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…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

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Mechanism

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GeneReview available — RNU4-1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in RNU4-1?

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 RNU4-1; 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.