RNU4-2

Chr 12ADAR

RNA, U4 small nuclear 2

Also known as: NEDHAFA, RENU, RNU4-1B, RNU4B1, RNU4C, RP102, U4A, U4b

NCBI Gene: 26834 ENSG00000202538 OMIM: 620823

This gene encodes U4 small nuclear RNA, a component of the spliceosome that binds U6 snRNA and is essential for pre-mRNA splicing through formation of the U4/U6 x U5 tri-snRNP complex. Mutations cause ReNU syndrome with autosomal dominant inheritance. The syndrome involves defects in RNA splicing that affect multiple organ systems during development.

OMIM ResearchSummary from RefSeq, OMIM

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

ReNU syndromeMIM #620851

Retinitis pigmentosa 102MIM #621560

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language · ADStrongappropriate for clinical testing

Interpreting a novel variant

Both loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Splicing / LOF*

Mechanism· annotated

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Mechanism of Pathogenicity

Splicing / LOFvariant-dependent

Non-coding U4 spliceosomal snRNA (not a protein — gene-level protein-mechanism predictors do not apply). De novo variants in the T-loop/Stem III critical region cause ReNU syndrome (autosomal dominant) by disrupting U4/U6 structure and 5' splice-site selection — an aberrant-splicing effect, not haploinsufficiency. Recently described biallelic variants outside the critical region cause a clinically distinct recessive disorder associated with reduced RNU4-2 expression (loss of function).

References: PMID 40297424, PMID 41951959

Expert-curated annotation. Non-coding RNA gene — protein-based mechanism predictors (Badonyi & Marsh) do not apply.