CHAF1B

Summary

CHAF1B (chromatin assembly factor 1 subunit B, HGNC:1911) is a protein-coding gene on chromosome 21q22.12-q22.13, encoding Chromatin assembly factor 1 subunit B (Q13112). Acts as a component of the histone chaperone complex chromatin assembly factor 1 (CAF-1), which assembles histone octamers onto DNA during replication and repair. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Chromatin assembly factor I (CAF-I) is required for the assembly of histone octamers onto newly-replicated DNA. CAF-I is composed of three protein subunits, p50, p60, and p150. The protein encoded by this gene corresponds to the p60 subunit and is required for chromatin assembly after replication. The encoded protein is differentially phosphorylated in a cell cycle-dependent manner. In addition, it is normally found in the nucleus except during mitosis, when it is released into the cytoplasm. This protein is a member of the WD-repeat HIR1 family and may also be involved in DNA repair.

Source: NCBI Gene 8208 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 88 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1911
Approved symbol	CHAF1B
Name	chromatin assembly factor 1 subunit B
Location	21q22.12-q22.13
Locus type	gene with protein product
Status	Approved
Aliases	CAF1P60, CAF-1, CAF1, CAF1A, MPP7, MPHOSPH7
Ensembl gene	ENSG00000159259
Ensembl biotype	protein_coding
OMIM	601245
Entrez	8208

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000314103, ENST00000480486, ENST00000481458, ENST00000878604, ENST00000878605, ENST00000878606, ENST00000878607, ENST00000878608, ENST00000937265, ENST00000937266, ENST00000937267, ENST00000937268, ENST00000937269, ENST00000937270, ENST00000937271, ENST00000937272, ENST00000951948

RefSeq mRNA: 1 — MANE Select: NM_005441 NM_005441

CCDS: CCDS13644

Canonical transcript exons

ENST00000314103 — 14 exons

Exon	Start	End
ENSE00001044343	36415295	36415389
ENSE00001044347	36399521	36399605
ENSE00001044354	36409374	36409465
ENSE00001044359	36412884	36413315
ENSE00001044360	36408761	36408830
ENSE00001213718	36416275	36419015
ENSE00001384227	36385392	36385451
ENSE00003477571	36386060	36386262
ENSE00003480180	36394547	36394650
ENSE00003494204	36402758	36402851
ENSE00003561304	36411463	36411604
ENSE00003583414	36391551	36391668
ENSE00003613324	36387598	36387730
ENSE00003672161	36397415	36397511

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 88.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6109 / max 93.2690, expressed in 1431 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188992	7.6109	1431

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.78	gold quality
oocyte	CL:0000023	88.05	gold quality
gastrocnemius	UBERON:0001388	82.49	gold quality
muscle of leg	UBERON:0001383	82.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.07	gold quality
ventricular zone	UBERON:0003053	80.40	gold quality
skeletal muscle organ	UBERON:0014892	80.01	gold quality
muscle organ	UBERON:0001630	80.00	gold quality
ganglionic eminence	UBERON:0004023	79.11	gold quality
buccal mucosa cell	CL:0002336	78.99	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.85	gold quality
embryo	UBERON:0000922	77.63	gold quality
stromal cell of endometrium	CL:0002255	77.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.78	gold quality
sperm	CL:0000019	75.23	gold quality
skeletal muscle tissue	UBERON:0001134	74.20	gold quality
cartilage tissue	UBERON:0002418	73.96	silver quality
male germ cell	CL:0000015	73.80	gold quality
islet of Langerhans	UBERON:0000006	71.82	gold quality
cerebellar hemisphere	UBERON:0002245	71.21	gold quality
muscle tissue	UBERON:0002385	71.21	gold quality
cerebellar cortex	UBERON:0002129	71.19	gold quality
parotid gland	UBERON:0001831	71.00	gold quality
bone marrow	UBERON:0002371	70.75	gold quality
minor salivary gland	UBERON:0001830	70.70	gold quality
mucosa of transverse colon	UBERON:0004991	70.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.43	gold quality
cerebellum	UBERON:0002037	70.21	gold quality
pancreas	UBERON:0001264	70.16	gold quality
saliva-secreting gland	UBERON:0001044	70.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MGMT	Repression

miRNA regulators (miRDB)

17 targeting CHAF1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-424-3P	97.20	65.86	385
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-10A-3P	93.57	64.43	451

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• model is proposed in which the synergism between hAsf1 and CAF-1 for nucleosome formation during DNA repair is achieved through a transient physical interaction allowing histone delivery from Asf1 to CAF-1 [asf1(anti-silencing function 1)] (PMID:11897662)
• These data identify chromatin assembly factor 1 as an essential factor not only for S-phase-specific chromatin assembly but also for proliferating cell viability. (PMID:15024074)
• Downregulated protein level of CAF-1 p60 in adult brain of patients with Down syndrome (DS) in contrast to Alzheimer’s disease indicates that it can be considered specific for changes in DS. (PMID:15068244)
• The N- & C-terminal regions of ASF1a and ASF1b determine the different affinities of these two proteins for HIRA, by contacting regions outside the HIRA B domain. CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby competing with HIRA. (PMID:16980972)
• overexpression of CAF-1/p60 characterized prostatic cancers with a worse prognosis (PMID:19309489)
• The histone H3K9 methyltransferase SetDB1 associates with the specific heterochromatin protein 1alpha (HP1alpha)-chromatin assembly factor 1 (CAF1) chaperone complex. (PMID:19498464)
• Chromatin Assembly Factor-1/p60 may have a role in progression and metastasis of melanoma (PMID:20178651)
• CAF-1 is a proliferation marker in various malignant tumours with prognostic value in renal, endometrial and cervical carcinomas, which supports the value of CAF-1 as a clinical marker of cancer progression. (PMID:21083601)
• Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant salivary gland tumours with aggressive behaviour (PMID:21109952)
• All the evaluated malignant tumors showed CAF-1 p60 overexpression, confirming the emerging role of CAF-1 p60 as a new proliferation and prognostic marker for cancer. (PMID:23109837)
• The levels of the EDNRB, HJURP and p60/CAF-1 proteins were strongly associated with overall survival in high-grade gliomas patients (p<0.001, p<0.001 and p=0.002, respectively), whereas the one of PDLI4 was not (P=0.11). (PMID:24039914)
• The volumes of the tumors were similar between those injected with the empty vector and control, but were significantly smaller in the knockdown models, suggesting that the knockdown of the CHAF1B gene inhibited tumor growth. H&E staining revealed that tumors were developed in mice in all groups. (PMID:29767268)
• Study revealed that CHAF1B was highly expressed in nonsmall cell lung cancer (NSCLC) lung tissues and 95D cells. Survival analysis indicated that high CHAF1B expression in tumor tissue was associated with poor clinical outcomes in NSCLC patients. CHAF1B knockdown in 95D cells markedly inhibited tumor proliferation, reduced colony formation, induced cell cycle arrest and promoted apoptosis. (PMID:30720130)
• CHAF1A/B mediate silencing of unintegrated HIV-1 DNAs early in infection. (PMID:35074917)
• The histone H3/H4 chaperone CHAF1B prevents the mislocalization of CENP-A for chromosomal stability. (PMID:37129573)
• Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells. (PMID:37377894)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chaf1b	ENSDARG00000056473
mus_musculus	Chaf1b	ENSMUSG00000022945
rattus_norvegicus	Chaf1b	ENSRNOG00000001692
drosophila_melanogaster	Caf1-105	FBGN0033526
caenorhabditis_elegans	chaf-2	WBGENE00022141

Protein

Protein identifiers

Chromatin assembly factor 1 subunit B — Q13112 (reviewed: Q13112)

Alternative names: Chromatin assembly factor I p60 subunit, M-phase phosphoprotein 7

All UniProt accessions (1): Q13112

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the histone chaperone complex chromatin assembly factor 1 (CAF-1), which assembles histone octamers onto DNA during replication and repair. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer.

Subunit / interactions. Subunit of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A. CHAF1A binds directly to CHAF1B. Only minor amounts of RBBP4 are complexed with CHAF1A and CHAF1B in G1 phase. In G2 and S phase also monomeric CHAF1B is detected. Interacts with histones H3.1, H3.2 and H3.1t.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Differentially phosphorylated during cell cycle. During mitosis the p60 subunit of inactive CAF-1 is hyperphosphorylated and displaced into the cytosol. Progressivly dephosphorylated from G1 to S and G2 phase. Phosphorylated p60 is recruited to chromatin undergoing DNA repair after UV irradiation in G1, S or G2 phases.

Similarity. Belongs to the WD repeat HIR1 family.

RefSeq proteins (1): NP_005432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001632	WD40_G-protein_beta-like	Domain
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR029129	CAF1_p60_C	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045145	PTHR15271	Family
IPR055410	Beta-prop_CAF1B_HIR1	Domain

Pfam: PF15512, PF24105

UniProt features (63 total): strand 32, modified residue 12, repeat 7, compositionally biased region 4, turn 3, chain 1, sequence variant 1, sequence conflict 1, helix 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7Y5L	X-RAY DIFFRACTION	3.42
7Y5K	X-RAY DIFFRACTION	3.48
8IQG	ELECTRON MICROSCOPY	3.5
7Y5O	X-RAY DIFFRACTION	3.57
7Y5U	ELECTRON MICROSCOPY	3.8
7Y60	ELECTRON MICROSCOPY	3.8
8J6S	ELECTRON MICROSCOPY	3.8
8IQF	ELECTRON MICROSCOPY	4.6
7Y61	ELECTRON MICROSCOPY	5.6
7Y5V	ELECTRON MICROSCOPY	6.1
8J6T	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13112-F1	75.50	0.53

Functional residue map

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

Post-translational modifications (12): 394, 409, 419, 429, 433, 458, 494, 495, 509, 521, 531, 538

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 357 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, WHITEHURST_PACLITAXEL_SENSITIVITY, FISCHER_G1_S_CELL_CYCLE, GOBP_APICAL_JUNCTION_ASSEMBLY, KAUFFMANN_DNA_REPAIR_GENES, KONG_E2F3_TARGETS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, CEBALLOS_TARGETS_OF_TP53_AND_MYC_DN, FOSTER_TOLERANT_MACROPHAGE_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP

GO Biological Process (6): DNA replication (GO:0006260), DNA repair (GO:0006281), nucleosome assembly (GO:0006334), DNA replication-dependent chromatin assembly (GO:0006335), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (4): chromatin binding (GO:0003682), histone binding (GO:0042393), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), protein-containing complex (GO:0032991), CAF-1 complex (GO:0033186), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	2
chromatin organization	2
binding	2
DNA biosynthetic process	1
DNA damage response	1
nucleosome organization	1
protein-DNA complex assembly	1
cellular component organization	1
cellular response to stress	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cellular_component	1
protein-containing complex	1
cytoplasm	1

Protein interactions and networks

STRING

1618 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHAF1B	CHAF1A	Q13111	998
CHAF1B	RBBP4	P31149	975
CHAF1B	ASF1A	Q9Y294	803
CHAF1B	ASF1B	Q9NVP2	760
CHAF1B	H3C1	P02295	721
CHAF1B	H3-3A	P06351	696
CHAF1B	H3-4	Q16695	692
CHAF1B	H3-7	Q5TEC6	692
CHAF1B	H3-5	Q6NXT2	692
CHAF1B	H3C14	Q71DI3	691
CHAF1B	NASP	P49321	623
CHAF1B	RBBP7	Q16576	588
CHAF1B	SRSF1	Q07955	581
CHAF1B	POLA1	P09884	579
CHAF1B	MCM4	P33991	554

IntAct

99 interactions, top by confidence:

A	B	Type	Score
H3C1	CHAF1A	psi-mi:“MI:0914”(association)	0.910
CHAF1B	CHAF1A	psi-mi:“MI:0403”(colocalization)	0.870
CHAF1B	CHAF1A	psi-mi:“MI:0914”(association)	0.870
ASF1B	CHAF1B	psi-mi:“MI:0407”(direct interaction)	0.860
H3C1	RBBP4	psi-mi:“MI:0914”(association)	0.840
CHAF1B	RBBP4	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CHAF1B	CBX5	psi-mi:“MI:0914”(association)	0.790
CBX5	CHAF1A	psi-mi:“MI:0914”(association)	0.790
CHAF1A	CBX5	psi-mi:“MI:0914”(association)	0.790
CHAF1A	CBX5	psi-mi:“MI:0403”(colocalization)	0.790
H3C1	HAT1	psi-mi:“MI:0914”(association)	0.770
SMAD4	SMAD9	psi-mi:“MI:0914”(association)	0.750
H3C1	MCM2	psi-mi:“MI:0914”(association)	0.710
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
ASF1A	CHAF1B	psi-mi:“MI:0407”(direct interaction)	0.660
ASF1A	CHAF1B	psi-mi:“MI:0915”(physical association)	0.660
CEP72	AHCYL1	psi-mi:“MI:0914”(association)	0.640
ASF1A	HAT1	psi-mi:“MI:0914”(association)	0.640
CBX3	E2F6	psi-mi:“MI:0914”(association)	0.640
ASF1B	HAT1	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640

BioGRID (272): CHAF1B (Protein-peptide), CHAF1B (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), CHAF1B (Reconstituted Complex), CHAF1B (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), CHAF1A (Co-fractionation), CHAF1B (Co-fractionation), CHAF1B (Proximity Label-MS), CHAF1B (Affinity Capture-MS), CHAF1B (Co-purification), CHAF1B (Affinity Capture-MS), CHAF1B (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1TB62, A5D7H2, A7MB16, F1Q8X5, O14562, O35841, O42611, P0C606, P23116, P54198, P55884, P58405, P79987, Q13033, Q13112, Q14152, Q15542, Q1JU68, Q4G061, Q569Z1, Q5E9L7, Q5KU39, Q5R644, Q5R660, Q5R7U7, Q61666, Q676U5, Q6NYU2, Q6PCR7, Q8BHL5, Q8C092, Q8CBY8, Q8JZQ9, Q8QFR2, Q8VHE0, Q91W86, Q96ES7, Q96KG9, Q9BZZ5, Q9D0N7

Diamond homologs: A0JMQ0, A1CGS0, A1CQL6, A1D3I2, A2QHM1, A2QPW4, A3LVM1, A4R7U3, A5DXE2, A6RT32, A6ZYM0, A7EZJ5, A8IZG4, A8PWQ8, B0XQ15, B6H7A3, B8MWR8, B9WHJ2, G0SA60, O80990, P0CS38, P0CS39, P0CS46, P0CS47, P54198, P79987, Q05583, Q0CCS0, Q0CHM0, Q0USG2, Q13112, Q1DR81, Q1DZQ0, Q2GP45, Q2UG43, Q2UPI0, Q4WNK7, Q4WTL0, Q54KL5, Q5AEF2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHAF1B	“down-regulates quantity by repression”	MGMT	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	46.6×	3e-05
RHO GTPases activate PKNs	5	22.0×	3e-04
Gastrulation	5	18.0×	5e-04
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	6	12.7×	5e-04
Transcriptional and post-translational regulation of MITF-M expression and activity	5	12.4×	2e-03
SARS-CoV-1-host interactions	5	12.2×	2e-03
NuRD complex assembly	6	11.8×	7e-04
Regulation of PD-L1(CD274) transcription	7	10.6×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	11	18.4×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	61
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3248147	NC_000021.8:g.(?37707582)(38139606_?)del	Pathogenic
183350	NM_005441.3(CHAF1B):c.496A>G (p.Ile166Val)	Likely pathogenic

SpliceAI

6527 predictions. Top by Δscore:

Variant	Effect	Δscore
10:28056620:CTGT:C	acceptor_gain	1.0000
10:28059648:A:AC	donor_gain	1.0000
10:28059649:C:CC	donor_gain	1.0000
10:28069770:A:AC	donor_gain	1.0000
10:28069771:C:CC	donor_gain	1.0000
10:28069850:GACC:G	acceptor_loss	1.0000
10:28069853:C:CC	acceptor_gain	1.0000
10:28069854:T:C	acceptor_loss	1.0000
10:28089664:CACT:C	donor_loss	1.0000
10:28089665:ACTT:A	donor_loss	1.0000
10:28089666:CTTA:C	donor_loss	1.0000
10:28089667:TTAC:T	donor_loss	1.0000
10:28089668:TACC:T	donor_loss	1.0000
10:28089669:A:AC	donor_gain	1.0000
10:28089670:C:CC	donor_gain	1.0000
10:28089670:CCAA:C	donor_gain	1.0000
10:28089838:CCAG:C	acceptor_gain	1.0000
10:28089839:CAG:C	acceptor_gain	1.0000
10:28089839:CAGC:C	acceptor_gain	1.0000
10:28089840:AGC:A	acceptor_loss	1.0000
10:28089841:GC:G	acceptor_loss	1.0000
10:28089842:C:CC	acceptor_gain	1.0000
10:28089842:CTG:C	acceptor_loss	1.0000
10:28109807:C:CT	acceptor_gain	1.0000
10:28119649:A:AC	donor_gain	1.0000
10:28119650:C:CC	donor_gain	1.0000
10:28120590:TTAC:T	donor_loss	1.0000
10:28120591:TACC:T	donor_loss	1.0000
10:28120592:ACCTT:A	donor_loss	1.0000
10:28120593:C:CT	donor_loss	1.0000

AlphaMissense

3650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:36386164:T:A	W10R	1.000
21:36386164:T:C	W10R	1.000
21:36387677:T:A	V69D	1.000
21:36394635:T:A	W156R	1.000
21:36394635:T:C	W156R	1.000
21:36397454:T:A	V174D	1.000
21:36397511:G:T	R193M	1.000
21:36402806:C:A	R238S	1.000
21:36411603:T:A	W354R	1.000
21:36411603:T:C	W354R	1.000
21:36386166:G:C	W10C	0.999
21:36386166:G:T	W10C	0.999
21:36387601:T:A	W44R	0.999
21:36387601:T:C	W44R	0.999
21:36387681:T:A	N70K	0.999
21:36387681:T:G	N70K	0.999
21:36387719:C:G	S83W	0.999
21:36387727:G:C	D86H	0.999
21:36391568:T:A	W93R	0.999
21:36391568:T:C	W93R	0.999
21:36391646:T:A	W119R	0.999
21:36391646:T:C	W119R	0.999
21:36394560:G:C	D131H	0.999
21:36394578:T:A	W137R	0.999
21:36394578:T:C	W137R	0.999
21:36394611:T:C	S148P	0.999
21:36394612:C:A	S148Y	0.999
21:36394612:C:T	S148F	0.999
21:36394617:G:C	D150H	0.999
21:36394618:A:C	D150A	0.999

dbSNP variants (sampled 300 via entrez): RS1000101407 (21:36393472 A>G,T), RS1000293645 (21:36385800 G>C), RS1000437509 (21:36392163 A>G), RS1000592737 (21:36384785 T>A), RS1000625690 (21:36384399 T>A,C), RS1000665395 (21:36386190 C>T), RS1000698315 (21:36416637 A>G), RS1000775147 (21:36390778 C>T), RS1000787728 (21:36396455 A>G,T), RS1000828912 (21:36387227 T>TTG), RS1000944330 (21:36386857 C>T), RS1001385687 (21:36385706 C>G), RS1001592401 (21:36414313 G>A,T), RS1001782442 (21:36397182 T>G), RS1001815983 (21:36383978 A>G)

Disease associations

OMIM: gene MIM:601245 | disease phenotypes: MIM:253270

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Limited	Autosomal recessive

Mondo (4): prostate cancer (MONDO:0008315), intellectual disability (MONDO:0001071), attention deficit-hyperactivity disorder (MONDO:0007743), holocarboxylase synthetase deficiency (MONDO:0009666)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Holocarboxylase synthetase deficiency (Orphanet:79242), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002113_7	Pulmonary function	8.000000e-06
GCST005985_9	Creatinine levels	3.000000e-10
GCST008839_172	Height	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D028922	Holocarboxylase Synthetase Deficiency	C16.320.565.100.620.380; C16.320.565.202.720.380; C18.452.648.100.620.380; C18.452.648.202.720.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724753 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178891: Inhibition of CHAF1B (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
bisphenol A	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Cisplatin	decreases expression, increases expression	2
Dexamethasone	affects cotreatment, decreases expression	2
Methyl Methanesulfonate	decreases expression, increases expression	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
beta-glycerophosphoric acid	affects cotreatment, decreases expression	1
pinosylvin	decreases expression	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-hydroxy-equilenin	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697621	Binding	Inhibition of CHAF1B (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3K4	N/Tert-1 CHAF1B	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

497 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy