CHD1L

Summary

CHD1L (chromodomain helicase DNA binding protein 1 like, HGNC:1916) is a protein-coding gene on chromosome 1q21.1, encoding ATP-dependent chromatin remodeler CHD1L (Q86WJ1). ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage.

This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers.

Source: NCBI Gene 9557 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital anomaly of kidney and urinary tract (Limited, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 392 total
• Phenotypes (HPO): 2
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1916
Approved symbol	CHD1L
Name	chromodomain helicase DNA binding protein 1 like
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ALC1
Ensembl gene	ENSG00000131778
Ensembl biotype	protein_coding
OMIM	613039
Entrez	9557

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 28 protein_coding, 23 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000361293, ENST00000369258, ENST00000369259, ENST00000431239, ENST00000467213, ENST00000469625, ENST00000485113, ENST00000488864, ENST00000492728, ENST00000622533, ENST00000650714, ENST00000650721, ENST00000650813, ENST00000650828, ENST00000651070, ENST00000651206, ENST00000651207, ENST00000651226, ENST00000651231, ENST00000651407, ENST00000651410, ENST00000651420, ENST00000651510, ENST00000651820, ENST00000652161, ENST00000652188, ENST00000652278, ENST00000652346, ENST00000652357, ENST00000652486, ENST00000652494, ENST00000652587, ENST00000652616, ENST00000866229, ENST00000866230, ENST00000866231, ENST00000866232, ENST00000866233, ENST00000866234, ENST00000866235, ENST00000866236, ENST00000917448, ENST00000917449, ENST00000917450, ENST00000917451, ENST00000917452, ENST00000917453, ENST00000917454, ENST00000917455, ENST00000917456, ENST00000917457, ENST00000949387, ENST00000949388, ENST00000949389, ENST00000949390

RefSeq mRNA: 21 — MANE Select: NM_004284 NM_001256336, NM_001256337, NM_001256338, NM_001348451, NM_001348452, NM_001348453, NM_001348454, NM_001348455, NM_001348456, NM_001348457, NM_001348458, NM_001348459, NM_001348460, NM_001348461, NM_001348462, NM_001348463, NM_001348464, NM_001348465, NM_001348466, NM_004284, NM_024568

CCDS: CCDS58021, CCDS91037, CCDS91038, CCDS927

Canonical transcript exons

ENST00000369258 — 23 exons

Exon	Start	End
ENSE00003459146	147280026	147280191
ENSE00003473884	147295431	147295762
ENSE00003478298	147264422	147264584
ENSE00003483457	147272171	147272281
ENSE00003487736	147286298	147286500
ENSE00003499213	147285324	147285487
ENSE00003500329	147291482	147291552
ENSE00003501399	147276104	147276257
ENSE00003528946	147293608	147293722
ENSE00003546589	147267426	147267518
ENSE00003571148	147254870	147254976
ENSE00003578005	147265932	147266087
ENSE00003633603	147268782	147268878
ENSE00003641269	147287635	147287733
ENSE00003645235	147256531	147256562
ENSE00003646745	147294409	147294517
ENSE00003654599	147259837	147259918
ENSE00003675201	147284351	147284499
ENSE00003686048	147275354	147275468
ENSE00003690388	147255813	147255927
ENSE00003694290	147270932	147271005
ENSE00003716905	147252623	147252735
ENSE00003728289	147242684	147242830

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 93.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.7946 / max 202.8563, expressed in 1814 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4975	21.7409	1814
4971	3.5352	1477
4976	0.0295	22
4977	0.0242	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.38	gold quality
cerebellar hemisphere	UBERON:0002245	91.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.76	gold quality
cerebellar cortex	UBERON:0002129	91.64	gold quality
right lobe of liver	UBERON:0001114	91.51	gold quality
adenohypophysis	UBERON:0002196	91.27	gold quality
ascending aorta	UBERON:0001496	91.08	gold quality
thoracic aorta	UBERON:0001515	90.96	gold quality
mucosa of transverse colon	UBERON:0004991	90.88	gold quality
granulocyte	CL:0000094	90.82	gold quality
cerebellum	UBERON:0002037	90.61	gold quality
spleen	UBERON:0002106	90.40	gold quality
descending thoracic aorta	UBERON:0002345	90.23	gold quality
ventricular zone	UBERON:0003053	90.22	gold quality
rectum	UBERON:0001052	90.19	gold quality
spinal cord	UBERON:0002240	89.98	gold quality
aorta	UBERON:0000947	89.57	gold quality
smooth muscle tissue	UBERON:0001135	89.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.36	gold quality
pituitary gland	UBERON:0000007	89.19	gold quality
right testis	UBERON:0004534	88.87	gold quality
left testis	UBERON:0004533	88.75	gold quality
body of uterus	UBERON:0009853	88.74	gold quality
tibial artery	UBERON:0007610	88.69	gold quality
upper lobe of left lung	UBERON:0008952	88.68	gold quality
monocyte	CL:0000576	88.67	gold quality
popliteal artery	UBERON:0002250	88.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.64	gold quality
vermiform appendix	UBERON:0001154	88.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting CHD1L, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6883-3P	97.97	67.35	643
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6861-5P	96.23	67.19	800
HSA-MIR-4524B-3P	95.52	64.12	964

