BPTF

Chr 17

bromodomain PHD finger transcription factor

Also known as: FAC1, FALZ, NEDDFL, NURF301

NCBI Gene: 2186 ENSG00000171634 UniProt: Q12830

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.

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.10

Clinical Summary— BPTF

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Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

81 unique Pathogenic / Likely Pathogenic· 695 VUS of 1203 total submissions

Explore recent and relevant literature in Research Assistant →

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?

0.10LOEUF

pLI 1.000

Z-score 10.12

OE 0.05 (0.03–0.10)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.71Z-score

OE missense 0.73 (0.69–0.77)

1067 obs / 1466.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.05 (0.03–0.10)

0≤0.351.4

Missense OE?0.73 (0.69–0.77)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 7 / 132.8Missense obs/exp: 1067 / 1466.8Syn Z: -0.48

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongBPTF-related developmental and speech delay, postnatal microcephaly, and dysmorphic featuresLOFAD

This gene — mechanism propensity

0.17100th %ile

GOF

0.15100th %ile

LOF

0.88top 5%

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

LOFprediction above median · 1 literature citation · 85% of P/LP variants are LoF · LOEUF 0.10 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFHaploinsufficiency of the chromatin remodeler BPTF causes syndromic developmental and speech delay, postnatal microcephaly, and dysmorphic features.1

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

References

1.PMID 28942966 ↗

ClinVar Variant Classifications

1203 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43

Likely Pathogenic38

VUS695

Likely Benign289

Benign52

Conflicting45

Pathogenic

Likely Pathogenic

695

VUS

289

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	41	0	2	0	43
Likely Pathogenic	28	10	0	0	38
VUS	7	666	21	1	695
Likely Benign	0	85	47	157	289
Benign	0	18	14	20	52
Conflicting	—				45
Total	76	779	84	178	1,162

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap BPTF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →