CHAF1A

Summary

CHAF1A (chromatin assembly factor 1 subunit A, HGNC:1910) is a protein-coding gene on chromosome 19p13.3, encoding Chromatin assembly factor 1 subunit A (Q13111). 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 99.7% of cancer cell lines).

Chromatin assembly factor I (CAF1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995 [PubMed 7600578]).

Source: NCBI Gene 10036 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 263 total — 1 pathogenic, 6 likely-pathogenic
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_005483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1910
Approved symbol	CHAF1A
Name	chromatin assembly factor 1 subunit A
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CAF1P150, CAF1B, CAF-1, CAF1, P150, MGC71229
Ensembl gene	ENSG00000167670
Ensembl biotype	protein_coding
OMIM	601246
Entrez	10036

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000301280, ENST00000585371, ENST00000585854, ENST00000587368, ENST00000587580, ENST00000587739, ENST00000589648, ENST00000900275, ENST00000900276, ENST00000900277, ENST00000926544, ENST00000926545, ENST00000926546, ENST00000926547, ENST00000926548, ENST00000926549, ENST00000926550

RefSeq mRNA: 1 — MANE Select: NM_005483 NM_005483

CCDS: CCDS32875

Canonical transcript exons

ENST00000301280 — 15 exons

Exon	Start	End
ENSE00001115452	4408903	4409759
ENSE00001115454	4429438	4429606
ENSE00001115457	4422566	4422795
ENSE00001115458	4418020	4418076
ENSE00001115459	4433070	4433539
ENSE00001115463	4429708	4429788
ENSE00001115464	4430549	4430641
ENSE00001207834	4442245	4442341
ENSE00001519531	4442925	4443397
ENSE00002279394	4402640	4402814
ENSE00003550753	4423335	4423395
ENSE00003563094	4423806	4423874
ENSE00003576078	4405912	4405962
ENSE00003640963	4428664	4428890
ENSE00003650648	4431952	4432207

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1166 / max 354.8353, expressed in 1669 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173340	11.9915	1647
173341	0.8048	480
173342	0.3202	177

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.58	gold quality
sural nerve	UBERON:0015488	93.57	gold quality
ventricular zone	UBERON:0003053	91.75	gold quality
oocyte	CL:0000023	90.04	gold quality
nipple	UBERON:0002030	88.56	gold quality
embryo	UBERON:0000922	88.28	gold quality
ganglionic eminence	UBERON:0004023	87.87	gold quality
gingival epithelium	UBERON:0001949	86.50	silver quality
tongue squamous epithelium	UBERON:0006919	86.31	silver quality
pylorus	UBERON:0001166	86.21	gold quality
amniotic fluid	UBERON:0000173	86.00	silver quality
endometrium epithelium	UBERON:0004811	85.75	gold quality
squamous epithelium	UBERON:0006914	85.47	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.44	silver quality
esophagus squamous epithelium	UBERON:0006920	85.23	silver quality
gingiva	UBERON:0001828	84.58	silver quality
epithelium of esophagus	UBERON:0001976	84.44	silver quality
bone marrow cell	CL:0002092	83.83	gold quality
cervix squamous epithelium	UBERON:0006922	83.73	silver quality
parotid gland	UBERON:0001831	83.71	silver quality
monocyte	CL:0000576	83.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.22	gold quality
triceps brachii	UBERON:0001509	83.16	silver quality
pharyngeal mucosa	UBERON:0000355	83.14	gold quality
thymus	UBERON:0002370	83.09	silver quality
mononuclear cell	CL:0000842	83.08	gold quality
endothelial cell	CL:0000115	83.06	gold quality
mucosa of transverse colon	UBERON:0004991	83.06	gold quality
gluteal muscle	UBERON:0002000	82.89	silver quality
bone marrow	UBERON:0002371	82.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.62
E-MTAB-6108	no	78.27

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MGMT	Repression

miRNA regulators (miRDB)