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• ALC1 is the target oncogene within the chromosome 1q21 amplicon and plays a pivotal role in hepeatocellular carcinoma pathogenesis. (PMID:18023026)
• results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites (PMID:19661379)
• Alc1 is a chromatin remodeling enzyme activated by binding of its macrodomain to poly(ADP-ribosyl)ated Parp1. Alc1 is recruited to nucleosomes in vitro and to chromatin in cells when Parp1 catalyzes poly(ADP-ribose) synthesis at sites of DNA damage. (PMID:19666485)
• Poly(ADP-ribosyl)ation directs recruitment and activation of the ATP-dependent chromatin remodeler ALC1 (PMID:19666485)
• CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. (PMID:20335658)
• Overexpression of CHD1L was significantly associated with tumour microsatellite formation, advanced tumour stage, overall survival time of patients who received transarterial chemoembolisation treatment and chemoresistance in hepatocellular carcinoma. (PMID:21068133)
• 1q21.1 copy number variant (CNV) results in newly identified function such as decatenation (chromatid untangling) checkpoint (DCC) activation in the case of CHD1l/ALC1 in lymphoblast cell lines. (PMID:21824431)
• CHD1L/TCTP/Cdc25C/Cdk1 molecular pathway causes the malignant transformation of hepatocytes with the phenotypes of accelerated mitotic progression and the production of aneuploidy (PMID:21953552)
• Mutation in CHD1L is associated with congenital anomalies of the kidneys and urinary tract. (PMID:22146311)
• positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma. (PMID:23020525)
• data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of nucleotide excision repair through DDB2 stabilization and recruitment of the chromatin remodeler ALC1 (PMID:23045548)
• the model that PAR present on PARylated PARP1 acts as an allosteric effector of ALC1 nucleosome remodeling activity. (PMID:23132853)
• CHD1L is the target oncogene within the 1q21 amplicon and plays a pivotal role in colorectal carcinoma pathogenesis. (PMID:23746766)
• Data indicate that chromodomain helicase/ATPase DNA-binding protein 1-like (CHD1L) might be an diagnostic and prognostic marker for bladder cancer (BC) patients. (PMID:23807680)
• TRIM33 plays a role in PARP-dependent DNA damage response and regulates ALC1 activity by promoting its timely removal from sites of DNA damage. (PMID:23926104)
• These results indicated that CHD1L could serve as a prognostic marker for gastric cancer (PMID:24258459)
• CHD1L is now considered to be a novel independent biomarker for progression, prognosis and survival in several solid tumors. [Review] (PMID:24359616)
• Relative mRNA expression level of CHD1L was higher in breast cancer cell lines. (PMID:25153161)
• CHD1L is involved in the progression of glioma. (PMID:26162969)
• Overexpression of CHD1L is positively associated with tumor metastasis of lung adenocarcinoma, and might serve as a novel prognostic biomarker and potential therapeutic target for patients. (PMID:26360781)
• This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer. (PMID:26599012)
• CHD1L exerts its anti-apoptotic role through the apoptotic pathway involving caspase-9-caspase-3 apoptotic pathway in MM cells. In addition, we determined that CHD1L expression is increased when MM cells were adhered to fibronectin (FN) or bone marrow stromal cells (PMID:27258734)
• overexpression of CHD1L in embryonic cells upregulated the expression of ectoderm genes, especially PAX6 (PMID:28946814)
• ALC1 is a unique base excision repair factor that functions in a chromatin context, most likely as a chromatin-remodeling enzyme. (PMID:29149203)
• Upon DNA damage, binding of PARylated PARP1 by the macro domain induces a conformational change that relieves autoinhibitory interactions with the ATPase motor, which selectively activates ALC1 remodeling upon recruitment to sites of DNA damage. (PMID:29220652)
• NAD(+)-metabolite and nucleic acid poly-ADP-ribose triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation. (PMID:29220653)
• implies a previously unappreciated role for ALC1 in DNA replication, in which ALC1 may regulate replication-fork slowing at CPT-induced DNA-damage sites (PMID:29408941)
• CHD1L overexpression was associated with poor prognosis and advanced clinicopathological features, CHD1L may be a valuable biomarker for prognostication of cancer patients. (PMID:30024537)
• The data demonstrate that CHD1L could induce cisplatin resistance in non-small-cell lung cancer via c-Jun-ABCB1-NF-kappaB axis. (PMID:30718500)
• High CHD1L expression is associated with proliferation and metastasis of intrahepatic cholangiocarcinoma. (PMID:31173252)
• Results show that ALC1 facilitates DNA end resection and homologous recombination and, as a consequence, impairs NHEJ. This role is exerted by controlling CtIP expression and relies on the presence of a G4 structure in the 5’-UTR of the CtIP major mRNA isoform. (PMID:32392243)
• First-in-Class Inhibitors of Oncogenic CHD1L with Preclinical Activity against Colorectal Cancer. (PMID:32499299)
• CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2. (PMID:32922205)
• The Oncogenic Helicase ALC1 Regulates PARP Inhibitor Potency by Trapping PARP2 at DNA Breaks. (PMID:33275888)
• The chromatin remodeler ALC1 underlies resistance to PARP inhibitor treatment. (PMID:33355125)
• Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch. (PMID:33357431)
• ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells. (PMID:33462394)
• Effect of chromodomain helicase/ATPase DNA binding protein 1-like gene on the invasion and metastasis of tongue squamous cell carcinoma CAL27 cells. (PMID:33723941)
• The high expression of CHD1L and its clinical significance in human solid tumors: A meta-analysis. (PMID:33725840)
• Suppressing CHD1L reduces the proliferation and chemoresistance in osteosarcoma. (PMID:33813077)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chd1l	ENSDARG00000015471
mus_musculus	Chd1l	ENSMUSG00000028089
rattus_norvegicus	Chd1l	ENSRNOG00000017669

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

ATP-dependent chromatin remodeler CHD1L — Q86WJ1 (reviewed: Q86WJ1)

Alternative names: Amplified in liver cancer protein 1, Chromo domain-containing protein 1-like

All UniProt accessions (20): A0A087WTM4, A0A087WWW4, A0A087WZM7, A0A0A0MRH8, A0A0A0MSH9, A0A494C0B8, A0A494C0F0, A0A494C0J6, A0A494C0M4, A0A494C0Q0, A0A494C111, A0A494C179, A0A494C1F3, A0A494C1F7, A0A494C1H0, A0A494C1H1, A0A494C1I3, A0A494C1P7, A0A494C1S1, Q86WJ1

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage. Recruited to DNA damage sites through interaction with poly-ADP-ribose: specifically recognizes and binds histones that are poly-ADP-ribosylated on serine residues in response to DNA damage. Poly-ADP-ribose-binding activates the ATP-dependent chromatin remodeler activity, thereby regulating chromatin during DNA repair. Catalyzes nucleosome sliding away from DNA breaks in an ATP-dependent manner. Chromatin remodeling activity promotes PARP2 removal from chromatin.

Subunit / interactions. Interacts with nucleosomes; interacts with the acidic patch of histones. Interacts (via macro domain) with PARP1; interacts only when PARP1 is poly-ADP-ribosylated (PARylated). Interacts with CIAO1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Frequently overexpressed in hepatomacellular carcinomas.

Activity regulation. Adopts an inactive conformation in absence of DNA damage. Binding to poly-ADP-ribosylated histones activates the ATP-dependent chromatin remodeler activity.

Domain organisation. The macro domain mediates non-covalent poly(ADP-ribose)-binding and recruitment to DNA damage sites. Mediates auto-inhibition of ATPase activity by interacting with the N-terminal ATPase module, encompassing the helicase ATP-binding domain and helicase C-terminal domain. Binding to poly-ADP-ribosylated histones upon DNA damage releases the auto-inhibition by the macro domain and trigger ATPase activity. Does not bind monomeric ADP-ribose and mono-ADP-ribose fails to release the auto-inhibition of the ATPase module by the macro domain.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q86WJ1-1	1	yes
Q86WJ1-2	2
Q86WJ1-3	3
Q86WJ1-4	4
Q86WJ1-5	5

RefSeq proteins (21): NP_001243265, NP_001243266, NP_001243267, NP_001335380, NP_001335381, NP_001335382, NP_001335383, NP_001335384, NP_001335385, NP_001335386, NP_001335387, NP_001335388, NP_001335389, NP_001335390, NP_001335391, NP_001335392, NP_001335393, NP_001335394, NP_001335395, NP_004275, NP_078844 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR002589	Macro_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031053	ALC1	Family
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR043472	Macro_dom-like	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain

Pfam: PF00176, PF00271

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (130 total): helix 36, strand 24, mutagenesis site 18, turn 13, sequence variant 9, modified residue 7, sequence conflict 6, splice variant 4, region of interest 4, domain 3, compositionally biased region 2, chain 1, binding site 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6ZHX	ELECTRON MICROSCOPY	2.5
7ENN	ELECTRON MICROSCOPY	2.8
6ZHY	ELECTRON MICROSCOPY	3
8B0A	ELECTRON MICROSCOPY	3
7EPU	X-RAY DIFFRACTION	3.5
7OTQ	ELECTRON MICROSCOPY	4.8
9T4V	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WJ1-F1	73.81	0.11

Antibody-complex structures (SAbDab): 1 — 7EPU

Functional residue map

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

Ligand- & substrate-binding residues (1): 71–78

Post-translational modifications (7): 9, 540, 607, 618, 628, 636, 891

Mutagenesis-validated functional residues (18):

Position	Phenotype
77	abolishes atpase activity.
175	abrogates chromatin remodeling activity. prevents parp2 removal from chromatin.
307–308	reduces interaction of the macro domain with the n-terminal atpase module; when associated with e-398 and e-750.
319–320	reduces interaction of the macro domain with the n-terminal atpase module; when associated with e-407; e-422 and e-750.
332–337	reduces interaction of the macro domain with the n-terminal atpase module; when associated with e-750.
381	decreased interaction with nucleosomes.
398	reduces interaction of the macro domain with the n-terminal atpase module; when associated with e-307, e-308 and e-750.
407	reduces interaction of the macro domain with the n-terminal atpase module; when associated with e-319, e-320, e-422 and
420	does not reduce interaction of the macro domain with the n-terminal atpase module; when associated with e-750.
422	reduces interaction of the macro domain with the n-terminal atpase module; when associated with e-319, e-320, e-407 and
457	abolished atp-dependent chromatin remodeler activity.
611–612	strongly reduced interaction with the acidic patch of histones.
611	reduced interaction with histones.
614	reduced interaction with histones.
653–656	does not reduce interaction of the macro domain with the n-terminal atpase module; when associated with e-750.
723	strongly reduces poly(adp-ribose)-binding but not atpase activity.
750	disrupts interaction with parp1. abolishes the release from auto-inhibition through macro domain binding to the n-termin
857	loss of auto-inhibition, leading to constitutive atp-dependent chromatin remodeler activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER

MSigDB gene sets: 134 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, TAATAAT_MIR126, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_DNA_DAMAGE_RESPONSE, REACTOME_DNA_REPAIR, GOBP_CHROMATIN_REMODELING, DANG_BOUND_BY_MYC, MULLIGHAN_MLL_SIGNATURE_2_DN, PARENT_MTOR_SIGNALING_UP, GOMF_CHROMATIN_BINDING, chr1q21, MARSON_BOUND_BY_FOXP3_STIMULATED, BENPORATH_MYC_MAX_TARGETS

GO Biological Process (3): DNA repair (GO:0006281), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974)

GO Molecular Function (10): nucleotide binding (GO:0000166), DNA helicase activity (GO:0003678), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleosome binding (GO:0031491), histone reader activity (GO:0140566), ATP-dependent chromatin remodeler activity (GO:0140658), poly-ADP-D-ribose modification-dependent protein binding (GO:0160004), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), site of double-strand break (GO:0035861), site of DNA damage (GO:0090734), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity, acting on DNA	2
cellular anatomical structure	2
DNA metabolic process	1
DNA damage response	1
chromatin organization	1
cellular response to stress	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
helicase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
chromatin binding	1
protein-containing complex binding	1
nucleosome	1
histone binding	1
chromatin-protein adaptor activity	1
DNA binding	1
chromatin remodeling	1
ADP-D-ribose modification-dependent protein binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
site of DNA damage	1
chromosome	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHD1L	PRKAB2	O43741	719
CHD1L	PARP1	P09874	717
CHD1L	ACP6	Q9NPH0	686
CHD1L	FMO5	P49326	658
CHD1L	GJA8	P48165	651
CHD1L	GJA5	P36382	641
CHD1L	NBPF11	Q86T75	581
CHD1L	ARHGEF9	O43307	570
CHD1L	CCNE1	P24864	533
CHD1L	GPHRA	B7ZAQ6	530
CHD1L	PARG	Q86W56	527
CHD1L	CDC42	P21181	524
CHD1L	BCL9	O00512	516
CHD1L	SPOCK1	Q08629	496
CHD1L	PARP2	Q9UGN5	492

IntAct

85 interactions, top by confidence:

A	B	Type	Score
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
INSYN2A	CHUK	psi-mi:“MI:0914”(association)	0.530
CCL22	PLXNA2	psi-mi:“MI:0914”(association)	0.530
CHD1L	TNKS	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
CHD1L	AKT1	psi-mi:“MI:2364”(proximity)	0.470
CHD1L	BRAF	psi-mi:“MI:2364”(proximity)	0.470
AKT1	CHD1L	psi-mi:“MI:0915”(physical association)	0.470
BRAF	CHD1L	psi-mi:“MI:0915”(physical association)	0.470
	CHD1L	psi-mi:“MI:0407”(direct interaction)	0.440
CHD1L	UBE2O	psi-mi:“MI:0915”(physical association)	0.370
NR4A1	CHD1L	psi-mi:“MI:0915”(physical association)	0.370
SCYL1	CHD1L	psi-mi:“MI:0915”(physical association)	0.370
CTCF	CHD1L	psi-mi:“MI:0915”(physical association)	0.370
SGO1	ELOC	psi-mi:“MI:0914”(association)	0.350
RETREG2	SLC27A2	psi-mi:“MI:0914”(association)	0.350
Osgep	RPSA	psi-mi:“MI:0914”(association)	0.350
ID1	TCF3	psi-mi:“MI:0914”(association)	0.350
LRRK2	TK1	psi-mi:“MI:0914”(association)	0.350
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXB1	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
FOXP1	MYL12B	psi-mi:“MI:0914”(association)	0.350

