BPTF

Chr 17AD

bromodomain PHD finger transcription factor

Also known as: FAC1, FALZ, NEDDFL, NURF301

NCBI Gene: 2186 ENSG00000171634 UniProt: Q12830 OMIM: 601819

The BPTF protein is the largest subunit of the NURF chromatin remodeling complex and catalyzes nucleosome sliding on DNA, which is essential for transcription regulation. Loss-of-function mutations cause autosomal dominant neurodevelopmental disorder with dysmorphic facies and distal limb anomalies. The gene is extremely intolerant to loss-of-function variants, with haploinsufficiency being the likely disease mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene was identified by the reactivity of its encoded protein to a monoclonal antibody prepared against brain homogenates from patients with Alzheimer's disease. Analysis of the original protein (fetal Alz-50 reactive clone 1, or FAC1), identified as an 810 aa protein containing a DNA-binding domain and a zinc finger motif, suggested it might play a role in the regulation of transcription. High levels of FAC1 were detected in fetal brain and in patients with neurodegenerative diseases. The protein encoded by this gene is actually much larger than originally thought, and it also contains a C-terminal bromodomain characteristic of proteins that regulate transcription during proliferation. The encoded protein is highly similar to the largest subunit of the Drosophila NURF (nucleosome remodeling factor) complex. In Drosophila, the NURF complex, which catalyzes nucleosome sliding on DNA and interacts with sequence-specific transcription factors, is necessary for the chromatin remodeling required for transcription. Two alternative transcripts encoding different isoforms have been described completely. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Kaposi sarcoma, susceptibility to}MIM #148000

Neurodevelopmental disorder with dysmorphic facies and distal limb anomaliesMIM #617755

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P