57 targeting CHAF1A, 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-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-26A-5P	99.78	73.52	2303

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 34)

• Altered mRNA expression is associated with prostate cancer recurrence. (PMID:15067324)
• p150 was efficiently phosphorylated by Cdc7-Dbf4 kinase. (PMID:16826239)
• ACF generates the characteristic 50- to 60-base-pair internucleosomal spacing in silent chromatin by kinetically discriminating against shorter linker DNAs (PMID:17099699)
• rs9352 of CHAF1A was repeatedly includes (78% of the 200 bootstrap samples) in the best set of SNPs. CHAF1A may contribute to gliomagenesis. (PMID:18559551)
• p150 directly activates transcription, independently of its histone deposition function. (PMID:19324875)
• Data show that human CAF-1 (p150) contains two PCNA interaction peptides, and suggest that these peptides are part of the mechanism that enables CAF-1 to function behind replication forks without interfering with other PCNA-mediated processes. (PMID:19822659)
• these findings suggest an expanded role of p150 as a SUMO2/3-interacting factor, and raise the intriguing possibility that p150 plays a role in promoting delivery of SUMO2/3 or SUMO2/3-modified proteins (or both) on chromatin fibers during replication. (PMID:19919826)
• CAF-I-dependent control of degradation of the discontinuous strands during mismatch repair. (PMID:21282622)
• CAF1 was hijacked by IE2 to facilitate the replication of the HCMV genome, suggesting chromatin assembly plays an important role in herpesviral DNA synthesis, but also provide a model of the virus-induced chromatin instability through CAF1. (PMID:21445097)
• Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma. (PMID:24335960)
• The frequency of positive CHAF1A staining in primary tumor mucosa (45.8% of 203 samples) was significantly elevated compared to normal mucosa (18.7% of samples). Increased expression was associated with cancer stage, tumor invasion and histological grade. (PMID:24845563)
• Novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus. (PMID:25057015)
• Taken together, these results show that CHAF1A contributes to the proliferation of glioblastoma cells and may be developed as a de novo drug target and prognosis biomarker of glioblastoma. (PMID:26740175)
• These data suggest that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers is compatible with MMR and protects the discontinuous daughter strand from unnecessary degradation by MMR machinery. (PMID:26945061)
• Chromatin reassembly during double-strand break repair was dependent on the HIRA histone chaperone that is specific to the replication-independent histone variant H3.3 and on CAF-1 that is specific to the replication-dependent canonical histones H3.1/H3.2. (PMID:27269284)
• CHAF1A inhibits NEIL1 initiated repair in vitro Subsequent restoration of the chaperone-BER complex in cell, presumably after completion of repair, suggests that histone chaperones sequester the repair complex for oxidized bases in non-replicating chromatin, and allow repair when oxidized bases are induced in the genome. (PMID:27794043)
• Loss of CAF1 is associated with increased motility and invasive phenotypes seen in transformed cells. (PMID:27872192)
• Data show that the high expression of chromatin assembly factor 1, subunit A (p150) (CHAF1A) promotes cell proliferation and inhibits cell apoptosis, suggesting that CHAF1A may be developed as a prognosis biomarker and potential therapeutic target of epithelial ovarian cancer (EOC). (PMID:28286267)
• Recent work has identified the chromatin assembly factor complex CAF-1 as a potent barrier to cellular reprogramming. In addition, CAF-1 has been implicated in the reversion of pluripotent cells to a totipotent-like state and in various lineage conversion paradigms, suggesting that modulation of CAF-1 levels may endow cells with a developmentally more plastic state. (PMID:28692904)
• CHAF1A and PCNA are highly expressed in cervical squamous cell carcinoma and associated with the malignancy (PMID:29382432)
• These and other approaches identified the Nucleosome Remodeling Deacetylase (NuRD) and Chromatin Assembly Factor 1 (CAF-1) complexes as necessary for DUX4 repression in human skeletal muscle cells and induced pluripotent stem (iPS) cells.Furthermore, DUX4-induced expression of MBD3L proteins partly relieved this repression in FSHD muscle cells. (PMID:29533181)
• this study identified a novel oncogenic role of CHAF1A in GC. The upregulation of CHAF1A can promote GC cell growth and predict poor prognosis in GC patients. (PMID:30449701)
• The histone chaperone Chromatin Assembly Factor 1 (CAF-1), which is recruited to DNA replication forks through its interaction with proliferating cell nuclear antigen (PCNA) for nucleosome assembly, participates in the establishment of H3K27me3-mediated silencing during differentiation. (PMID:31586391)
• Role of chromatin assembly factor-1/p60 and poly [ADP-ribose] polymerase 1 in mycosis fungoides. (PMID:33098490)
• Histone Loaders CAF1 and HIRA Restrict Epstein-Barr Virus B-Cell Lytic Reactivation. (PMID:33109754)
• CHAF1A overexpression in human retinoblastoma promotes cell proliferation and suppresses apoptosis. (PMID:33277876)
• Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer. (PMID:33785812)
• Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors. (PMID:34237585)
• CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming. (PMID:34365742)
• DNA methylation mediated downregulation of histone H3 variant H3.3 affects cell proliferation contributing to the development of HCC. (PMID:34626773)
• CHAF1A/B mediate silencing of unintegrated HIV-1 DNAs early in infection. (PMID:35074917)
• Aberrant SPOP-CHAF1A ubiquitination axis triggers tumor autophagy that endows a therapeutical vulnerability in diffuse large B cell lymphoma. (PMID:35773729)
• Unorthodox PCNA Binding by Chromatin Assembly Factor 1. (PMID:36232396)
• Inhibition of CAF-1 histone chaperone complex triggers cytosolic DNA and dsRNA sensing pathways and induces intrinsic immunity of hepatocellular carcinoma. (PMID:38051950)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chaf1a	ENSDARG00000062152
mus_musculus	Chaf1a	ENSMUSG00000002835
rattus_norvegicus	Chaf1a	ENSRNOG00000046479
caenorhabditis_elegans	chaf-1	WBGENE00011532