BioGRID (173): CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Affinity Capture-MS), CHD1L (Proximity Label-MS), CHD1L (Biochemical Activity), CHD1L (Affinity Capture-MS)

ESM2 similar proteins: A0A023PXF5, A6QSQ0, A6SBT4, A7EY76, F1RCY6, O13559, O18475, O48534, P18708, P40105, P40434, P40889, P43538, P46063, P46459, P46460, P46461, P54351, Q14527, Q1EB85, Q2TBP1, Q2U587, Q3B7N1, Q3E7Y4, Q5R410, Q5RF63, Q6AYJ1, Q6PCN7, Q7ZU90, Q86WJ1, Q8NHQ9, Q8R5F7, Q95216, Q96C10, Q99J87, Q9BYX4, Q9CXF7, Q9DGP9, Q9EPU0, Q9FF61

Diamond homologs: A0A0P0WGX7, A2A8L1, A2BGR3, A3KFM7, A6QQR4, A7Z019, A9X4T1, B0R0I6, B0XPE7, B3NAN8, B4GS98, B5BT18, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, F1Q8K0, F4I2H2, F4IV45, F4J9M5, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EF53, O12944, O13682, O14139, O14646, O14981, O43065, O76460, P0CO16, P0CO17, P28370, P31380, P32333

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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
Regulation of PD-L1(CD274) transcription	6	9.2×	9e-03
Ub-specific processing proteases	8	6.0×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	16.5×	4e-03
double-strand break repair	7	16.1×	3e-04
epidermal growth factor receptor signaling pathway	5	14.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	236
Likely benign	28
Benign	85

Top pathogenic / likely-pathogenic (0)

SpliceAI

3472 predictions. Top by Δscore:

Variant	Effect	Δscore
1:147265931:GCAA:G	acceptor_gain	1.0000
1:147268851:A:G	donor_gain	1.0000
1:147275343:A:AG	acceptor_gain	1.0000
1:147275343:ATT:A	acceptor_gain	1.0000
1:147275344:T:G	acceptor_gain	1.0000
1:147275345:T:A	acceptor_gain	1.0000
1:147275351:CAG:C	acceptor_loss	1.0000
1:147275352:A:AG	acceptor_gain	1.0000
1:147275352:AGGT:A	acceptor_gain	1.0000
1:147275352:AGGTG:A	acceptor_gain	1.0000
1:147275353:G:GG	acceptor_gain	1.0000
1:147275353:GGT:G	acceptor_gain	1.0000
1:147275353:GGTG:G	acceptor_gain	1.0000
1:147275353:GGTGG:G	acceptor_gain	1.0000
1:147275464:AACAA:A	donor_gain	1.0000
1:147275465:ACAA:A	donor_gain	1.0000
1:147275466:CAA:C	donor_gain	1.0000
1:147275467:AA:A	donor_gain	1.0000
1:147275469:G:C	donor_loss	1.0000
1:147275469:G:GG	donor_gain	1.0000
1:147276099:TCCAG:T	acceptor_loss	1.0000
1:147276100:CCA:C	acceptor_loss	1.0000
1:147276102:AGG:A	acceptor_loss	1.0000
1:147276103:G:A	acceptor_loss	1.0000
1:147276103:GGTCT:G	acceptor_gain	1.0000
1:147284342:T:G	acceptor_gain	1.0000
1:147284349:A:AG	acceptor_gain	1.0000
1:147284350:G:GG	acceptor_gain	1.0000
1:147284350:GA:G	acceptor_gain	1.0000
1:147284350:GAA:G	acceptor_gain	1.0000

