PSIP1

Chr 9

PC4 and SRSF1 interacting protein 1

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

NCBI Gene: 11168 ENSG00000164985 OMIM: 603620

PSIP1 encodes a transcriptional coactivator that regulates neuroepithelial stem cell differentiation and neurogenesis, and also functions in pre-mRNA splicing and lens development. Mutations cause autosomal dominant developmental delay with intellectual disability, seizures, and distinctive facial features, with onset in early childhood. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.27

Clinical Summary— PSIP1

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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.

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ClinVar Variants

60 VUS of 93 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

0.11Z-score

OE missense 0.98 (0.89–1.09)

262 obs / 266.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.06–0.27)

0≤0.351.4

Missense OE?0.98 (0.89–1.09)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 4 / 34.4Missense obs/exp: 262 / 266.9Syn Z: -2.26

This gene — mechanism propensity

0.2599th %ile

GOF

0.2298th %ile

LOF

0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign2

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	60	0	0	60
Likely Benign	1	0	1	2
Benign	2	1	1	4
Total	63	1	2	66

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

View in ClinVar →

103 pathogenic / likely-pathogenic (of 110) ClinVar copy-number / structural variants overlap PSIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →