RNU4-2

Chr 12AD

RNA, U4 small nuclear 2

Also known as: NEDHAFA, RENU, RNU4-1B, RNU4B1, RNU4C, U4A, U4b, U4c

NCBI Gene: 26834ENSG00000202538

Predicted to enable U6 snRNA binding activity. Predicted to be involved in formation of quadruple SL/U4/U5/U6 snRNP and spliceosomal tri-snRNP complex assembly. Predicted to be part of U4 snRNP and U4/U6 x U5 tri-snRNP complex. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

ReNU syndromeMIM #620851
AD
83
ClinVar variants
36
Pathogenic / LP
—
pLI score
1
Active trials
Clinical Summary— RNU4-2
🧬
Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language · ADStrong

Strong evidence — appropriate for clinical testing

📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 35 VUS of 83 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic23
VUS35
Likely Benign12
13
Pathogenic
23
Likely Pathogenic
35
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
23
0
23
VUS
0
0
35
0
35
Likely Benign
0
0
12
0
12
Benign
0
0
0
0
0
Total0083083

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

View in ClinVar →

Protein Context — Lollipop Plot

RNU4-2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RNU4-2-related neurodevelopmental disorder with microcephaly and seizures (ReNU syndrome)

strong
ADLoss Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
non coding transcript variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

ReNU syndrome

MIM #620851

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome.
Valenzuela I et al.·Genet Med
2024
The Face and Features of RNU4-2: A New, Common, Recognizable, Yet Hidden Neurodevelopmental Disorder.
Barbour K et al.·Pediatr Neurol
2024
Genotype-phenotype correlations and phenotypic expansion in a case series of ReNU syndrome associated with RNU4-2 variants.
Kuroda Y et al.·J Med Genet
2025Cohort
Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption.
Nava C et al.·Nat Genet
2025
Expanding the mutational spectrum of ReNU syndrome: insights into 5' Stem-loop variants.
Bruselles A et al.·Eur J Hum Genet
2025
Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy.
Greene D et al.·Nat Genet
2025
Identification of a pathogenic RNU4-2 variant in patients with mitochondrial disease: Broadening the spectrum of non-coding RNA gene variants in mitochondrial dysfunction.
Nakamura K et al.·J Hum Genet
2025Case report
RNU4-2 monoallelic variants as a leading cause of syndromic neurodevelopmental disorder, including in patients with parental consanguinity.
Bertoli-Avella AM et al.·J Med Genet
2025Cohort
RNU4-2-Related Neurodevelopmental Disorder Is Associated With a Recognisable Facial Gestalt.
Rosenblum J et al.·Clin Genet
2025Case report
A Clinical Study of Nine Patients With ReNU Syndrome.
Okamoto N et al.·Am J Med Genet A
2025Cohort
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
Rare DiseasesAlbinismIntellectual Disability

Implementation of Long-read Sequencing for the Diagnosis of Rare Diseases.

NOT YET RECRUITING
NCT07400913University Hospital, BordeauxStarted 2026-02
Long-read sequencing

External Resources

Links to major genomics databases and tools