AlphaMissense

5867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:147272269:A:C	S420R	0.998
1:147272271:T:A	S420R	0.998
1:147272271:T:G	S420R	0.998
1:147267483:T:C	L318P	0.997
1:147268829:A:C	S346R	0.997
1:147268831:T:A	S346R	0.997
1:147268831:T:G	S346R	0.997
1:147272217:A:C	R402S	0.997
1:147272217:A:T	R402S	0.997
1:147294415:T:A	V838D	0.997
1:147294421:T:C	L840P	0.997
1:147272185:C:A	R392S	0.996
1:147272186:G:C	R392P	0.996
1:147254957:T:A	W110R	0.995
1:147254957:T:C	W110R	0.995
1:147259866:A:T	E175V	0.995
1:147272216:G:C	R402T	0.995
1:147267486:G:C	R319P	0.994
1:147270951:T:C	F369L	0.994
1:147270953:C:A	F369L	0.994
1:147270953:C:G	F369L	0.994
1:147272197:T:C	S396P	0.994
1:147259844:T:A	W168R	0.993
1:147259844:T:C	W168R	0.993
1:147259881:A:T	K180I	0.993
1:147267491:T:C	C321R	0.993
1:147272236:T:C	F409L	0.993
1:147272238:T:A	F409L	0.993
1:147272238:T:G	F409L	0.993
1:147272264:T:C	L418P	0.993

dbSNP variants (sampled 300 via entrez): RS1000024721 (1:147270003 T>C), RS1000027603 (1:147195799 C>G), RS1000030214 (1:147228134 T>C), RS1000063445 (1:147241588 C>G,T), RS1000124995 (1:147275993 C>A,T), RS1000169204 (1:147200794 A>G), RS1000243252 (1:147290339 C>G), RS1000278263 (1:147252193 T>A), RS1000336950 (1:147214706 C>T), RS1000353163 (1:147270290 G>C), RS1000389533 (1:147214387 G>T), RS1000393777 (1:147171624 C>A), RS1000442268 (1:147171903 G>A,T), RS1000489353 (1:147227919 C>A), RS1000496051 (1:147274517 C>T)

Disease associations

OMIM: gene MIM:613039 | disease phenotypes: MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital anomaly of kidney and urinary tract	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital anomaly of kidney and urinary tract	Limited	AD

Mondo (4): neutropenia (MONDO:0001475), lymphopenia (MONDO:0003783), congenital anomaly of kidney and urinary tract (MONDO:0019719), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): Renal or urinary tract malformation (Orphanet:93545), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000189_35	Protein quantitative trait loci	2.000000e-07
GCST000189_7	Protein quantitative trait loci	7.000000e-07
GCST002806_16	Type 2 diabetes	6.000000e-06
GCST008839_10	Height	4.000000e-12
GCST012489_42	Heel bone mineral density x serum urate levels interaction	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004819	resistin measurement
EFO:0004509	hemoglobin measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008231	Lymphopenia	C15.378.243.750.605; C15.378.553.546.605; C20.673.627
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724766 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7541245	CHD1L, FMO5	3	2.75	1	metformin

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.52	IC50	3000	nM	CHEMBL1488758
5.52	IC50	3020	nM	CHEMBL1488758
5.17	IC50	6800	nM	CHEMBL1488758
5.12	IC50	7586	nM	CHEMBL1488758

PubChem BioAssay actives

4 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
6-[(3-methoxycarbonyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-2-yl)carbamoyl]cyclohex-3-ene-1-carboxylic acid	2104378: Inhibition of ALC1 (unknown origin) by FRET assay	ic50	3.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, increases expression	2
Formaldehyde	decreases expression	2
Cyclosporine	decreases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Vincristine	increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5547221	Binding	Inhibition of ALC1 (unknown origin) by FRET assay	Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and Repress Coronavirus Replication, Validating Mac1 as an Antiviral Target. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8IW	Ubigene HCT 116 CHD1L KO	Cancer cell line	Male
CVCL_SI87	HAP1 CHD1L (-) 1	Cancer cell line	Male
CVCL_SI88	HAP1 CHD1L (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%
NCT02643420	PHASE3	COMPLETED	SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)