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. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Splicing / LOFmechanismAD/AR2 OMIM phenotypes

Clinical Summary— RNU4-2

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Gene-Disease Validity (ClinGen)

neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language · ADStrong

Strong evidence — appropriate for clinical testing

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ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 33 VUS of 86 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RNU4-2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

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.

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic23

VUS33

Likely Benign17

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	11	0	11
Likely Pathogenic	0	0	23	0	23
VUS	0	0	33	0	33
Likely Benign	0	0	17	0	17
Benign	0	0	0	0	0
Conflicting	—				2
Total	0	0	84	0	86

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

View in ClinVar →

4 pathogenic / likely-pathogenic (of 5) ClinVar copy-number / structural variants overlap RNU4-2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →