BPTF

Summary

BPTF (bromodomain PHD finger transcription factor, HGNC:3581) is a protein-coding gene on chromosome 17q24.2, encoding Nucleosome-remodeling factor subunit BPTF (Q12830). Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. It is a selective cancer dependency (DepMap: 68.0% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 2186 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 41 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 1,283 total — 45 pathogenic, 44 likely-pathogenic (top 2% of genes corpus-wide)
• Regional missense constraint (gnomAD): 4 of 22 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 27 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 75
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 68.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.09 (highly constrained)
• MANE Select transcript: NM_182641
• Interaction hub: 1,966 STRING partners (top 8% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3581
Approved symbol	BPTF
Name	bromodomain PHD finger transcription factor
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FAC1, NURF301
Ensembl gene	ENSG00000171634
Ensembl biotype	protein_coding
OMIM	601819
Entrez	2186

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000306378

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 6, TSL 3: 5, TSL 5: 3

ENST00000306378, ENST00000321892, ENST00000342579, ENST00000424123, ENST00000467104, ENST00000544491, ENST00000544778, ENST00000577770, ENST00000577837, ENST00000578307, ENST00000579173, ENST00000580465, ENST00000581258, ENST00000582406, ENST00000582467, ENST00000583990, ENST00000584931, ENST00000644067, ENST00001060684, ENST00001060685, ENST00001060686, ENST00001143426

RefSeq mRNA: 8 — MANE Select: NM_182641 NM_001439139, NM_001439140, NM_001439141, NM_001439142, NM_001439143, NM_001439144, NM_004459, NM_182641

CCDS: CCDS11673

Canonical transcript exons

ENST00000306378 — 28 exons

Exon	Start	End
ENSE00001223457	67945409	67946325
ENSE00002431219	67918714	67918838
ENSE00002450094	67929336	67929487
ENSE00002458783	67947726	67947808
ENSE00002460084	67853940	67854762
ENSE00002461925	67893370	67893725
ENSE00002463926	67966572	67966656
ENSE00002465965	67866464	67866687
ENSE00002469197	67944150	67944372
ENSE00002470855	67920015	67920143
ENSE00002474914	67928355	67928601
ENSE00002475711	67891844	67892034
ENSE00002478848	67909582	67909761
ENSE00002481885	67910877	67913187
ENSE00002484050	67931911	67932019
ENSE00002488255	67964212	67964404
ENSE00002491113	67982252	67984378
ENSE00002492370	67903789	67903918
ENSE00002499983	67904702	67904840
ENSE00002506993	67874817	67875020
ENSE00002511387	67922840	67922990
ENSE00002511628	67948081	67948306
ENSE00002534782	67924547	67924589
ENSE00002689718	67825503	67826337
ENSE00002719721	67959541	67959875
ENSE00003489588	67940439	67940656
ENSE00003518015	67975772	67975958
ENSE00003753047	67894034	67894165

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6030 / max 293.3452, expressed in 1812 samples.

Highest expression (Bgee): sural nerve, ventricular zone, cortical plate, ganglionic eminence, corpus callosum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BPTF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	2.4e-30	+0.62	17:67818266:C:G
Brain Cerebellum	eqtl	1.4e-18	+0.32	17:67877653:CTT:C
Brain Cerebellar Hemisphere	eqtl	1.3e-13	+0.26	17:67877653:CTT:C
Nerve Tibial	eqtl	2.9e-08	+0.14	17:67907513:G:A
Cells Cultured fibroblasts	sqtl	6.0e-06	-0.33	17:67913326:A:G
Brain Putamen basal ganglia	eqtl	3.4e-04	+0.21	17:67877653:CTT:C
Cells EBV-transformed lymphocytes	sqtl	3.5e-04	-0.51	17:67826457:CAG:C
Testis	eqtl	4.2e-04	-0.11	17:68083430:T:C
Pituitary	eqtl	9.1e-04	-0.25	17:68163293:T:C
Skin Sun Exposed Lower leg	eqtl	1.1e-03	+0.41	17:67010972:G:A
Artery Aorta	eqtl	1.8e-03	+0.11	17:67961452:A:G
Esophagus Muscularis	eqtl	3.0e-03	+0.10	17:67971446:A:G
Brain Cortex	eqtl	4.1e-03	+0.23	17:67877653:CTT:C
Brain Caudate basal ganglia	eqtl	5.6e-03	+0.17	17:67877653:CTT:C
Brain Nucleus accumbens basal ganglia	eqtl	5.7e-03	+0.18	17:67877653:CTT:C
Esophagus Gastroesophageal Junction	eqtl	7.8e-03	+0.47	17:68798489:TAATC:T
Skin Not Sun Exposed Suprapubic	eqtl	8.8e-03	-0.08	17:67464900:T:C
Brain Spinal cord cervical c-1	eqtl	9.1e-03	+0.25	17:67895948:T:A
Brain Hypothalamus	eqtl	1.0e-02	+0.17	17:67991933:T:C
Brain Hippocampus	eqtl	1.1e-02	+0.15	17:67825050:C:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
162351	24.5050	1804
162352	1.6381	964
162353	0.7017	408
162357	0.6829	359
208357	0.0753	27

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.66	gold quality
ventricular zone	UBERON:0003053	97.54	gold quality
cortical plate	UBERON:0005343	96.95	gold quality
ganglionic eminence	UBERON:0004023	96.32	gold quality
corpus callosum	UBERON:0002336	96.29	gold quality
cerebellar hemisphere	UBERON:0002245	96.08	gold quality
cerebellar cortex	UBERON:0002129	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.98	gold quality
colonic epithelium	UBERON:0000397	95.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.70	gold quality
cerebellum	UBERON:0002037	95.56	gold quality
tonsil	UBERON:0002372	95.14	gold quality
left ovary	UBERON:0002119	94.82	gold quality
trabecular bone tissue	UBERON:0002483	94.72	gold quality
calcaneal tendon	UBERON:0003701	94.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.59	gold quality
adrenal tissue	UBERON:0018303	94.56	gold quality
renal medulla	UBERON:0000362	94.55	gold quality
tibial nerve	UBERON:0001323	94.30	gold quality
pituitary gland	UBERON:0000007	94.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.18	gold quality
lower lobe of lung	UBERON:0008949	94.11	gold quality
right ovary	UBERON:0002118	94.06	gold quality
pylorus	UBERON:0001166	94.05	gold quality
skin of abdomen	UBERON:0001416	93.97	gold quality
body of uterus	UBERON:0009853	93.93	gold quality
skin of leg	UBERON:0001511	93.85	gold quality
endocervix	UBERON:0000458	93.73	gold quality
cardia of stomach	UBERON:0001162	93.71	gold quality
right testis	UBERON:0004534	93.70	gold quality
adenohypophysis	UBERON:0002196	93.64	gold quality
right uterine tube	UBERON:0001302	93.63	gold quality
inferior vagus X ganglion	UBERON:0005363	93.61	gold quality
ovary	UBERON:0000992	93.55	gold quality
skin of hip	UBERON:0001554	93.47	gold quality
left testis	UBERON:0004533	93.41	gold quality
stromal cell of endometrium	CL:0002255	93.34	gold quality
lymph node	UBERON:0000029	93.31	gold quality
pleura	UBERON:0000977	93.25	gold quality
testis	UBERON:0000473	93.24	gold quality
germinal epithelium of ovary	UBERON:0001304	93.18	gold quality
ectocervix	UBERON:0012249	93.18	gold quality
zone of skin	UBERON:0000014	93.17	gold quality
visceral pleura	UBERON:0002401	93.16	gold quality
parietal pleura	UBERON:0002400	93.15	gold quality
bone marrow cell	CL:0002092	93.10	gold quality
subthalamic nucleus	UBERON:0001906	93.05	gold quality
mammalian vulva	UBERON:0000997	93.04	gold quality
postcentral gyrus	UBERON:0002581	92.97	gold quality
fundus of stomach	UBERON:0001160	92.94	gold quality
left uterine tube	UBERON:0001303	92.89	gold quality
entorhinal cortex	UBERON:0002728	92.82	gold quality
endometrium	UBERON:0001295	92.76	gold quality
caput epididymis	UBERON:0004358	92.74	gold quality
lower esophagus mucosa	UBERON:0035834	92.72	gold quality
left lobe of thyroid gland	UBERON:0001120	92.70	gold quality
minor salivary gland	UBERON:0001830	92.65	gold quality
lateral globus pallidus	UBERON:0002476	92.62	gold quality
thyroid gland	UBERON:0002046	92.60	gold quality
nipple	UBERON:0002030	92.59	gold quality
seminal vesicle	UBERON:0000998	92.58	gold quality
right lung	UBERON:0002167	92.57	gold quality
primary visual cortex	UBERON:0002436	92.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.56	gold quality
pigmented layer of retina	UBERON:0001782	92.55	gold quality
retina	UBERON:0000966	92.53	gold quality
mucosa of stomach	UBERON:0001199	92.50	gold quality
tibia	UBERON:0000979	92.45	gold quality
granulocyte	CL:0000094	92.41	gold quality
vagina	UBERON:0000996	92.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.39	gold quality
parietal lobe	UBERON:0001872	92.38	gold quality
urethra	UBERON:0000057	92.31	gold quality
right lobe of thyroid gland	UBERON:0001119	92.31	gold quality
trigeminal ganglion	UBERON:0001675	92.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.26	gold quality
right coronary artery	UBERON:0001625	92.25	gold quality
mouth mucosa	UBERON:0003729	92.24	gold quality
descending thoracic aorta	UBERON:0002345	92.22	gold quality
female reproductive system	UBERON:0000474	92.21	gold quality
spinal cord	UBERON:0002240	92.19	gold quality
metanephros cortex	UBERON:0010533	92.19	gold quality
peritoneum	UBERON:0002358	92.18	gold quality
omental fat pad	UBERON:0010414	92.18	gold quality
uterus	UBERON:0000995	92.04	gold quality
corpus epididymis	UBERON:0004359	91.98	gold quality
stomach	UBERON:0000945	91.97	gold quality
bronchial epithelial cell	CL:0002328	91.95	gold quality
spleen	UBERON:0002106	91.95	gold quality
substantia nigra pars compacta	UBERON:0001965	91.89	gold quality
dorsal root ganglion	UBERON:0000044	91.88	gold quality
bone element	UBERON:0001474	91.84	gold quality
caudate nucleus	UBERON:0001873	91.81	gold quality
occipital lobe	UBERON:0002021	91.80	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.74	gold quality
right frontal lobe	UBERON:0002810	91.73	gold quality
thoracic aorta	UBERON:0001515	91.71	gold quality
upper lobe of lung	UBERON:0008948	91.71	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	440.12
E-MTAB-6524	no	250.27
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	91.0
Hippocampus	tissue	86.9	not detected
Postcentral gyrus	tissue	77.9
Locus coeruleus	tissue	71.9
Choroid plexus	tissue	70.3
Cerebellum	tissue	44.9	medium
Thymus	tissue	44.2
Lymph node	tissue	38.2	not detected
Corpus callosum	tissue	37.2
Hypothalamus	tissue	36.1
Ventral forebrain	tissue	35.1
Olfactory bulb	tissue	34.9
Septum	tissue	34.7
Putamen	tissue	33.7
Amygdala	tissue	33.4
Hippocampal formation	tissue	33.4
Midbrain	tissue	33.2
Prefrontal cortex	tissue	32.8
Cerebral cortex	tissue	32.8	low
Tonsil	tissue	32.6	low
Substantia nigra	tissue	32.3
Periaqueductal gray	tissue	32.3
Motor cortex	tissue	32.0
Skin 1	tissue	31.9	low
Thalamus	tissue	31.9
Somatosensory cortex	tissue	31.5
Basal ganglia	tissue	31.4	medium
Occipital cortex	tissue	31.4
Medulla oblongata	tissue	31.3
Entorhinal cortex	tissue	31.2
Retina	tissue	30.5
Spinal cord	tissue	30.3
Insular cortex	tissue	30.3
Pons	tissue	30.2
Temporal cortex	tissue	30.2
Retrosplenial and cingulate cortex	tissue	30.1
Retrosplenial cortex	tissue	30.0
Pituitary gland	tissue	29.1
Superior colliculi	tissue	29.0
Bone marrow	tissue	27.5	not detected
Testis	tissue	24.8	high
Vagina	tissue	24.5	not detected
Caudate putamen	tissue	24.2
Spleen	tissue	23.3	not detected
Skeletal muscle	tissue	22.3	not detected
Epididymis	tissue	22.3	not detected
Appendix	tissue	22.1	low
Parathyroid gland	tissue	21.9	not detected
Ovary	tissue	21.2	low
Breast	tissue	20.5	low
Stomach 1	tissue	19.8	medium
Endometrium 1	tissue	19.3	low
Cervix	tissue	18.5	not detected
Rectum	tissue	18.5	medium
Thyroid gland	tissue	18.4	medium
Colon	tissue	18.0	medium
Tongue	tissue	17.6
Frontal cortex	tissue	17.5
Prostate	tissue	17.1	not detected
Pancreas	tissue	16.7	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Flocculonodular lobe (178.6), Cerebellar cortex (169.7), Vermis (157.3), Orbitofrontal gyrus, anterior (119.1), Temporal white matter (112.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
EN1
EN2
HOXC8	Unknown
MAZ

miRNA regulators (miRDB)

Targeting BPTF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 257 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.09, missense Z 5.09 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000306378 splits into 22 regions with different missense tolerance; 4 are missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:67,825,725–67,825,856	31 / 53.6	0.58	no
17:67,825,857–67,826,038	103 / 72.1	1.43	no
17:67,826,039–67,854,009	153 / 178.3	0.86	no
17:67,854,010–67,854,522	102 / 212.6	0.48	no
17:67,854,523–67,854,760	22 / 97.3	0.23	yes (p 2.2e-14)
17:67,854,761–67,891,925	187 / 201.5	0.93	no
17:67,891,926–67,891,981	5 / 22.0	0.23	yes (p 2.9e-04)
17:67,891,982–67,893,529	63 / 84.1	0.75	no
17:67,893,530–67,904,820	99 / 227.1	0.44	no
17:67,904,821–67,912,529	713 / 714.9	1.00	no
17:67,912,530–67,912,973	144 / 177.2	0.81	no
17:67,912,974–67,913,120	24 / 57.5	0.42	no
17:67,913,121–67,918,729	36 / 34.7	1.04	no
17:67,918,730–67,918,799	6 / 28.2	0.21	yes (p 2.9e-05)
17:67,918,800–67,929,420	198 / 277.1	0.71	no
17:67,929,421–67,947,804	570 / 633.5	0.90	no
17:67,947,805–67,948,223	26 / 60.6	0.43	no
17:67,948,224–67,959,838	148 / 145.5	1.02	no
17:67,959,839–67,966,611	48 / 114.2	0.42	no
17:67,966,612–67,975,781	0 / 24.3	0.00	yes (p 8.1e-07)
17:67,975,782–67,975,949	27 / 66.1	0.41	no
17:67,975,950–67,982,285	21 / 16.1	1.30	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 68.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): LOU-NH91 (-1.801), NCI-H82 (-1.476), NCI-H522 (-1.46), DB (-1.433), KMS-27 (-1.399), TALL-1 (-1.356), EM-2 (-1.347), SNU-308 (-1.341), MEL-HO (-1.337), UACC-62 (-1.31), MHH-ES-1 (-1.307), Malme-3M (-1.305), SNU-626 (-1.299), AML-193 (-1.285), COV434 (-1.284).

Literature-anchored findings (GeneRIF, showing 25)

• hkelch-like ECH-associated protein 1 regulates FAC1 in addition to its known role in control of Nrf2 (PMID:15379550)
• These findings suggest a role for FAC1 in apoptosis following release of Nrf2 from Keap1 in response to oxidative stress. (PMID:16137655)
• crystallographic and NMR structures of the bromodomain-proximal PHD finger of BPTF in free and H3(1-15)K4me3-bound states (PMID:16728978)
• High FALZ expression is associated with metastatic spread to the brain in primary non-small cell lung cancer. (PMID:19190132)
• the novel translocation breakpoint within the BPTF gene is associated with a pre-malignant phenotype (PMID:20300178)
• The PHD-adjacent bromodomain in BPTF binds with marked selectivity H4K16ac, in combination with H3K4me3 at the mononucleosome level. (PMID:21596426)
• expression may be marker for survival prediction in hepatocellular carcinoma (PMID:25362514)
• High BPTF expression was significantly correlated with tumor progression and may be a potent prognostic marker of colorectal cancer. (PMID:25716692)
• BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers (PMID:26418899)
• somatic frameshift mutations of BPTF were present in gastric cancer and colorectal cancers (PMID:26899553)
• NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). (PMID:27026195)
• Overexpression of BPTF is associated with melanoma cell survival and progression. (PMID:27185926)
• Two new signals were observed at genome-wide significance (P < 5 x 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases (PMID:28025329)
• Haploinsufficiency of BPTF gene is associated with Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features. (PMID:28942966)
• Study identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. (PMID:29763634)
• data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers (PMID:30481052)
• High BPTF expression in glioma tissue specimens was significantly associated with WHO grade and tumor size. Survival analysis revealed that the BPTF highexpression group had poorer overall and progressionfree survival compared with the lowexpression group. (PMID:30542695)
• High BPTF expression is associated with gastric cancer growth and invasion. (PMID:30922402)
• Upregulation of bromodomain PHD finger transcription factor in ovarian cancer and its critical role for cancer cell proliferation and survival. (PMID:32985220)
• Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. (PMID:33664855)
• The effect of growth hormone treatment in children with novel BPTF gene variants: A report of two cases and literature review. (PMID:36153657)
• Targeting regulation of VEGF by BPTF in non-small cell lung cancer and its potential clinical significance. (PMID:36529788)
• PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer. (PMID:36967443)
• A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma. (PMID:38380509)
• NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation. (PMID:38940430)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bptf	ENSDARG00000077361
mus_musculus	Bptf	ENSMUSG00000040481
rattus_norvegicus	Bptf	ENSRNOG00000047296
drosophila_melanogaster	E(bx)	FBGN0000541

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2A (ENSG00000108773), KAT2B (ENSG00000114166), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD4 (ENSG00000141867), BRD3 (ENSG00000169925), BAZ1A (ENSG00000198604), BRD2 (ENSG00000204256)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2444008) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 48 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased embryo size	2
embryonic growth arrest	2
abnormal rostral-caudal axis patterning	2
decreased cell proliferation	1
forebrain hypoplasia	1
abnormal cerebral cortex morphology	1
abnormal cerebral cortex lamination	1
decreased body length	1
decreased body weight	1
abnormal ectoderm development	1
absent mesoderm	1
abnormal endoderm development	1
failure of primitive streak formation	1
abnormal proximal-distal axis patterning	1
abnormal developmental patterning	1
abnormal extraembryonic tissue morphology	1
decreased brain weight	1
abnormal primitive streak formation	1
increased susceptibility to bacterial infection	1
small ectoplacental cone	1
abnormal chorion morphology	1
abnormal neuron specification	1
abnormal egg cylinder morphology	1
abnormal digestive system development	1
increased neuron apoptosis	1

+23 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2Y0Q2	100.0%	Diamond
Oryza sativa Japonica Group	Q2R837	100.0%	Diamond
Pongo abelii	Q5R8B0	99.7%	Diamond
Bos taurus	Q32S26	97.6%	Diamond
Canis lupus familiaris	Q5TJG6	97.1%	Diamond
Macaca fascicularis	Q4R8Y1	95.9%	Diamond
Mesocricetus auratus	Q60544	95.4%	Diamond
Xenopus laevis	Q6GLP7	94.2%	Diamond
Xenopus tropicalis	Q6NVM8	94.2%	Diamond
Gallus gallus	P58268	93.3%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CXW4	88.7%	Diamond
Eremothecium gossypii ATCC 10895	Q756G9	88.6%	Diamond
Saccharomyces cerevisiae S288C	Q03330	88.3%	Diamond
Nakaseomyces glabratus CBS 138	Q6FTW5	88.3%	Diamond
Arabidopsis thaliana	Q710E8	87.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORA38B	snoRNA	100124536
NOL11	protein-coding	25926
C17orf58	protein-coding	284018
TRR-CCG2-1	tRNA	7233
PITPNC1	protein-coding	26207
KPNA2	protein-coding	3838

Protein

Protein identifiers

Nucleosome-remodeling factor subunit BPTF — Q12830 (reviewed: Q12830)

Alternative names: Bromodomain and PHD finger-containing transcription factor, Fetal Alz-50 clone 1 protein, Fetal Alzheimer antigen

All UniProt accessions (11): Q12830, A0A2R8Y7Q1, E7ETD6, E9PE19, F5GXF5, F5H176, J3KSK9, J3KSY0, J3QLW4, J3QQK4, J3QQQ8

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. The NURF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NURF-5 ISWI chromatin remodeling complex. Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development. Histone-binding protein which binds to H3 tails trimethylated on ‘Lys-4’ (H3K4me3), which mark transcription start sites of active genes. Binds to histone H3 tails dimethylated on ‘Lys-4’ (H3K4Me2) to a lesser extent. May also regulate transcription through direct binding to DNA or transcription factors.

Subunit / interactions. Interacts with MAZ. Interacts with KEAP1. Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1 (isoform 2), BPTF, RBBP4 and RBBP7. Within the complex interacts with isoform 2 of SMARCA1. Component of the BPFT-SMARCA1 complex at least composed of SMARCA1 (isoform 1), BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin. Within the complex interacts with isoform 1 of SMARCA1. Component of the NURF-5 ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H and BPTF. Within NURF-5 ISWI chromatin remodeling complex interacts with SMARCA5/SNF2H.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed, with highest levels in testis. Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex (at protein level).

Post-translational modifications. Phosphorylation enhances DNA-binding. Highly susceptible to proteolysis.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) [MIM:617755] An autosomal dominant neurodevelopmental disorder characterized by variable degrees of developmental delay, intellectual disability, speech delay, postnatal microcephaly, dysmorphic features, and mild abnormalities of the hands and feet. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The second PHD-type zinc finger mediates binding to histone H3K4Me3. Has specificity for trimethyllysine; introducing a mutation in the Tyr-2876 residue can induce binding to dimethyllysine.

Similarity. Belongs to the PBTF family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12830-1	1	yes
Q12830-2	2
Q12830-4	4

RefSeq proteins (8): NP_001426068, NP_001426069, NP_001426070, NP_001426071, NP_001426072, NP_001426073, NP_004450, NP_872579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018359	Bromodomain_CS	Conserved_site
IPR018501	DDT_dom	Domain
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR028941	WHIM2_dom	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR038028	BPTF	Family

Pfam: PF00439, PF00628, PF02791, PF15613

UniProt features (131 total): compositionally biased region 35, sequence conflict 17, region of interest 16, modified residue 16, helix 13, mutagenesis site 8, coiled-coil region 4, site 4, cross-link 4, sequence variant 3, domain 2, turn 2, strand 2, zinc finger region 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

showing 30 of 46 structures by resolution:

PDB	Title	Method	Resolution (Å)
8AG2	Crystal structure of the BPTF bromodomain in complex with BI-7190	X-RAY DIFFRACTION	1.02
5R4O	PanDDA analysis group deposition of ground-state model of BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.05
5R4M	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.11
5R4L	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.13
5R4K	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.17
5R4H	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.18
7K6S	Crystal structure of the bromodomain (BD) of human Bromodomain and PHD finger-containing …	X-RAY DIFFRACTION	1.23
5R4G	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.25
5R4I	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.28
5R4N	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.28
9ZUK	Crystal structure of BPTF bromodomain bound to BZ1	X-RAY DIFFRACTION	1.35
5R4J	PanDDA analysis group deposition – CRYSTAL STRUCTURE OF THE BROMODOMAIN OF HUMAN …	X-RAY DIFFRACTION	1.39
7LPK	Crystal structure of BPTF bromodomain in complex with inhibitor HZ-03-112	X-RAY DIFFRACTION	1.39
7RWN	Crystal Structure of BPTF bromodomain in complex with …	X-RAY DIFFRACTION	1.39
7LRK	Crystal structure of BPTF bromodomain in complex with inhibitor Pdy-3-093	X-RAY DIFFRACTION	1.44
2RI7	Crystal structure of PHD finger-linker-bromodomain Y17E mutant from human BPTF in the …	X-RAY DIFFRACTION	1.45
7LRO	Crystal structure of BPTF bromodomain in complex with inhibitor HZ-01-105	X-RAY DIFFRACTION	1.45
3QZT	Crystal Structure of BPTF bromo in complex with histone H4K16ac - Form II	X-RAY DIFFRACTION	1.5
7KDZ	Crystal structure of the bromodomain (BD) of human Bromodomain and PHD finger-containing …	X-RAY DIFFRACTION	1.54
7F5D	Crystal structure of BPTF-BRD with ligand DC-BPi-03 bound	X-RAY DIFFRACTION	1.57
3UV2	Crystal structure of the bromodomain of human nucleosome-remodeling factor subunit BPTF	X-RAY DIFFRACTION	1.58
7RWO	Crystal Structure of BPTF bromodomain in complex with …	X-RAY DIFFRACTION	1.58
7K6R	Crystal structure of the bromodomain (BD) of human Bromodomain and PHD finger-containing …	X-RAY DIFFRACTION	1.6
8OU2	Crystal structure of the bromodomain of human Bromodomain and PHD finger-containing …	X-RAY DIFFRACTION	1.6
7LP0	Crystal structure of BPTF bromodomain in complex with inhibitor Pdy-3-077	X-RAY DIFFRACTION	1.66
7KDW	Crystal structure of the bromodomain (BD) of human Bromodomain and PHD finger-containing …	X-RAY DIFFRACTION	1.71
7RWP	Crystal Structure of BPTF bromodomain in complex with …	X-RAY DIFFRACTION	1.73
7M2E	Crystal structure of BPTF bromodomain in complex with CB02-092	X-RAY DIFFRACTION	1.75
3QZS	Crystal Structure of BPTF bromo in complex with histone H4K16ac - Form I	X-RAY DIFFRACTION	1.8
7VD4	Crystal structure of BPTF-BRD with ligand TP248 bound	X-RAY DIFFRACTION	1.86

Predicted structure (AlphaFold)

No AlphaFold model available for Q12830 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4)

Position	Role
2869	histone h3k4me3 binding
2876	histone h3k4me3 binding
2882	histone h3k4me3 binding
2891	histone h3k4me3 binding

Post-translational modifications (20)

Type	Positions
Phosphoserine	216, 572, 763, 817, 1231, 1300, 1310, 2098, 2465
N6-acetyllysine	880
Phosphothreonine	1064, 1303
Omega-n-methylarginine	2155
Asymmetric dimethylarginine	2162, 2184, 2191
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	1088, 1138, 1209, 1730

Mutagenesis-validated functional residues (8)

Position	Phenotype
2869	abolishes binding to histone h3k4me3.
2876	induces binding to histone h3k4me2.
2876	strongly reduces binding to histone h3k4me3.
2882	abolishes binding to histone h3k4me3.
2884	strongly reduces binding to histone h3k4me3.
2886	abolishes binding to histone h3k4me3.
2889	strongly reduces binding to histone h3k4me3.
2891	abolishes binding to histone h3k4me3.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 432 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GCANCTGNY_MYOD_Q6, CTATGCA_MIR153, AATGGAG_MIR136, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, PATIL_LIVER_CANCER, GOBP_RESPONSE_TO_NERVE_GROWTH_FACTOR, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, CATTTCA_MIR203, SOX9_B1, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_ENDODERM_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), brain development (GO:0007420), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to nerve growth factor stimulus (GO:1990090), chromatin organization (GO:0006325), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (5): zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), metal ion binding (GO:0046872)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), NURF complex (GO:0016589), dendrite (GO:0030425), cell body (GO:0044297), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062)

GO top-level categories

35 GO namespaces:

Category	Terms
cellular anatomical structure	6
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
chromatin organization	1
gene expression	1
RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
positive regulation of DNA-templated transcription	1
cellular response to growth factor stimulus	1
response to nerve growth factor	1
cellular component organization	1
negative regulation of RNA biosynthetic process	1
transition metal ion binding	1
DNA binding	1
binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
ATP-dependent activity	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
ISWI-type complex	1
neuron projection	1
dendritic tree	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
brain development	BP	mutant phenotype
chromatin remodeling	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	mutant phenotype
regulation of DNA-templated transcription	BP	direct assay
regulation of transcription by RNA polymerase II	BP	mutant phenotype
NURF complex	CC	direct assay
chromatin	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
sequence-specific DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,966 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPTF	SMARCA1	P28370	881
BPTF	ING2	Q9H160	755
BPTF	ING3	Q9NXR8	713
BPTF	SMARCA5	O60264	712
BPTF	WDR5	P61964	680
BPTF	KDM4A	O75164	586
BPTF	HOXC8	P31273	573
BPTF	H2AZ1	P0C0S5	563
BPTF	SETD1A	O15047	557
BPTF	DNMT3L	Q9UJW3	557
BPTF	MORF4L1	Q9UBU8	545
BPTF	DOT1L	Q8TEK3	504
BPTF	DNAH8	Q96JB1	499
BPTF	CHD1	O14646	494
BPTF	PRMT6	Q96LA8	489

IntAct

Human interaction partners of BPTF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
SMARCA1	association	0.750	2
SMARCA5	physical association	0.560	1
DPY30	association	0.530	1
H4C16	direct interaction	0.440	3
H2BC9	physical association	0.400	1
H3-3A	physical association	0.400	1
RPS4X	physical association	0.400	1
SQSTM1	physical association	0.370	1
EN1	association	0.350	1
EN2	association	0.350	1
IL1A	association	0.350	1

BioGRID (270 interactions; top human partners by supporting records): RBBP4 (Affinity Capture-MS; 7 records), RBBP7 (Affinity Capture-MS; 6 records), C17orf49 (Affinity Capture-MS; 5 records), HIST1H3A (Proximity Label-MS; 5 records), HIST1H4I (Reconstituted Complex; 5 records), KEAP1 (Negative Genetic; 5 records), SMARCA1 (Affinity Capture-MS; 5 records), MAZ (Two-hybrid; 4 records), H3F3A (Proximity Label-MS; 3 records), HMGXB4 (Affinity Capture-MS; 3 records), SMARCA5 (Affinity Capture-MS; 3 records), BANF1 (Cross-Linking-MS (XL-MS); 2 records), BRD3 (Affinity Capture-MS; 2 records), BUB1 (Affinity Capture-MS; 2 records), CHD4 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
BPTF	“form complex”	HNuRF	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
hNURF complex	4	BPTF, RBBP4, RBBP7, SMARCA1

Disease & clinical

Genetic variants

Variant evidence for BPTF: 1,283 ClinVar records (89 pathogenic / likely pathogenic); 41 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,283 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	44
Uncertain significance	747
Likely benign	282
Benign	41

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 89 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
828184	NM_182641.4(BPTF):c.255del (p.Ser86fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1693493	NM_182641.4(BPTF):c.209dup (p.Ser71fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
3679943	NM_182641.4(BPTF):c.8572C>T (p.Arg2858Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
985444	NM_182641.4(BPTF):c.2346_2349del (p.Thr783fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3381404	NM_182641.4(BPTF):c.2521C>T (p.Arg841Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
431065	NM_182641.4(BPTF):c.4838_4839del (p.Val1613fs)	Pathogenic	criteria provided, single submitter	3
431072	NM_182641.4(BPTF):c.989del (p.Leu330fs)	Pathogenic	criteria provided, single submitter	3
431073	NM_182641.4(BPTF):c.2366del (p.Asn789fs)	Pathogenic	criteria provided, single submitter	2
504258	NM_182641.4(BPTF):c.6622C>T (p.Arg2208Ter)	Pathogenic	criteria provided, single submitter	1
598947	NM_182641.4(BPTF):c.5337_5338del (p.Val1780fs)	Pathogenic	criteria provided, single submitter	1
817147	NM_182641.4(BPTF):c.2245dup (p.Arg749fs)	Pathogenic	criteria provided, single submitter	1
817267	NM_182641.4(BPTF):c.5649del (p.Ile1883fs)	Pathogenic	criteria provided, single submitter	1
817342	NM_182641.4(BPTF):c.3302del (p.Asn1101fs)	Pathogenic	criteria provided, single submitter	1
985493	NM_182641.4(BPTF):c.1447dup (p.Thr483fs)	Pathogenic	criteria provided, single submitter	1
1071837	NM_182641.4(BPTF):c.4469del (p.Ser1490fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore BPTF’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 2,780):

Position(s)	Effect	Δscore	Sites
17:67853939	acceptor_loss	1.0000	3
17:67866688–67866689	donor_loss	1.0000	5
17:67874807–67874811	acceptor_gain	1.0000	3
17:67874814	acceptor_gain	1.0000
17:67874815–67874816	acceptor_loss	1.0000	4
17:67875010	donor_gain	1.0000
17:67875021–67875022	donor_loss	1.0000	6
17:67886313	donor_gain	1.0000
17:67886317–67886318	donor_loss	1.0000	5
17:67891842–67891843	acceptor_loss	1.0000	5

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 19,204 scored), across 1,331 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1909	9	0.936	0.998
M939	9	0.934	0.997
M531	9	0.924	0.996
M2323	9	0.917	0.999
H413	8	1.000	1.000
D391	8	0.999	1.000
H392	8	0.999	1.000
D312	8	0.998	1.000
D390	8	0.998	1.000
D401	8	0.998	1.000
H1016	8	0.998	1.000
D235	8	0.997	0.999
D464	8	0.997	0.999
H929	8	0.997	1.000
D872	8	0.996	0.999
D309	8	0.995	0.999
H397	8	0.995	1.000
H923	8	0.994	1.000
F946	8	0.994	1.000
F2335	8	0.994	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (validation)	favorable	0.000174

Disease associations

OMIM: gene MIM:601819 | disease phenotypes: MIM:617755

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
syndromic intellectual disability	Strong	Autosomal dominant
neurodevelopmental disorder with dysmorphic facies and distal limb anomalies	Strong	Autosomal dominant	3

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Severe microcephaly	green

Mondo (4): neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (MONDO:0060596), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), syndromic intellectual disability (MONDO:0000508)

Orphanet (2): BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome (Orphanet:686482), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 75 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000076	Vesicoureteral reflux
HP:0000160	Narrow mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000362	Otosclerosis
HP:0000403	Recurrent otitis media
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000455	Broad nasal tip
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000664	Synophrys
HP:0000692	Tooth malposition
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000718	Aggressive behavior
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000869	Secondary amenorrhea
HP:0000969	Edema
HP:0001034	Hypermelanotic macule
HP:0001238	Slender finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001531	Failure to thrive in infancy
HP:0001642	Pulmonic stenosis
HP:0001657	Prolonged QT interval
HP:0001763	Pes planus
HP:0001845	Overlapping toe
HP:0001852	Sandal gap
HP:0001956	Truncal obesity
HP:0002500	Abnormal cerebral white matter morphology
HP:0002650	Scoliosis
HP:0002664	Neoplasm
HP:0002967	Cubitus valgus
HP:0003019	Abnormality of the wrist
HP:0003028	Abnormality of the ankle
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0008551	Microtia
HP:0008607	Progressive conductive hearing impairment
HP:0008935	Generalized neonatal hypotonia

GWAS associations

showing 30 of 41 associations:

Study	Trait	p-value
GCST90013407_173	Liver enzyme levels (gamma-glutamyl transferase)	5e-39
GCST90011898_138	Alanine aminotransferase levels	4e-21
GCST010244_99	Triglyceride levels	3e-20
GCST004606_144	Eosinophil count	6e-19
GCST004600_147	Eosinophil percentage of white cells	9e-18
GCST004624_9	Sum eosinophil basophil counts	2e-17
GCST004617_54	Eosinophil percentage of granulocytes	4e-17
GCST005830_38	Hand grip strength	1e-16
GCST010703_226	Brain morphology (MOSTest)	1e-15
GCST010173_57	Triglyceride levels	6e-15
GCST004623_52	Neutrophil percentage of granulocytes	8e-15
GCST003605_5	EGFR mutation-positive lung adenocarcinoma	2e-12
GCST010988_170	Adult body size	2e-12
GCST005829_17	Hand grip strength	5e-12
GCST004904_134	Body mass index	6e-12
GCST006976_61	Macular thickness	7e-12
GCST010002_357	Refractive error	7e-12
GCST006611_136	HDL cholesterol	3e-11
GCST009379_65	Type 2 diabetes	3e-11
GCST001609_3	Lung adenocarcinoma	7e-11
GCST008839_432	Height	7e-11
GCST90000047_166	Age at first sexual intercourse	1e-10
GCST004904_59	Body mass index	5e-10
GCST006924_5	Loneliness (MTAG)	1e-9
GCST008834_3	Non-small cell lung cancer	2e-9
GCST010243_25	Apolipoprotein B levels	3e-9
GCST006923_13	Loneliness	6e-9
GCST009463_10	Loneliness	7e-9
GCST009602_52	Metabolic syndrome	8e-9
GCST007323_50	Risk-taking tendency (4-domain principal component model)	1e-8

EFO canonical traits (from GWAS)

19 canonical traits:

EFO ID	Trait name
EFO:0007835	alcohol dependence measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004340	body mass index
EFO:0006941	grip strength measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0008579	risk-taking behaviour
EFO:0000195	metabolic syndrome
EFO:0004530	triglyceride measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004346	neuroimaging measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3085621 (SINGLE PROTEIN), CHEMBL6195548 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,756 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL513909	BI-2536	2	932
CHEMBL130880	IPIDACRINE	2	824

