RNU4ATAC

Chr 2AR

RNA, U4atac small nuclear

Also known as: LWS, MOPD1, RFMN, RNU4ATAC1, TALS, U4ATAC

NCBI Gene: 100151683ENSG00000264229

The small nuclear RNA (snRNA) encoded by this gene is part of the U12-dependent minor spliceosome complex. In addition to the encoded RNA, this ribonucleoprotein complex consists of U11, U12, U5, and U6atac snRNAs. The U12-dependent spliceosome acts on approximately 700 specific introns in the human genome. Defects in this gene are a cause of microcephalic osteodysplastic primordial dwarfism type 1 (MOPD). [provided by RefSeq, Jul 2011]

Primary Disease Associations & Inheritance

Lowry-Wood syndromeMIM #226960
AR
Microcephalic osteodysplastic primordial dwarfism, type IMIM #210710
AR
Roifman syndromeMIM #616651
AR
283
ClinVar variants
55
Pathogenic / LP
—
pLI score
2
Active trials
Clinical Summary— RNU4ATAC
🧬
Gene-Disease Validity (ClinGen)
RNU4ATAC spectrum disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 186 VUS of 283 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

283 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic25
VUS186
Likely Benign17
Benign8
Conflicting17
30
Pathogenic
25
Likely Pathogenic
186
VUS
17
Likely Benign
8
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
25
0
25
VUS
0
0
186
0
186
Likely Benign
0
0
17
0
17
Benign
0
0
8
0
8
Conflicting
—17
Total002660283

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

View in ClinVar →

Protein Context — Lollipop Plot

RNU4ATAC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RNU4ATAC-related microcephalic osteodysplastic primordial dwarfism

definitive
ARUndeterminedUncertain
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lowry-Wood syndrome

MIM #226960

Molecular basis of disorder known

Autosomal recessive

Microcephalic osteodysplastic primordial dwarfism, type I

MIM #210710

Molecular basis of disorder known

Autosomal recessive

Roifman syndrome

MIM #616651

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — RNU4ATAC
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical interpretation of variants identified in RNU4ATAC, a non-coding spliceosomal gene.
Benoit-Pilven C et al.·PLoS One
2020
Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing.
Merico D et al.·Nat Commun
2015
Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.
Lionel AC et al.·Genet Med
2018
The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome.
Farach LS et al.·Am J Med Genet A
2018
Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement.
D'Abrusco F et al.·J Med Genet
2025
A Taybi-Linder syndrome-related RTTN variant impedes neural rosette formation in human cortical organoids.
Guguin J et al.·PLoS Genet
2024
Deficiency of the minor spliceosome component U4atac snRNA secondarily results in ciliary defects in human and zebrafish.
Khatri D et al.·Proc Natl Acad Sci U S A
2023Functional
Delineating the phenotype of RNU4ATAC-related spliceosomopathy.
Tabib A et al.·Am J Med Genet A
2023Case report
Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype.
Shelihan I et al.·Hum Genet
2018
Whole genome sequencing identifies pathogenic RNU4ATAC variants in a child with recurrent encephalitis, microcephaly, and normal stature.
McMillan HJ et al.·Am J Med Genet A
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Taybi Linder SyndromeMicrocephalic Osteodysplastic Primordial Dwarfism Types I and IIIRoifman Syndrome

Study of the Pathophysiology of RNU4ATAC and RTTN Associated Syndromes

RECRUITING
NCT06111950Phase NAHospices Civils de LyonStarted 2024-08-27
Blood samplesSkin biopsiesFetal samples
MOPDIIMeier-Gorlin SyndromeSaul-Wilson Syndrome

Primordial Dwarfism Registry

RECRUITING
NCT04569149Nemours Children's ClinicStarted 2008-03-11

External Resources

Links to major genomics databases and tools