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.

GeneReviews 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. Implicated in ReNU syndrome. [provided by Alliance of Genome Resources, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

ReNU syndromeMIM #620851

Retinitis pigmentosa 102MIM #621560

Clinical highlights

Gene–disease validity (ClinGen)

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)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Splicing / LOF*

Mechanism· annotated

📖

GeneReview available — RNU4-2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

ReNU syndrome & the snRNA disorders — features, recurrent variants, where they sit, testing and counsellingOverview →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in RNU4-2?

gnomAD v4 · ~0k individuals · PASS only

Rare means allele frequency under

Rare missense

none observed

0 rare PASS variants

Rare truncating (LoF)

none observed

0 rare PASS variants

Rare synonymous (reference)

none observed

0 rare PASS variants

Rare missense and truncating variants are carried at similar rates in RNU4-2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

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.