Protein

Protein identifiers

Chromatin assembly factor 1 subunit A — Q13111 (reviewed: Q13111)

Alternative names: Chromatin assembly factor I p150 subunit

All UniProt accessions (5): Q13111, K7EJF1, K7EME9, K7ENC7, K7EPA1

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. It may play a role in heterochromatin maintenance in proliferating cells by bringing newly synthesized cbx proteins to heterochromatic DNA replication foci.

Subunit / interactions. Homodimer. Part 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. Interacts with PCNA; the interaction is direct. Interacts (via the PxVxL motif) with CBX5; the interaction is direct. Interacts with MBD1. Interacts with histones H3.1, H3.2 and H3.1t.

Subcellular location. Nucleus.

Domain organisation. Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.

Similarity. Belongs to the CHAF1A family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13111-1	1	yes
Q13111-2	2
Q13111-3	3

RefSeq proteins (1): NP_005474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021644	CAF-1_p150_acidic	Domain
IPR022043	CAF1A_DD	Domain
IPR029091	CAF1_p150_N	Domain
IPR029105	CAF1-p150_C2	Domain

Pfam: PF11600, PF12253, PF15539, PF15557

UniProt features (68 total): modified residue 16, region of interest 12, strand 9, compositionally biased region 8, helix 7, sequence variant 5, splice variant 3, cross-link 2, mutagenesis site 2, chain 1, short sequence motif 1, sequence conflict 1, turn 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-Q13111-F1	59.06	0.06

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 (18): 65, 123, 138, 141, 143, 206, 224, 310, 722, 772, 775, 803, 865, 868, 873, 951, 182, 182

Mutagenesis-validated functional residues (2):

Position	Phenotype
240	abolishes interaction with cbx5; when associated with e-242.
242	abolishes interaction with cbx5; when associated with e-240.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 216 (showing top): MORF_DNMT1, MODULE_52, FISCHER_G1_S_CELL_CYCLE, CROONQUIST_NRAS_SIGNALING_DN, MORF_RRM1, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, MORF_HDAC2, MODULE_16, KAUFFMANN_DNA_REPAIR_GENES, GOLDRATH_ANTIGEN_RESPONSE, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, MUELLER_PLURINET

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 (5): chromatin binding (GO:0003682), identical protein binding (GO:0042802), obsolete unfolded protein binding (GO:0051082), chromo shadow domain binding (GO:0070087), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), protein-containing complex (GO:0032991), CAF-1 complex (GO:0033186)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
protein domain specific binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
cellular_component	1
protein-containing complex	1

Protein interactions and networks

STRING

1838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHAF1A	CHAF1B	Q13112	998
CHAF1A	RBBP4	P31149	984
CHAF1A	CBX5	P45973	777
CHAF1A	H3C1	P02295	743
CHAF1A	H3-3A	P06351	724
CHAF1A	H3-4	Q16695	712
CHAF1A	H3-7	Q5TEC6	712
CHAF1A	H3-5	Q6NXT2	712
CHAF1A	H3C14	Q71DI3	712
CHAF1A	ASF1A	Q9Y294	688
CHAF1A	POLDIP3	Q9BY77	660
CHAF1A	HDAC2	Q92769	651
CHAF1A	CXXC1	Q9P0U4	646
CHAF1A	TRIM28	Q13263	616
CHAF1A	ASF1B	Q9NVP2	615

IntAct

171 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
H3C1	RBBP4	psi-mi:“MI:0914”(association)	0.840
CHAF1A	ASF1B	psi-mi:“MI:0403”(colocalization)	0.840
ASF1B	CHAF1A	psi-mi:“MI:0403”(colocalization)	0.840
CHAF1B	RBBP4	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CBX5	CHAF1A	psi-mi:“MI:0915”(physical 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
PCNA	CHAF1A	psi-mi:“MI:0915”(physical association)	0.730
CHAF1A	PCNA	psi-mi:“MI:0407”(direct interaction)	0.730
H3C1	MCM2	psi-mi:“MI:0914”(association)	0.710
PCNA	POLD1	psi-mi:“MI:0914”(association)	0.670
P4HA3	FAM171A2	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

BioGRID (350): BECN1 (Affinity Capture-Western), ATG14 (Affinity Capture-Western), CHAF1A (Two-hybrid), CHAF1A (Two-hybrid), CHAF1A (Protein-peptide), CHAF1A (Affinity Capture-MS), CHAF1A (Co-fractionation), CHAF1A (Co-fractionation), CHAF1A (Co-fractionation), CHAF1A (Proximity Label-MS), CHAF1A (Proximity Label-MS), CHAF1A (Affinity Capture-MS), CHAF1A (Co-purification), CHAF1A (Affinity Capture-MS), CHAF1A (Affinity Capture-MS)

ESM2 similar proteins: A0JMK9, A0JMT0, A2BIL7, A6QLA6, A8DZJ1, B2KF05, B7ZD04, O13024, O60237, O88379, O94880, P25992, P53352, Q09228, Q0IHP2, Q12495, Q12830, Q13111, Q1LVC2, Q1MTN9, Q24595, Q2PE14, Q32N93, Q3T8J9, Q52KF3, Q535K8, Q5R1T0, Q6DD45, Q6ZRS2, Q7K3L1, Q7KW09, Q7T308, Q801E2, Q803U7, Q86BP6, Q8BG95, Q8K298, Q98TA5, Q99PI5, Q9D4H9

