ARID4B

Chr 1

AT-rich interaction domain 4B

Also known as: BCAA, BRCAA1, RBBP1L1, RBP1L1, SAP180

NCBI Gene: 51742 ENSG00000054267 UniProt: Q4LE39 OMIM: 609696

The protein functions as a transcriptional repressor and is a subunit of the histone deacetylase-dependent SIN3A transcriptional corepressor complex, regulating gene expression involved in cellular proliferation, differentiation, and apoptosis. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly intolerant to loss-of-function variants. The condition affects neurodevelopment and may include additional features given the protein's broad role in transcriptional regulation.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein with sequence similarity to retinoblastoma-binding protein-1. The encoded protein is a subunit of the histone deacetylase-dependant SIN3A transcriptional corepressor complex, which functions in diverse cellular processes including proliferation, differentiation, apoptosis, oncogenesis, and cell fate determination. The gene product is recognized by IgG antibody isolated from a breast cancer patient and appears to be a molecular marker associated with a broad range of human malignancies. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— ARID4B

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 6.67

OE 0.09 (0.05–0.19)

Highly constrained

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

Missense Constraint?

2.29Z-score

OE missense 0.75 (0.69–0.80)

480 obs / 643.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.05–0.19)

0≤0.351.4

Missense OE?0.75 (0.69–0.80)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 6 / 63.2Missense obs/exp: 480 / 643.5Syn Z: 1.09

This gene — mechanism propensity

0.2499th %ile

GOF

0.2198th %ile

LOF

0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.