BPTF

Chr 17AD

bromodomain PHD finger transcription factor

Also known as: FAC1, FALZ, NEDDFL, NURF301

NCBI Gene: 2186UniProt: Q12830

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]

Primary Disease Associations & Inheritance

{Kaposi sarcoma, susceptibility to}MIM #148000
AD
Neurodevelopmental disorder with dysmorphic facies and distal limb anomaliesMIM #617755
AD
0
Active trials
360
ClinVar variants
16
Pathogenic / LP
3.7
Missense Z· constrained
0.10
LOEUF· LoF intolerant
10
Pubs (2 yr)
Clinical Summary— BPTF
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 222 VUS of 360 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/BPTF?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.03–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.69–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 7 / 132.8Missense obs/exp: 1067 / 1466.8Syn Z: -0.48

ClinVar Variant Classifications

360 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic9
VUS222
Likely Benign113
Benign5
Conflicting4
7
Pathogenic
9
Likely Pathogenic
222
VUS
113
Likely Benign
5
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
2
0
7
Likely Pathogenic
2
4
3
0
9
VUS
0
208
14
0
222
Likely Benign
0
18
31
64
113
Benign
0
1
2
2
5
Conflicting
—4
Total72315266360

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

View in ClinVar →

Protein Context — Lollipop Plot

BPTF · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BPTF-related developmental and speech delay, postnatal microcephaly, and dysmorphic features

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Kaposi sarcoma, susceptibility to}

MIM #148000

Molecular basis of disorder known

Autosomal dominant

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

MIM #617755

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genomic and phenotypic delineation of congenital microcephaly.
Shaheen R et al.·Genet Med
2019
Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.
Glinton KE et al.·Am J Med Genet A
2021
A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants.
Ji J et al.·Cold Spring Harb Mol Case Stud
2019
Bromodomain inhibition targeting BPTF in the treatment of melanoma and other solid tumors.
Khan I et al.·Clin Exp Metastasis
2024Review
Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition.
Mirzaa GM et al.·Nat Commun
2025
Epilepsy as a Novel Phenotype of BPTF-Related Disorders.
Ferretti A et al.·Pediatr Neurol
2024
Classic Kaposi sarcoma: Diagnostics, treatment modalities, and genetic implications - A review of the literature.
Batash R et al.·Acta Oncol
2024Review
Genome-Wide Association Study of Chronic Dizziness in the Elderly Identifies Loci Implicating MLLT10, BPTF, LINC01224, and ROS1.
Clifford R et al.·J Assoc Res Otolaryngol
2023Meta-analysis
Effects of the Missense Variants on Complete Phenotype and Splicing Variant on Severe Growth Retardation in the BPTF Gene.
Ünsel-Bolat G et al.·Dev Neurobiol
2025Case report
Targeting regulation of VEGF by BPTF in non-small cell lung cancer and its potential clinical significance.
Dai M et al.·Eur J Med Res
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
BPTF inhibition antagonizes colorectal cancer progression by transcriptionally inactivating Cdc25A
Guo P et al.·Redox Biol
2022
The effect of growth hormone treatment in children with novel BPTF gene variants: A report of two cases and literature review
Wu W et al.·Mol Genet Genomic Med
2023Review
BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma
Jiang C et al.·Biol Proced Online
2023
Design of Class I/IV Bromodomain-Targeting Degraders for Chromatin Remodeling Complexes
Zahid H et al.·ACS Chem Biol
2023Functional
Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR)
Muñoz Velasco R et al.·Cancers (Basel)
2022
Discovery of High-Affinity Inhibitors of the BPTF Bromodomain.
Lu T et al.·J Med Chem
2021
Synthesis of NVS-BPTF-1 and evaluation of its biological activity.
Mélin L et al.·Bioorg Med Chem Lett
2021
PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer
Gao S et al.·J Transl Med
2023
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients