RBBP7

Chr XX-linked

RB binding protein 7, chromatin remodeling factor

Also known as: RbAp46, SPGFX9

NCBI Gene: 5931 ENSG00000102054 UniProt: Q16576 OMIM: 300825

The RBBP7 protein is a core histone-binding subunit that functions in multiple chromatin remodeling complexes, including histone acetyltransferase, histone deacetylase, and nucleosome remodeling complexes that regulate gene expression and chromatin assembly. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that even single functional copies are critical for normal development.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spermatogenic failure, X-linked, 9MIM #301137

X-linked

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spermatogenic failure, X-linked; no ClinGen or GenCC tier

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

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — RBBP7

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.28LOEUF

pLI 0.984

Z-score 3.59

OE 0.06 (0.02–0.28)

Highly constrained

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

Missense Constraint?

2.79Z-score

OE missense 0.41 (0.34–0.50)

72 obs / 176.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.28)

0≤0.351.4

Missense OE?0.41 (0.34–0.50)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 1 / 17.0Missense obs/exp: 72 / 176.2Syn Z: -0.80

Background carrier burden — how many people carry a rare variant somewhere in RBBP7?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 450

284 rare PASS variants

Rare truncating (LoF)

1 in 8,100

38 rare PASS variants

Rare synonymous (reference)

1 in 340

185 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RBBP7. 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)	~561k	1 in 670	1 in 7,600
South Asian	~36k	1 in 430	1 in 1,700
Remaining (unassigned)	~31k	1 in 350	≈ 1 in 9,400
European (Finnish)	~27k	1 in 1,600	none seen
Admixed American	~23k	1 in 310	≈ 1 in 7,300
African / African American	~21k	1 in 200	1 in 3,400
East Asian	~20k	1 in 410	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,758	1 in 340	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): 11 of 12 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 12.? see exons ↓