RNU4-1

Chr 12

RNA, U4 small nuclear 1

Also known as: RNU4A, RNU4B2, U4, U4BL

NCBI Gene: 26835 ENSG00000200795 OMIM: 620822

This gene encodes U4 small nuclear RNA, a key component of the spliceosome that binds U6 snRNA and participates in the assembly of the U4/U6 x U5 tri-snRNP complex required for pre-mRNA splicing. Mutations cause microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR), an autosomal recessive disorder characterized by severe intellectual disability, microcephaly, and variable features including retinal dystrophy and lymphedema with onset in infancy. This represents one of the few known human diseases caused by defects in core spliceosomal machinery.

GeneReviews OMIM ResearchSummary from RefSeq

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…

Clinical Summary— RNU4-1

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 1 VUS of 2 total submissions

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GeneReview available — RNU4-1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

2 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS1

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Non-coding	Total
Pathogenic	1	1
Likely Pathogenic	0	0
VUS	1	1
Likely Benign	0	0
Benign	0	0
Total	2	2

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

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4 pathogenic / likely-pathogenic (of 5) ClinVar copy-number / structural variants overlap RNU4-1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →