ERCC6L

Summary

ERCC6L (ERCC excision repair 6 like, spindle assembly checkpoint helicase, HGNC:20794) is a protein-coding gene on chromosome Xq13.1, encoding DNA excision repair protein ERCC-6-like (Q2NKX8). DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase. It is a selective cancer dependency (DepMap: 11.5% of cell lines).

This gene encodes a member of the SWItch/Sucrose Non-Fermentable (SWI/SNF2) family of proteins, and contains a SNF2-like ATPase domain and a PICH family domain. One distinguishing feature of this SWI/SNF protein family member is that during interphase, the protein is excluded from the nucleus, and only associates with chromatin after the nuclear envelope has broken down. This protein is a DNA translocase that is thought to bind double-stranded DNA that is exposed to stretching forces, such as those exerted by the mitotic spindle. This protein associates with ribosomal DNA and ultra-fine DNA bridges (UFBs), fine structures that connect sister chromatids during anaphase at some sites such as fragile sites, telomeres and centromeres. This gene is required for the faithful segregation of sister chromatids during mitosis, and the ATPase activity of this protein required for the resolution of UFBs before cytokinesis.

Source: NCBI Gene 54821 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 144 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 11.5% of screened cell lines
• MANE Select transcript: NM_017669

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20794
Approved symbol	ERCC6L
Name	ERCC excision repair 6 like, spindle assembly checkpoint helicase
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20105, PICH, RAD26L
Ensembl gene	ENSG00000186871
Ensembl biotype	protein_coding
OMIM	300687
Entrez	54821

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000334463, ENST00000373657

RefSeq mRNA: 2 — MANE Select: NM_017669 NM_001009954, NM_017669

CCDS: CCDS35329

Canonical transcript exons

ENST00000334463 — 2 exons

Exon	Start	End
ENSE00001610518	72238844	72239027
ENSE00003501613	72204665	72208698

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 83.59.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4319 / max 110.7990, expressed in 844 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199576	2.4319	844

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	83.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.36	gold quality
ventricular zone	UBERON:0003053	77.38	gold quality
oocyte	CL:0000023	74.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.46	gold quality
embryo	UBERON:0000922	73.22	gold quality
ganglionic eminence	UBERON:0004023	73.14	gold quality
stromal cell of endometrium	CL:0002255	68.85	gold quality
trabecular bone tissue	UBERON:0002483	67.87	silver quality
bone marrow	UBERON:0002371	66.59	gold quality
mucosa of transverse colon	UBERON:0004991	63.60	gold quality
esophagus squamous epithelium	UBERON:0006920	63.42	silver quality
vermiform appendix	UBERON:0001154	62.74	gold quality
rectum	UBERON:0001052	62.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	62.37	silver quality
lymph node	UBERON:0000029	62.01	gold quality
colonic mucosa	UBERON:0000317	61.70	gold quality
lower esophagus mucosa	UBERON:0035834	61.23	gold quality
esophagus mucosa	UBERON:0002469	60.46	gold quality
bone marrow cell	CL:0002092	60.39	gold quality
colonic epithelium	UBERON:0000397	60.09	gold quality
gingival epithelium	UBERON:0001949	60.02	silver quality
cartilage tissue	UBERON:0002418	59.73	silver quality
caecum	UBERON:0001153	59.13	gold quality
tonsil	UBERON:0002372	59.07	gold quality
epithelium of nasopharynx	UBERON:0001951	58.90	gold quality
gingiva	UBERON:0001828	58.33	silver quality
adrenal tissue	UBERON:0018303	57.86	gold quality
oral cavity	UBERON:0000167	56.54	silver quality
endometrium	UBERON:0001295	56.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting ERCC6L, 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-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-4633-5P	96.17	66.36	501
HSA-MIR-759	96.16	66.77	873

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 27)

• Functional characterization of the mouse Ercc6l ortholog. (PMID:15917148)
• These data identify PICH as a novel essential component of checkpoint signaling. (PMID:17218258)
• The sensitivity to depletion of topo IIalpha might be linked to structural alterations within the centromere domain, indicated by shortening of the distance across metaphase sister centromeres and persistence of PICH-coated connections. (PMID:17956945)
• PICH phosphorylation and its ATPase activity are required for mitotic chromosome compaction through the targeting of Plk1 to chromosome arms. (PMID:18418076)
• the spindle checkpoint failure formerly attributed to the depletion of PICH most likely reflects an off-target effect that causes the lowering of Mad2 transcript and protein. (PMID:19904549)
• the PICH-Plk1 complex plays a critical role in maintaining prometaphase chromosome architecture (PMID:20130082)
• PICH binds to BLM and enables BLM localization to anaphase centromeric threads. PICH and BLM unravel centromeric chromatin and keep anaphase DNA threads mostly free of nucleosomes. (PMID:21743438)
• PICH protein was required for the correct recruitment to the centromere of active topoisomerase IIalpha, an enzyme specialized in the catenation/decatenation process. (PMID:22563370)
• PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids. (PMID:23973328)
• PICH is a SUMO-interacting protein and a mitotic SUMO substrate. (PMID:25564610)
• PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis. (PMID:26643143)
• a novel SUMO-dependent regulation of PICH’s function on mitotic centromeres, is reported. (PMID:27230136)
• Characterization of the NTPR and BD1 interacting domains of the human PICH-BEND3 complex has been reported. (PMID:27487930)
• the mitotic roles of PICH and explore further the role of PICH in the timely segregation of the ribosomal DNA locus, are reported. (PMID:27565185)
• ERCC6L may stimulates cancer cell proliferation by promoting cell cycle through a way of RAB31-MAPK-CDK2, and it could be a potential biomarker for cancer prognosis and target for cancer treatment. (PMID:28178669)
• Data indicate BEND3 as a new interaction partner for PICH in mitosis, and have defined the residues within a TPR-BEN domain interface that mediate this interaction. (PMID:28977671)
• These findings suggested that ERCC6L, which is highly expressed in breast cancer, acts as an oncogene, is involved in breast cancer development and may serve as a novel molecular target for the treatment of breast cancer. (PMID:30066865)
• the present study provides preliminary evidence of the promoting effect of ERCC6L on the cell viability of RCC in vitro and in vivo. Further studies of the mechanisms underlying the regulation of ERCC6L may provide novel therapeutic targets in RCC. (PMID:30459398)
• The study shows the dependency of triple-negative breast cancer cells on PICH for faithful chromosome segregation. (PMID:31160555)
• Development and validation of hub genes for lymph node metastasis in patients with prostate cancer. (PMID:32130760)
• ERCC6L promotes the progression of hepatocellular carcinoma through activating PI3K/AKT and NF-kappaB signaling pathway. (PMID:32891122)
• The ZATT-TOP2A-PICH Axis Drives Extensive Replication Fork Reversal to Promote Genome Stability. (PMID:33296677)
• ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-kappaB signaling. (PMID:34425559)
• ERCC6L is a biomarker and therapeutic target for non-small cell lung adenocarcinoma. (PMID:35150321)
• Overexpression of ERCC6L correlates with poor prognosis and confers malignant phenotypes of lung adenocarcinoma. (PMID:35656882)
• A pan-cancer analysis of the oncogenic role of ERCC6L. (PMID:36550435)
• ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle. (PMID:37667329)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ercc6l	ENSDARG00000002479
mus_musculus	Ercc6l	ENSMUSG00000051220
rattus_norvegicus	Ercc6l	ENSRNOG00000003208

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), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

DNA excision repair protein ERCC-6-like — Q2NKX8 (reviewed: Q2NKX8)

Alternative names: ATP-dependent helicase ERCC6-like, PLK1-interacting checkpoint helicase, Tumor antigen BJ-HCC-15

All UniProt accessions (2): Q2NKX8, B5MDQ0

UniProt curated annotations — full annotation on UniProt →

Function. DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase. Functions as ATP-dependent DNA translocase. Can promote Holliday junction branch migration (in vitro).

Subunit / interactions. Interacts with PLK1, which phosphorylates it. Both proteins are mutually dependent on each other for correct subcellular localization. Interacts (via N-terminal TPR repeat) with BEND3 (via BEN domains 1 and 3); the interaction is direct.

Subcellular location. Chromosome. Centromere. Kinetochore.

Post-translational modifications. Phosphorylation by PLK1 prevents the association with chromosome arms and restricts its localization to the kinetochore-centromere region.

Similarity. Belongs to the SNF2/RAD54 helicase family.

RefSeq proteins (2): NP_001009954, NP_060139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001650	Helicase_C-like	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain
IPR050496	SNF2_RAD54_helicase_repair	Family

Pfam: PF00176, PF00271

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (47 total): modified residue 18, mutagenesis site 6, sequence conflict 5, compositionally biased region 4, region of interest 4, helix 3, repeat 2, domain 2, chain 1, binding site 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5JNO	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2NKX8-F1	62.93	0.16

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): 122–129

Post-translational modifications (18): 14, 755, 774, 807, 810, 813, 820, 969, 971, 995, 1004, 1028, 1063, 1069, 1098, 1118, 1181, 1188

Mutagenesis-validated functional residues (6):

Position	Phenotype
11	decreased affinity for bend3, and abolishes bend3-mediated stimulation of atpase activity; when associated with a-13 and
13	decreased affinity for bend3, and abolishes bend3-mediated stimulation of atpase activity; when associated with a-11 and
21	decreased affinity for bend3, and abolishes bend3-mediated stimulation of atpase activity; when associated with a-11 and
127–129	abolishes chromatin association.
128	abolishes atpase activity.
1063	induces a decrease in phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 189 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, WANG_CLIM2_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, KONG_E2F3_TARGETS, PID_PLK1_PATHWAY, GOBP_DNA_DAMAGE_RESPONSE, GARY_CD5_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, ROSTY_CERVICAL_CANCER_PROLIFERATION_CLUSTER, BIDUS_METASTASIS_UP, KOBAYASHI_EGFR_SIGNALING_24HR_DN, REACTOME_CELL_CYCLE_CHECKPOINTS, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (2): DNA repair (GO:0006281), cell division (GO:0051301)

GO Molecular Function (9): DNA binding (GO:0003677), DNA helicase activity (GO:0003678), ATP binding (GO:0005524), DNA translocase activity (GO:0015616), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): kinetochore (GO:0000776), cytosol (GO:0005829), membrane (GO:0016020), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity, acting on DNA	2
ATP-dependent activity	2
intracellular membraneless organelle	2
cellular anatomical structure	2
DNA metabolic process	1
DNA damage response	1
cellular process	1
nucleic acid binding	1
helicase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
DNA binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1
cytoplasm	1
chromosomal region	1

Protein interactions and networks

STRING

3034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERCC6L	PLK1	P53350	948
ERCC6L	RMI1	Q9H9A7	880
ERCC6L	TOP3A	Q13472	795
ERCC6L	MAD2L1	Q13257	774
ERCC6L	BLM	P54132	680
ERCC6L	CENPA	P49450	619
ERCC6L	CENPI	Q92674	618
ERCC6L	SKA1	Q96BD8	603
ERCC6L	TOP2A	P11388	593
ERCC6L	POLDIP3	Q9BY77	591
ERCC6L	CENPM	Q9NSP4	584
ERCC6L	WRN	Q14191	579
ERCC6L	CDK1	P06493	569
ERCC6L	CENPK	Q9BS16	562
ERCC6L	CDCA8	Q53HL2	559

IntAct

118 interactions, top by confidence:

A	B	Type	Score
PLK1	ERCC6L	psi-mi:“MI:0914”(association)	0.790
ERCC6L	PLK1	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HTT	ERCC6L	psi-mi:“MI:0915”(physical association)	0.700
ERCC6L	LMO4	psi-mi:“MI:0915”(physical association)	0.560
PWP2	ERCC6L	psi-mi:“MI:0915”(physical association)	0.560
ERCC6L	PWP2	psi-mi:“MI:0915”(physical association)	0.560
ERCC6L		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (120): ERCC6L (Two-hybrid), ERCC6L (Two-hybrid), ERCC6L (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), EIF4B (Affinity Capture-MS), LDHA (Affinity Capture-MS), PLK1 (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), PLK1 (Affinity Capture-MS), SIX1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JZ79, A1ZA92, A6QQR4, A7E2Z2, A8JQ65, A8WRG3, B3NYS4, B4K6T8, B4R0A5, B6VQ60, F4JZ68, O75164, O94640, P06700, P33294, P42124, P50526, P70351, Q04688, Q08BS4, Q14149, Q15910, Q21921, Q28D84, Q28Z18, Q2NKX8, Q4R381, Q4V863, Q5RD88, Q5RDS6, Q5RDX4, Q60L58, Q61188, Q61IS6, Q640I9, Q6DTM3, Q6PL18, Q757M7, Q8CDM1, Q8K3E5

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

2 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	ERCC6L	phosphorylation
PLK1	up-regulates	ERCC6L	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Apoptosis	5	10.5×	7e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	9.7×	7e-03
Programmed Cell Death	5	9.2×	8e-03
G2/M DNA damage checkpoint	6	9.0×	5e-03
RHO GTPase Effectors	8	6.8×	3e-03
Signaling by Rho GTPases	11	4.7×	3e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	11	4.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

391 predictions. Top by Δscore:

Variant	Effect	Δscore
X:72238841:TACCT:T	donor_loss	1.0000
X:72208694:CATAT:C	acceptor_gain	0.9900
X:72208696:TAT:T	acceptor_gain	0.9900
X:72208696:TATC:T	acceptor_loss	0.9900
X:72208697:AT:A	acceptor_gain	0.9900
X:72208699:C:CC	acceptor_gain	0.9900
X:72208699:C:T	acceptor_loss	0.9900
X:72208701:A:C	acceptor_gain	0.9900
X:72238842:A:AC	donor_gain	0.9900
X:72238843:C:CC	donor_gain	0.9900
X:72208695:ATAT:A	acceptor_gain	0.9800
X:72238842:AC:A	donor_gain	0.9800
X:72238843:CC:C	donor_gain	0.9800
X:72208701:A:AC	acceptor_gain	0.9700
X:72238843:CCT:C	donor_gain	0.9500
X:72238843:CCTTA:C	donor_gain	0.9300
X:72238843:CCTT:C	donor_gain	0.9100
X:72208462:T:TA	donor_gain	0.9000
X:72235912:G:C	acceptor_gain	0.9000
X:72235910:G:GC	acceptor_gain	0.8800
X:72235912:G:GC	acceptor_gain	0.8700
X:72221405:G:C	donor_gain	0.8600
X:72231154:A:T	acceptor_gain	0.8600
X:72238874:AAGG:A	donor_gain	0.8400
X:72221197:T:TA	donor_gain	0.8100
X:72235910:G:C	acceptor_gain	0.7900
X:72208695:ATATC:A	acceptor_gain	0.7700
X:72208696:TATCT:T	acceptor_gain	0.7700
X:72208697:ATCTA:A	acceptor_gain	0.7700
X:72208698:TCTAT:T	acceptor_gain	0.7700

AlphaMissense

8293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:72207095:A:G	W558R	0.999
X:72207095:A:T	W558R	0.999
X:72207659:A:G	W370R	0.998
X:72207659:A:T	W370R	0.998
X:72208103:A:G	W222R	0.998
X:72208103:A:T	W222R	0.998
X:72206842:A:G	L642P	0.997
X:72208081:T:A	E229V	0.997
X:72208289:A:G	W160R	0.997
X:72208289:A:T	W160R	0.997
X:72206992:T:A	E592V	0.996
X:72207080:C:G	D563H	0.996
X:72207899:A:C	Y290D	0.996
X:72207909:A:C	F286L	0.996
X:72207909:A:T	F286L	0.996
X:72207910:A:G	F286S	0.996
X:72207911:A:G	F286L	0.996
X:72208078:G:T	A230E	0.996
X:72208411:A:T	I119K	0.996
X:72207060:T:A	R569S	0.995
X:72207060:T:G	R569S	0.995
X:72207093:C:A	W558C	0.995
X:72207093:C:G	W558C	0.995
X:72207166:A:G	L534P	0.995
X:72207364:A:G	L468P	0.995
X:72207817:A:G	L317S	0.995
X:72207838:C:T	G310E	0.995
X:72207839:C:G	G310R	0.995
X:72207839:C:T	G310R	0.995
X:72207967:A:G	L267P	0.995

dbSNP variants (sampled 300 via entrez): RS1000307391 (X:72231737 A>G), RS1000381258 (X:72222482 C>T), RS1000648071 (X:72215339 A>G), RS1000698302 (X:72238274 C>T), RS1000732667 (X:72226010 T>C), RS1000749566 (X:72212739 G>A,T), RS1000957922 (X:72216201 C>G,T), RS1000976185 (X:72213325 C>G), RS1001198820 (X:72223588 C>T), RS1001208732 (X:72223059 G>A), RS1001584182 (X:72234453 C>T), RS1001688472 (X:72223772 A>G), RS1001725912 (X:72213993 T>C), RS1001915857 (X:72204415 T>A,C), RS1002073411 (X:72214577 G>A)

Disease associations

OMIM: gene MIM:300687 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012466_5	Autism spectrum disorder	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724695 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
bisphenol A	decreases expression, affects cotreatment, increases methylation	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	increases expression	2
Oxygen	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression, affects expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
phenethyl isothiocyanate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	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
CHEMBL5697509	Binding	Inhibition of ERCC6L (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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0CV	Ubigene HeLa ERCC6L KO	Cancer cell line	Female
CVCL_SM36	HAP1 ERCC6L (-) 1	Cancer cell line	Male
CVCL_SM37	HAP1 ERCC6L (-) 2	Cancer cell line	Male
CVCL_SM38	HAP1 ERCC6L (-) 3	Cancer cell line	Male
CVCL_SM39	HAP1 ERCC6L (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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