PUF60

Chr 8AD

poly(U) binding splicing factor 60

Also known as: FIR, RoBPI, SIAHBP1, VRJS

NCBI Gene: 22827ENSG00000179950UniProt: Q9UHX1OMIM: 604819

The protein encoded by this gene is a DNA- and RNA-binding protein that regulates pre-mRNA splicing, transcription (including MYC repression), and apoptosis. Mutations cause Verheij syndrome, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.245), indicating that such mutations are likely to have significant clinical consequences.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.241 OMIM phenotype
Clinical Summary— PUF60
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
171 unique Pathogenic / Likely Pathogenic· 115 VUS of 362 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.24LOEUF
pLI 0.997
Z-score 4.33
OE 0.08 (0.03–0.24)
Highly constrained

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

Missense Constraint
4.44Z-score
OE missense 0.32 (0.28–0.38)
111 obs / 341.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.03–0.24)
0≤0.351.4
Missense OE0.32 (0.28–0.38)
0≤0.61.4
Synonymous OE1.24
0≤1.21.6
LoF obs/exp: 2 / 25.7Missense obs/exp: 111 / 341.8Syn Z: -2.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePUF60-related Verheij syndromeLOFAD
DN
0.3296th %ile
GOF
0.4480th %ile
LOF
0.78top 5%

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

LOFprediction above median · 1 literature citation · 49% of P/LP variants are LoF · LOEUF 0.24

Literature Evidence

LOFThe distribution of the heterozygous de novo variants (DNV) is shown in context of the genomic structure of PUF60 in Figure 1. Nine of the DNV were predicted to cause loss-of function suggesting haploinsufficiency as the likely mutational mechanism.PMID:28327570

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

362 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic110
Likely Pathogenic61
VUS115
Likely Benign45
Benign6
Conflicting6
110
Pathogenic
61
Likely Pathogenic
115
VUS
45
Likely Benign
6
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
47
3
60
0
110
Likely Pathogenic
37
19
5
0
61
VUS
8
93
13
1
115
Likely Benign
0
10
6
29
45
Benign
0
0
4
2
6
Conflicting
—6
Total921258832343

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

View in ClinVar →

Protein Context — Lollipop Plot

PUF60 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients