RUVBL1

Chr 3

RuvB like AAA ATPase 1

Also known as: ECP-54, ECP54, INO80H, NMP 238, NMP238, PONTIN, Pontin52, RVB1

NCBI Gene: 8607 ENSG00000175792 UniProt: Q9Y265

The protein functions as a DNA-dependent ATPase and helicase that is essential for chromatin remodeling, histone modification, and transcriptional regulation through its role in multiple nuclear complexes including NuA4 and INO80. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and variable features including seizures and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not well tolerated.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.19LOEUF

pLI 0.999

Z-score 4.40

OE 0.04 (0.01–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.39Z-score

OE missense 0.41 (0.35–0.48)

107 obs / 260.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.41 (0.35–0.48)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 1 / 24.5Missense obs/exp: 107 / 260.9Syn Z: -0.72

Background carrier burden — how many people carry a rare variant somewhere in RUVBL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

414 rare PASS variants

Rare truncating (LoF)

1 in 850

29 rare PASS variants

Rare synonymous (reference)

1 in 190

257 rare PASS variants

Rare missense and truncating variants are carried at similar rates in RUVBL1; 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.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 730
South Asian	~43k	1 in 330	1 in 2,300
Remaining (unassigned)	~30k	1 in 270	1 in 980
European (Finnish)	~27k	1 in 480	1 in 3,300
Admixed American	~22k	1 in 160	1 in 4,400
African / African American	~21k	1 in 230	1 in 1,500
East Asian	~20k	1 in 290	1 in 2,100
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 300	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