopheles gambiae	Q7Q161	74.6%	Diamond
Arabidopsis thaliana	F4IZM8	60.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNAPC3	protein-coding	6619
TTC39B	protein-coding	158219

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 (12): NP_001121689, NP_001304827, NP_001304829, NP_001425312, NP_001425313, NP_001425314, NP_001425315, NP_001425316, NP_001425317, NP_001425318, 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 (82 total): modified residue 21, helix 14, 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)

showing 30 of 40 structures by resolution:

PDB	Title	Method	Resolution (Å)
6TRJ	LEDGF/p75 IBD dimer	X-RAY DIFFRACTION	1.3
9S81	Crystal structure of the LEDGF PWWP domain	X-RAY DIFFRACTION	1.63
5N88	Crystal structure of antibody bound to viral protein	X-RAY DIFFRACTION	1.7
2B4J	Structural basis for the recognition between HIV-1 integrase and LEDGF/p75	X-RAY DIFFRACTION	2.02
5OYM	HIV Integrase Binding Domain of Lens Epithelium-Derived Growth Factor	X-RAY DIFFRACTION	2.05
4FU6	Crystal structure of the PSIP1 PWWP domain	X-RAY DIFFRACTION	2.1
9S83	Crystal structure of de novo designed binder JUBO4 and the LEDGF PWWP domain	X-RAY DIFFRACTION	2.1
3HPH	Closed tetramer of Visna virus integrase (residues 1-219) in complex with LEDGF IBD	X-RAY DIFFRACTION	2.64
8PEO	H3K36me2 nucleosome-LEDGF/p75 PWWP domain complex	ELECTRON MICROSCOPY	2.69
9S28	MVV STC intasome in complex with LEDGF	ELECTRON MICROSCOPY	2.8
9S29	MVV CSC intasome in complex with LEDGF	ELECTRON MICROSCOPY	2.8
3U88	Crystal structure of human menin in complex with MLL1 and LEDGF	X-RAY DIFFRACTION	3
7OUF	Structure of the STLV intasome:B56 complex bound to the strand-transfer inhibitor XZ450	ELECTRON MICROSCOPY	3
8PC5	H3K36me3 nucleosome-LEDGF/p75 PWWP domain complex	ELECTRON MICROSCOPY	3.02
8PC6	H3K36me3 nucleosome-LEDGF/p75 PWWP domain complex - pose 2	ELECTRON MICROSCOPY	3.04
7OUG	STLV-1 intasome:B56 in complex with the strand-transfer inhibitor raltegravir	ELECTRON MICROSCOPY	3.1
3F9K	Two domain fragment of HIV-2 integrase in complex with LEDGF IBD	X-RAY DIFFRACTION	3.2
6S01	Structure of LEDGF PWWP domain bound H3K36 methylated nucleosome	ELECTRON MICROSCOPY	3.2
3HPG	Visna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open …	X-RAY DIFFRACTION	3.28
8PEP	H3K36me2 nucleosome-LEDGF/p75 PWWP domain complex - pose 2	ELECTRON MICROSCOPY	3.33
7PEL	CryoEM structure of simian T-cell lymphotropic virus intasome in complex with PP2A …	ELECTRON MICROSCOPY	3.34
8CBN	structure of LEDGF/p75 PWWP domain bound to the H3K36 trimethylated dinucleosome	ELECTRON MICROSCOPY	3.34
7OUH	Structure of the STLV intasome:B56 complex bound to the strand-transfer inhibitor …	ELECTRON MICROSCOPY	3.5
7Z1Z	MVV strand transfer complex (STC) intasome in complex with LEDGF/p75 at 3.5 A resolution	ELECTRON MICROSCOPY	3.5
9XYC	Pol II-DSIF-SPT6-PAF1c-TFIIS-IWS1-ELOF1-LEDGF-nucleosome LEDGF+nucleosome map Q	ELECTRON MICROSCOPY	3.5
8CBQ	structure of LEDGF/p75 PWWP domain bound to the H3K36 trimethylated dinucleosome	ELECTRON MICROSCOPY	4
9BW9	Tetrameric Complex of full-length HIV-1 integrase protein bound to the integrase binding …	ELECTRON MICROSCOPY	4.1
1Z9E	Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75	SOLUTION NMR
2M16	P75/LEDGF PWWP Domain	SOLUTION NMR
2MSR	Solution structure of LEDGF/p75 IBD in complex with MLL1 peptide (140-160)	SOLUTION NMR

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 5N88

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF enhanced

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)

Type	Positions
Phosphoserine	102, 105, 106, 129, 177, 206, 271, 273, 275, 434, 443, 514, 522
Phosphothreonine	115, 122, 141, 167, 272, 437, 527
Citrulline	517
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	75

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 curated (TAS) of 18; 14 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

18 pathways:

ID	Pathway	Evidence
R-HSA-164843	2-LTR circle formation ⚕	curated
R-HSA-180689	APOBEC3G mediated resistance to HIV-1 infection ⚕	curated
R-HSA-177539	Autointegration results in viral DNA circles ⚕	curated
R-HSA-162592	Integration of provirus ⚕	curated
R-HSA-175567	Integration of viral DNA into host genomic DNA ⚕	curated
R-HSA-180910	Vpr-mediated nuclear import of PICs ⚕	curated
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-162594	Early Phase of HIV Life Cycle ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162587	HIV Life Cycle ⚕	—
R-HSA-162909	Host Interactions of HIV factors ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-176033	Interactions of Vpr with host cellular proteins ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-74160	Gene expression (Transcription)	—

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 (6): mRNA 5’-splice site recognition (GO:0000395), chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), 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

12 top-level categories:

Category	Pathways
Integration of provirus	3
Host Interactions of HIV factors	2
HIV Infection	2
Early Phase of HIV Life Cycle	1
Interactions of Vpr with host cellular proteins	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
HIV Life Cycle	1
Viral Infection Pathways	1
Gene expression (Transcription)	1
Disease	1
Infectious disease	1
Epigenetic regulation of gene expression	1

GO top-level categories

20 GO namespaces:

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
gene expression	1
RNA biosynthetic process	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
mRNA 5’-splice site recognition	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
heterochromatin	CC	direct assay
nuclear periphery	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
DNA-binding transcription factor binding	MF	direct assay
RNA binding	MF	high-throughput assay
chromatin binding	MF	direct assay
transcription coactivator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,552 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSIP1	DDX10	Q13206	722
PSIP1	NSD1	Q96L73	710
PSIP1	NUP98	P52948	693
PSIP1	CDCA7L	Q96GN5	678
PSIP1	HOXA9	P31269	672
PSIP1	TNPO3	Q9Y5L0	664
PSIP1	NSD3	Q9BZ95	663
PSIP1	MEN1	O00255	663
PSIP1	RAP1GDS1	P52306	663
PSIP1	PHF23	Q9BUL5	660
PSIP1	CPSF6	Q16630	643
PSIP1	SRSF1	Q07955	613
PSIP1	SETBP1	Q9Y6X0	601
PSIP1	HOXC13	P31276	590
PSIP1	NUP153	P49790	587

IntAct

Human interaction partners of PSIP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
RBBP8	physical association	0.600	4
SUMO1	association	0.430	4
GDF5	physical association	0.400	1
HSPA8	physical association	0.400	1
IGHMBP2	physical association	0.400	1
PPP1R13B	physical association	0.400	1
SCAF11	physical association	0.400	1
TMEM214	physical association	0.400	1
MAPK6	physical association	0.370	1
MEN1	association	0.350	1
VIM	association	0.350	1

BioGRID (289 interactions; top human partners by supporting records): HIST1H3A (Protein-peptide; 8 records), MEN1 (Affinity Capture-MS; 5 records), BRD4 (Affinity Capture-MS; 4 records), HDGF (Cross-Linking-MS (XL-MS); 4 records), KMT2A (Affinity Capture-MS; 4 records), CDCA7L (Affinity Capture-Western; 3 records), HDGFRP2 (Affinity Capture-MS; 3 records), HMGA1 (Affinity Capture-MS; 3 records), HMGA2 (Proximity Label-MS; 3 records), SRSF1 (Far Western; 3 records), SUMO1 (Affinity Capture-Western; 3 records), WDR5 (Affinity Capture-MS; 3 records), ASH2L (Affinity Capture-MS; 2 records), FOXA1 (Affinity Capture-MS; 2 records), H3F3A (Proximity Label-MS; 2 records)

SIGNOR signaling

3 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
MLL2 complex	10	DPY30, HCFC2, KMT2D, MEN1, PSIP1, ASH2L, HCFC1, OGT, RBBP5, WDR5

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for PSIP1: 98 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

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)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
155344	GRCh38/hg38 9p24.3-13.1(chr9:203861-38381642)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PSIP1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 1,510):

Position(s)	Effect	Δscore	Sites
9:15466861	acceptor_gain	1.0000
9:15468670	donor_gain	1.0000
9:15468845	acceptor_loss	1.0000
9:15468955–15468956	donor_loss	1.0000	5
9:15469059	acceptor_loss	1.0000
9:15469063	acceptor_gain	1.0000
9:15469337–15469338	acceptor_loss	1.0000	5
9:15469344	acceptor_gain	1.0000
9:15472630–15472631	donor_loss	1.0000	3
9:15472751–15472752	acceptor_loss	1.0000	5

AlphaMissense

1,364 missense substitutions predicted likely pathogenic (of 3,537 scored), across 275 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M15	9	0.996	1.000
M418	9	0.912	0.994
M426	9	0.896	0.989
F44	8	0.999	1.000
F12	8	0.998	1.000
D57	8	0.998	1.000
F77	8	0.998	1.000
H48	8	0.996	1.000
F43	8	0.989	1.000
H356	8	0.989	0.999
F427	8	0.988	1.000
F52	8	0.987	1.000
H20	8	0.985	1.000
D9	8	0.981	0.999
F406	8	0.977	1.000
F45	8	0.975	1.000
D26	8	0.974	0.996
F423	8	0.974	1.000
D369	8	0.970	0.996
H393	8	0.969	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000142

Disease associations

OMIM: gene MIM:603620 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3988590 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 187,543 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3	NICOTINE	4	187,543

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

189 measured of 205 human assays (264 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
cid_10414856	IC50	80 nM
Methylene Blue anhydrous	KI	110 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
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
MLS000578867	EC50	830 nM
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
MLS000776241	IC50	1170 nM
cid_16745469	EC50	1240 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
CHEMBL5653589	KD	1440 nM
MLS000876959	IC50	1550 nM
cid_1231130	IC50	1550 nM
MLS000666608	IC50	1570 nM
cid_2258593	IC50	1600 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
5-(2-aminoethyl)benzene-1,2,4-triol;hydrobromide	IC50	1610 nM
SMR000390645	EC50	1690 nM
mangiferin	IC50	1740 nM
cid_6040412	EC50	1810 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
MLS000553820	IC50	2190 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
(8R)-3-[3-[(2-methyl-1-oxoprop-2-enyl)amino]phenyl]-7-[(E)-1-oxobut-2-enyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	EC50	2710 nM
2-[(6,7-dihydroxy-2-keto-chromen-4-yl)methylthio]-3-(3-methoxyphenyl)quinazolin-4-one	IC50	2720 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
2-(4-hydroxyphenyl)-5,6,7,8-tetrakis(oxidanyl)chromen-4-one	IC50	2970 nM
4-[(2-benzoxybenzyl)amino]phenol	EC50	2980 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
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-(2,3-Dimethyl-phenylamino)-5-[(E)-3-furan-2-yl-prop-2-en-(Z)-ylidene]-thiazol-4-one	EC50	3170 nM
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
SMR000369439	IC50	3520 nM
5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[[3,4,5-trihydroxy-6-[(3,4,5-trihydroxy-6-methyl-2-oxanyl)oxymethyl]-2-oxanyl]oxy]-1-benzopyran-4-one	IC50	3570 nM
MLS000049147	IC50	3570 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	decreases expression, increases expression, affects 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	affects methylation, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PSIP1 across ~30M SureChEMBL compounds — explore on Sugi Predict.