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
MS363	Inhibition	5.79	pKi

Binding affinities (BindingDB)

75 measured of 93 human assays (95 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4861491	KD	0.24 nM
CHEMBL4873093	IC50	16 nM
CHEMBL4860578	IC50	16 nM
CHEMBL3785432	IC50	19 nM
CHEMBL4870170	IC50	29 nM
CHEMBL4461619	IC50	30 nM
CHEMBL4867072	IC50	33 nM
CHEMBL4868713	IC50	37 nM
CHEMBL4851594	IC50	59 nM
CHEMBL4866637	IC50	59 nM
CHEMBL4862619	IC50	64 nM
CHEMBL4780673	KD	71 nM
CHEMBL3590408	IC50	100 nM
CHEMBL4069412	KI	100 nM
CHEMBL5079885	IC50	100 nM
CHEMBL4574669	KD	105 nM
CHEMBL4852588	IC50	114 nM
CHEMBL4873042	EC50	120 nM
CHEMBL4853486	IC50	145 nM
CHEMBL4861221	IC50	157 nM
CHEMBL3590405	IC50	158 nM
CHEMBL4848138	IC50	170 nM
CHEMBL3590389	IC50	200 nM
CHEMBL4848701	KD	230 nM
CHEMBL4850516	IC50	250 nM
CHEMBL4863921	IC50	288 nM
CHEMBL4870218	IC50	310 nM
CHEMBL4583297	IC50	316 nM
CHEMBL4848082	IC50	370 nM
CHEMBL4846718	KD	428 nM
CHEMBL4861375	IC50	698 nM
CHEMBL4850913	IC50	700 nM
CHEMBL4863529	IC50	790 nM
CHEMBL4855881	IC50	800 nM
CHEMBL4877118	IC50	970 nM
4-[4-[(dimethylamino)methyl]-3,5-dimethoxyphenyl]-2-methyl-2,7-naphthyridin-1-one	KD	1000 nM	US-11773085: Methods and compounds for treating disorders
CHEMBL4101756	IC50	1000 nM
CHEMBL4872350	IC50	1700 nM
CHEMBL4872422	KD	1800 nM
CHEMBL4872974	IC50	2100 nM
CHEMBL4065579	IC50	2510 nM
CHEMBL4861822	IC50	3200 nM
CHEMBL3086883	KI	3290 nM
CHEMBL3086885	KI	3300 nM
CHEMBL4858548	IC50	3900 nM
CHEMBL4872107	IC50	7700 nM
CHEMBL4863800	IC50	7800 nM
CHEMBL4853420	IC50	8700 nM
(E)-6-(but-2-en-1-yl)-4-(4-(2-hydroxypropan-2-yl)-2,5-dimethoxyphenyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one	KD	9300 nM
TCMDC-133606	IC50	10000 nM

ChEMBL bioactivities

79 potent at pChembl≥5 of 110 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.20	Kd	6.3	nM	CHEMBL4872300
8.03	Kd	9.3	nM	CHEMBL4861491
7.80	IC50	16	nM	CHEMBL4873093
7.80	IC50	16	nM	CHEMBL4860578
7.80	IC50	16	nM	CHEMBL4780673
7.57	IC50	26.9	nM	CHEMBL4873042
7.54	IC50	28.8	nM	CHEMBL4870170
7.52	IC50	30	nM	CHEMBL4873093
7.52	IC50	30	nM	CHEMBL4780673
7.49	IC50	32.7	nM	CHEMBL4867072
7.44	IC50	36	nM	CHEMBL4861491
7.43	IC50	36.9	nM	CHEMBL4868713
7.41	IC50	39	nM	CHEMBL6189123
7.25	IC50	56	nM	CHEMBL4848701
7.23	IC50	59.3	nM	CHEMBL4851594
7.23	IC50	58.6	nM	CHEMBL4866637
7.20	IC50	63.8	nM	CHEMBL4862619
7.17	IC50	67	nM	CHEMBL4872300
7.16	Kd	70	nM	CHEMBL4848701
7.15	Kd	71	nM	CHEMBL4873093
7.15	Kd	71	nM	CHEMBL4780673
7.00	Kd	100	nM	CHEMBL3823478
6.94	IC50	113.8	nM	CHEMBL4852588
6.92	EC50	120	nM	CHEMBL4873042
6.92	Kd	120	nM	CHEMBL4461619
6.89	Ki	130	nM	CHEMBL4069412
6.84	IC50	145.4	nM	CHEMBL4853486
6.80	IC50	157.3	nM	CHEMBL4861221
6.77	IC50	170	nM	CHEMBL4848138
6.70	Kd	200	nM	CHEMBL4863631
6.70	Kd	200	nM	CHEMBL4461619
6.66	IC50	220	nM	CHEMBL4101756
6.64	EC50	228	nM	CHEMBL4461619
6.60	IC50	250	nM	CHEMBL4850516
6.54	IC50	290	nM	CHEMBL4866748
6.54	IC50	287.6	nM	CHEMBL4863921
6.51	IC50	310	nM	CHEMBL4870218
6.46	IC50	350	nM	CHEMBL4461619
6.43	IC50	370	nM	CHEMBL4848082
6.42	IC50	380	nM	CHEMBL4863631
6.37	Kd	428	nM	CHEMBL4846718
6.37	IC50	430	nM	CHEMBL4461619
6.26	IC50	550	nM	CHEMBL4877696
6.16	IC50	700	nM	CHEMBL4850913
6.16	IC50	698.3	nM	CHEMBL4861375
6.10	IC50	800	nM	CHEMBL4855881
6.10	IC50	790	nM	CHEMBL4863529
6.04	Kd	917	nM	CHEMBL4574669
6.02	IC50	950	nM	CHEMBL4065579
6.01	IC50	970	nM	CHEMBL4877118

PubChem BioAssay actives

67 with measured affinity, of 219 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[4-(2-aminoethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769023: Binding affinity to BPTF (unknown origin) by by BROMOscan method	kd	0.0063	uM
5-[4-(2-aminoethyl)anilino]-4-bromo-2-methylpyridazin-3-one	1769023: Binding affinity to BPTF (unknown origin) by by BROMOscan method	kd	0.0093	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfonyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0160	uM
7-(1-cyclopropylpyrazol-4-yl)-2-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylanilino]-3-methyl-1,9a-dihydropyrido[1,2-a]pyrimidin-4-one	1764122: Inhibition of BPTF in human HEK293 cells by NanoBRET assay	ic50	0.0160	uM
N,N-dimethyl-3-[5-(2-methylsulfonyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)indol-1-yl]propan-1-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0269	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-N-ethyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0288	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0327	uM
6-[1-[2-(dimethylamino)ethyl]indol-5-yl]-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0369	uM
2-[3-[4-[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]piperazin-1-yl]propoxy]-5-[2-methylsulfonyl-6-(propylamino)pyrimidin-4-yl]benzonitrile	2274453: PROTAC activity at human BPTF/CRBN in human MV4-11 cells assessed as degradation of protein measured after 24 hrs by immunoblotting analysis	ic50	0.0390	uM
4-chloro-5-[4-[3-(dimethylamino)propyl]anilino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.0560	uM
6-[1-[3-(dimethylamino)propyl]-3-methylindol-5-yl]-2-methylsulfonyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0586	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-N-methyl-2-methylsulfinylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0593	uM
6-[1-[3-(dimethylamino)propyl]-7-methoxyindol-5-yl]-2-methylsulfonyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0638	uM
7-(1-cyclopropylpyrazol-4-yl)-2-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylanilino]-3-methylpyrido[1,2-a]pyrimidin-4-one	1770707: Binding affinity to BPTF (unknown origin)	kd	0.0710	uM
4-[4-[(dimethylamino)methyl]-3,5-dimethoxyphenyl]-2-methyl-2,7-naphthyridin-1-one	2191061: Binding affinity to FALZ (unknown origin) assessed as dissociation constant by bromoKdselect analysis	kd	0.1000	uM
N-butyl-6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.1138	uM
6-[4-[3-(dimethylamino)propoxy]phenyl]-2-methylsulfonyl-N-(3-pyrazol-1-ylpropyl)pyrimidin-4-amine	1770707: Binding affinity to BPTF (unknown origin)	kd	0.1200	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfinyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.1454	uM
N,N-dimethyl-3-[3-methyl-5-(2-methylsulfonyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)indol-1-yl]propan-1-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.1573	uM
4-chloro-5-[4-[2-(dimethylamino)ethyl]anilino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.1700	uM
2-[4-[4-(aminomethyl)anilino]-5-chloro-6-oxopyridazin-1-yl]acetonitrile	1769023: Binding affinity to BPTF (unknown origin) by by BROMOscan method	kd	0.2000	uM
5-[2-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.2200	uM
4-chloro-2-methyl-5-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.2500	uM
N-butan-2-yl-6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.2876	uM
5-[4-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.2900	uM
4-chloro-5-[4-[(dimethylamino)methyl]anilino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.3100	uM
4-chloro-2-methyl-5-(1,2,3,4-tetrahydroisoquinolin-7-ylamino)pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.3700	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	1764118: Binding affinity to BPTF (unknown origin) by isothermal titration calorimetry	kd	0.4280	uM
5-[4-(aminomethyl)anilino]-4-chloro-2-ethylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.5500	uM
6-(1H-indol-5-yl)-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.6983	uM
4-chloro-5-(4-fluoroanilino)-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.7000	uM
5-[4-(aminomethyl)anilino]-4-chloro-2-propan-2-ylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.7900	uM
5-[3-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.8000	uM
2-[[(3R,5R)-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554037: Binding affinity to human N-terminal His-tagged FALZ by isothermal titration calorimetry	kd	0.9170	uM
5-anilino-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.9500	uM
N-[[4-[(5-chloro-1-methyl-6-oxopyridazin-4-yl)amino]phenyl]methyl]acetamide	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.9700	uM
4-bromo-2-methyl-5-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	1.5000	uM
4-[(2-amino-3-chloro-4-hydroxy-5-methylphenyl)diazenyl]-N-pyridin-2-ylbenzenesulfonamide	1054708: Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	ki	1.6200	uM
4-[(2-amino-4-hydroxy-3,5-dimethylphenyl)diazenyl]-N-pyridin-2-ylbenzenesulfonamide	1054708: Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	ki	1.7000	uM
N-methyl-2-methylsulfonyl-6-quinolin-5-ylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	1.7000	uM
ethyl N-[5-[3-(methanesulfonamido)-4-methylphenyl]-3-methyl-3aH-pyrazolo[4,3-b]pyridin-7-yl]carbamate	1770706: Binding affinity to human BPTF by isothermal titration calorimetry	kd	1.8000	uM
6-[1-[3-(dimethylamino)propyl]indol-6-yl]-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	2.1000	uM
methyl 3-[[1-[2-(4-fluoroanilino)pyrimidin-4-yl]pyrrolidin-3-yl]carbamoylamino]benzoate	1289210: Binding affinity to BPTF (unknown origin) by isothermal titration calorimetric analysis	kd	2.8000	uM
5-(4-aminoanilino)-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	3.2000	uM
4-chloro-2-methyl-5-(5,6,7,8-tetrahydronaphthalen-2-ylamino)pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	3.9000	uM
4-chloro-2-methyl-5-[[(3R)-pyrrolidin-3-yl]amino]pyridazin-3-one	1770708: Binding affinity to BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells by SPR analysis	kd	6.0000	uM
4-[(2-amino-4-hydroxy-5-methylphenyl)diazenyl]-N-pyridin-2-ylbenzenesulfonamide	1054708: Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	ki	6.0600	uM
5-(azepan-3-ylamino)-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	7.7000	uM
N-methyl-2-methylsulfonyl-6-phenylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	7.8000	uM
5-(azetidin-3-ylamino)-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	8.7000	uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, affects expression	9
trichostatin A	affects cotreatment, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	increases expression, increases phosphorylation	2
Dronabinol	increases expression	2
Tretinoin	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
bisphenol A	increases methylation	1
2-butenal	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

125 unique, capped per target: 123 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3089617	Binding	Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains. — *J Med Chem*
CHEMBL5723061	Functional	Affinity Biochemical interaction: (AlphaScreen) EUB0000233b BPTF	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5NA	PGPC1_73	Induced pluripotent stem cell	Female
CVCL_SF45	HAP1 BPTF (-) 1	Cancer cell line	Male
CVCL_SF46	HAP1 BPTF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BPTF across ~30M SureChEMBL compounds — explore on Sugi Predict.