PSIP1

Chr 9

PC4 and SRSF1 interacting protein 1

Also known as: DFS70, LEDGF, PAIP, PSIP2, p52, p75

NCBI Gene: 11168ENSG00000164985UniProt: O75475

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. [provided by Alliance of Genome Resources, Jul 2025]

201
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PSIP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 62 VUS of 201 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.27LOEUF
pLI 0.997
Z-score 4.81
OE 0.12 (0.06–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.11Z-score
OE missense 0.98 (0.89–1.09)
262 obs / 266.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.06–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.31
0≤1.21.6
LoF obs/exp: 4 / 34.4Missense obs/exp: 262 / 266.9Syn Z: -2.26

ClinVar Variant Classifications

201 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS62
9
Pathogenic
3
Likely Pathogenic
62
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
3
0
3
VUS
0
59
3
0
62
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total05915074

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PSIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A preliminary bioinformatic screen to identify SRI SMC2 PSIP1 TLE4 and MSX1 as potential diagnostic and prognostic markers of osteoarthritis.
Kryczka J et al.·Sci Rep
2025
Ese-3 Inhibits the Proliferation, Migration, and Invasion of HaCaT Cells by Downregulating PSIP1 and NUCKS1.
Zhang C et al.·Ann Clin Lab Sci
2021
Deciphering Immune Endotypes Within Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome.
von Wachter C et al.·Allergy
2025
Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells.
Sanchez-Hernandez ES et al.·Cells
2023
Alternative Splicing in Glioblastoma and its Clinical Implication in Outcome Prediction.
Zheng P et al.·Neurol India
2024
The LncRNA MIR155HG is Upregulated by SP1 in Melanoma Cells and Drives Melanoma Progression via Modulating the MiR-485-3p/PSIP1 Axis.
Huo J et al.·Anticancer Agents Med Chem
2022
Identification of an individualized RNA binding protein-based prognostic signature for diffuse large B-cell lymphoma.
Xie Y et al.·Cancer Med
2021
Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.
Kiselinova M et al.·PLoS Pathog
2016
Oncogenic states dictate the prognostic and predictive connotations of intratumoral immune response.
Roelands J et al.·J Immunother Cancer
2020
PSIP1/LEDGF: a new gene likely involved in sensorineural progressive hearing loss.
Girotto G et al.·Sci Rep
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools