HNRNPU

Chr 1AD

heterogeneous nuclear ribonucleoprotein U

Also known as: DEE54, EIEE54, GRIP120, HNRNPU-AS1, HNRPU, SAF-A, SAFA, U21.1

NCBI Gene: 3192ENSG00000153187UniProt: Q00839OMIM: 602869

The protein binds heterogeneous nuclear RNA and scaffold-attached region DNA to form ribonucleoprotein complexes in the nucleus. Loss-of-function mutations cause developmental and epileptic encephalopathy 54 through autosomal dominant inheritance. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.111 OMIM phenotype
Clinical Summary— HNRNPU
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · 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
85 unique Pathogenic / Likely Pathogenic· 171 VUS of 500 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — HNRNPU
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 5.84
OE 0.02 (0.01–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.37Z-score
OE missense 0.56 (0.50–0.62)
253 obs / 455.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.11)
0≤0.351.4
Missense OE0.56 (0.50–0.62)
0≤0.61.4
Synonymous OE1.28
0≤1.21.6
LoF obs/exp: 1 / 41.7Missense obs/exp: 253 / 455.5Syn Z: -2.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHNRNPU-related epileptic encephalopathyLOFAD
DN
0.16100th %ile
GOF
0.2597th %ile
LOF
0.84top 5%

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

LOFprediction above median · 1 literature citation · 56% of P/LP variants are LoF · LOEUF 0.11

Literature Evidence

LOFUnique and variable clinical features are related to loss-of-function or haploinsufficiency of HNRNPU.PMID:29858110

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

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic24
VUS171
Likely Benign189
Benign12
Conflicting12
61
Pathogenic
24
Likely Pathogenic
171
VUS
189
Likely Benign
12
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
2
26
0
61
Likely Pathogenic
15
2
7
0
24
VUS
4
153
12
2
171
Likely Benign
0
27
63
99
189
Benign
0
8
3
1
12
Conflicting
—12
Total52192111102469

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

View in ClinVar →

Protein Context — Lollipop Plot

HNRNPU · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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