Diamond homologs: A0JMK9, A0JMT0, A6QLA6, B2ZX90, Q13111, Q5R1T0, Q98TA5, Q9QWF0, Q9SXY0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHAF1A	“down-regulates quantity by repression”	MGMT	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	40.0×	2e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	40.0×	2e-05
CD28 dependent PI3K/Akt signaling	5	23.4×	1e-04
RHO GTPases activate PKNs	6	22.7×	3e-05
Transcriptional Regulation by E2F6	5	17.4×	2e-04
ChAHP complex assembly	6	13.2×	2e-04
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	7	12.7×	1e-04
SARS-CoV-1-host interactions	6	12.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	13	17.4×	4e-10
G1/S transition of mitotic cell cycle	6	11.5×	1e-03
DNA replication	7	11.0×	7e-04
chromatin remodeling	9	6.2×	1e-03
DNA repair	9	5.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	6
Uncertain significance	209
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4710569	NM_005483.3(CHAF1A):c.2004G>A (p.Trp668Ter)	Pathogenic
3242435	NM_005483.3(CHAF1A):c.1604+1G>A	Likely pathogenic
3242436	NM_005483.3(CHAF1A):c.1689_1690del (p.Cys563_Glu564delinsTer)	Likely pathogenic
3242437	NM_005483.3(CHAF1A):c.876del (p.Thr293fs)	Likely pathogenic
3242438	NM_005483.3(CHAF1A):c.1377+1G>A	Likely pathogenic
3242439	NM_005483.3(CHAF1A):c.621_630dup (p.Thr211fs)	Likely pathogenic
3242440	NM_005483.3(CHAF1A):c.2069G>A (p.Trp690Ter)	Likely pathogenic

SpliceAI

3013 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4402802:G:T	donor_gain	1.0000
19:4402810:CACAG:C	donor_loss	1.0000
19:4402813:AG:A	donor_loss	1.0000
19:4402815:G:A	donor_loss	1.0000
19:4408901:A:AG	acceptor_gain	1.0000
19:4408902:G:GG	acceptor_gain	1.0000
19:4408902:GCCC:G	acceptor_gain	1.0000
19:4418075:GA:G	donor_gain	1.0000
19:4418077:G:GG	donor_gain	1.0000
19:4422761:G:GT	donor_gain	1.0000
19:4422777:A:T	donor_gain	1.0000
19:4422785:G:GT	donor_gain	1.0000
19:4422791:CTGGA:C	donor_gain	1.0000
19:4422793:GGA:G	donor_gain	1.0000
19:4422794:GA:G	donor_gain	1.0000
19:4422794:GAG:G	donor_gain	1.0000
19:4422796:G:GG	donor_gain	1.0000
19:4423784:T:G	acceptor_gain	1.0000
19:4423871:CAAG:C	donor_loss	1.0000
19:4423873:AGGT:A	donor_loss	1.0000
19:4423875:G:GA	donor_loss	1.0000
19:4423876:T:G	donor_loss	1.0000
19:4428662:A:AG	acceptor_gain	1.0000
19:4428663:G:GA	acceptor_gain	1.0000
19:4428663:GA:G	acceptor_gain	1.0000
19:4428663:GACC:G	acceptor_gain	1.0000
19:4428888:CAGGT:C	donor_loss	1.0000
19:4428890:GGT:G	donor_loss	1.0000
19:4428891:G:GA	donor_loss	1.0000
19:4429433:CTCA:C	acceptor_loss	1.0000

AlphaMissense

6328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4429744:T:A	W604R	1.000
19:4429744:T:C	W604R	1.000
19:4433100:G:A	G745D	1.000
19:4433136:T:C	F757S	1.000
19:4433318:T:A	W818R	1.000
19:4433318:T:C	W818R	1.000
19:4429746:G:C	W604C	0.999
19:4429746:G:T	W604C	0.999
19:4430594:T:C	F634L	0.999
19:4430596:C:A	F634L	0.999
19:4430596:C:G	F634L	0.999
19:4432006:T:A	W668R	0.999
19:4432006:T:C	W668R	0.999
19:4433082:T:C	L739P	0.999
19:4433094:T:C	L743P	0.999
19:4433100:G:T	G745V	0.999
19:4433104:T:A	N746K	0.999
19:4433104:T:G	N746K	0.999
19:4433135:T:C	F757L	0.999
19:4433137:C:A	F757L	0.999
19:4433137:C:G	F757L	0.999
19:4433259:T:A	L798H	0.999
19:4433319:G:C	W818S	0.999
19:4433320:G:C	W818C	0.999
19:4433320:G:T	W818C	0.999
19:4433381:T:A	W839R	0.999
19:4433381:T:C	W839R	0.999
19:4428688:T:C	F468L	0.998
19:4428690:T:A	F468L	0.998
19:4428690:T:G	F468L	0.998

dbSNP variants (sampled 300 via entrez): RS1000017959 (19:4448271 G>A), RS1000034734 (19:4444649 T>C), RS1000039531 (19:4410696 T>C), RS1000047223 (19:4442358 A>T), RS1000061425 (19:4444059 C>T), RS1000064007 (19:4410411 C>T), RS1000106244 (19:4402378 G>A), RS1000111343 (19:4404564 A>C), RS1000116518 (19:4415462 C>T), RS1000141055 (19:4405366 T>G), RS1000147570 (19:4444820 C>A), RS1000236826 (19:4439456 C>T), RS1000261011 (19:4440467 G>A), RS1000317189 (19:4448149 C>T), RS1000406942 (19:4410172 G>C)

Disease associations

OMIM: gene MIM:601246 | disease phenotypes: MIM:164210

GenCC curated gene-disease

Mondo (2): craniofacial microsomia (MONDO:0015397), craniofacial microsomia 1 (MONDO:0958175)

Orphanet (3): Oculo-auriculo-vertebral spectrum (Orphanet:141132), Goldenhar syndrome (Orphanet:374), Otomandibular syndrome (Orphanet:141136)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004602_259	Mean corpuscular volume	2.000000e-72
GCST004621_205	Red cell distribution width	2.000000e-22
GCST004630_54	Mean corpuscular hemoglobin	1.000000e-63
GCST006804_38	Red cell distribution width	4.000000e-14
GCST90002384_444	Hemoglobin	4.000000e-14
GCST90002390_514	Mean corpuscular hemoglobin	2.000000e-102
GCST90002392_54	Mean corpuscular volume	2.000000e-145
GCST90002396_11	Mean reticulocyte volume	6.000000e-106
GCST90002397_176	Mean spheric corpuscular volume	6.000000e-165
GCST90002404_553	Red cell distribution width	2.000000e-30

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004509	hemoglobin measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006053	Goldenhar Syndrome	C05.116.099.370.231.576.410; C05.660.207.231.576.410; C16.131.621.207.231.576.410

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	decreases expression, increases expression	2
Copper	affects binding, decreases expression, increases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Thapsigargin	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
methylselenic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01674439	PHASE2	COMPLETED	Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells
NCT05610878	PHASE1	RECRUITING	Efficacy of Preconditioned Adipose-Derived Stem Cells in Fat Grafting
NCT02224677	Not specified	COMPLETED	Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK)
NCT02494752	Not specified	UNKNOWN	Role of Mesenchymal Stem Cells in Fat Grafting
NCT03806361	Not specified	COMPLETED	Fat Grafts With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children
NCT03861650	Not specified	COMPLETED	Evaluation of Effect of Bone Marrow Aspirate Concentrate on Distracted Mandibular Bone Properties
NCT03869021	Not specified	COMPLETED	Computer Guided for Mandibular Distraction Osteogenesis
NCT04056858	Not specified	COMPLETED	Study of a Candidate Gene Involved in Goldenhar Syndrome.
NCT04351893	Not specified	COMPLETED	Craniofacial Microsomia: Accelerating Understanding of the Significance and Etiology
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.