SKIC8

Summary

SKIC8 (SKI8 subunit of superkiller complex, HGNC:30300) is a protein-coding gene on chromosome 15q25.1, encoding Superkiller complex protein 8 (Q9GZS3). Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. It is a selective cancer dependency (DepMap: 81.0% of cell lines).

WDR61 is a subunit of the human PAF and SKI complexes, which function in transcriptional regulation and are involved in events downstream of RNA synthesis, such as RNA surveillance (Zhu et al., 2005 [PubMed 16024656]).

Source: NCBI Gene 80349 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 81.0% of screened cell lines
• MANE Select transcript: NM_025234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30300
Approved symbol	SKIC8
Name	SKI8 subunit of superkiller complex
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	REC14, SKI8
Ensembl gene	ENSG00000140395
Ensembl biotype	protein_coding
OMIM	609540
Entrez	80349

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000267973, ENST00000558311, ENST00000558412, ENST00000558453, ENST00000558459, ENST00000558840, ENST00000559332, ENST00000559700, ENST00000559848, ENST00000559940, ENST00000560063, ENST00000560569, ENST00000560610, ENST00000560807, ENST00000560946, ENST00000561347, ENST00000910472, ENST00000910473, ENST00000910474, ENST00000925875, ENST00000925876, ENST00000925877, ENST00000925878, ENST00000925879, ENST00000925880, ENST00000959543, ENST00000959544

RefSeq mRNA: 3 — MANE Select: NM_025234 NM_001303247, NM_001303248, NM_025234

CCDS: CCDS10300, CCDS76785

Canonical transcript exons

ENST00000267973 — 11 exons

Exon	Start	End
ENSE00000942861	78292616	78292788
ENSE00000942868	78285261	78285339
ENSE00002551425	78299562	78299609
ENSE00003458241	78288289	78288382
ENSE00003463647	78289619	78289712
ENSE00003497351	78294946	78294973
ENSE00003525553	78286041	78286133
ENSE00003539260	78293167	78293272
ENSE00003613752	78283235	78283521
ENSE00003621615	78289951	78290099
ENSE00003653013	78295675	78295725

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3321 / max 224.4737, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151107	27.4473	1807
151108	4.2479	1617
151109	0.6369	340

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	97.97	gold quality
corpus epididymis	UBERON:0004359	97.50	gold quality
pituitary gland	UBERON:0000007	96.95	gold quality
right uterine tube	UBERON:0001302	96.88	gold quality
adenohypophysis	UBERON:0002196	96.74	gold quality
nephron tubule	UBERON:0001231	96.72	gold quality
esophagus squamous epithelium	UBERON:0006920	96.57	gold quality
adult organism	UBERON:0007023	96.53	gold quality
parotid gland	UBERON:0001831	96.41	gold quality
gingival epithelium	UBERON:0001949	96.38	gold quality
parietal pleura	UBERON:0002400	96.36	gold quality
palpebral conjunctiva	UBERON:0001812	96.34	gold quality
skin of leg	UBERON:0001511	96.30	gold quality
visceral pleura	UBERON:0002401	96.30	gold quality
skin of hip	UBERON:0001554	96.29	gold quality
upper leg skin	UBERON:0004262	96.29	gold quality
skin of abdomen	UBERON:0001416	96.26	gold quality
bronchial epithelial cell	CL:0002328	96.23	gold quality
zone of skin	UBERON:0000014	96.22	gold quality
left lobe of thyroid gland	UBERON:0001120	96.12	gold quality
right adrenal gland	UBERON:0001233	96.12	gold quality
left adrenal gland	UBERON:0001234	96.12	gold quality
right adrenal gland cortex	UBERON:0035827	96.10	gold quality
right lobe of thyroid gland	UBERON:0001119	96.01	gold quality
squamous epithelium	UBERON:0006914	96.01	gold quality
left testis	UBERON:0004533	96.00	gold quality
right testis	UBERON:0004534	96.00	gold quality
epithelium of esophagus	UBERON:0001976	95.99	gold quality
left adrenal gland cortex	UBERON:0035825	95.99	gold quality
thyroid gland	UBERON:0002046	95.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	828.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

18 targeting SKIC8, 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-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-3678-5P	96.64	74.02	93

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 81.0% of screened cell lines.

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	skic8	ENSDARG00000007755
mus_musculus	Skic8	ENSMUSG00000061559
rattus_norvegicus	Skic8	ENSRNOG00000012803
drosophila_melanogaster	CG3909	FBGN0027524
caenorhabditis_elegans	F02E9.10	WBGENE00008533
caenorhabditis_elegans		WBGENE00018213

Paralogs (1): UTP4 (ENSG00000141076)

Protein

Protein identifiers

Superkiller complex protein 8 — Q9GZS3 (reviewed: Q9GZS3)

Alternative names: Meiotic recombination REC14 protein homolog, WD repeat-containing protein 61

All UniProt accessions (7): Q9GZS3, H0YL19, H0YLA1, H0YM76, H0YMF9, H0YN81, H3BQA8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and ‘Ser-2’- and ‘Ser-5’-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 ‘Lys-4’ (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of ‘Lys-120’ of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3’ end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 ‘Lys-4’ (H3K4me3), dimethylation on histone H3 ‘Lys-79’ (H3K4me3). Required for Hox gene transcription. Also acts as a component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways. The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3’-5’ direction and channels mRNA to the cytosolic exosome for degradation. SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling.

Subunit / interactions. Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. The PAF1 complex interacts with PHF5A. Within the PAF1 complex interacts directly with PHF5A. Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the SKI8 family.

RefSeq proteins (3): NP_001290176, NP_001290177, NP_079510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051510	SKI8	Family

Pfam: PF00400

UniProt features (58 total): strand 33, turn 8, repeat 7, sequence conflict 5, chain 2, modified residue 2, initiator methionine 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
9HVQ	ELECTRON MICROSCOPY	2
3OW8	X-RAY DIFFRACTION	2.3
9MLC	ELECTRON MICROSCOPY	2.4
7OOP	ELECTRON MICROSCOPY	2.9
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
7OPC	ELECTRON MICROSCOPY	3
7OPD	ELECTRON MICROSCOPY	3
7UNC	ELECTRON MICROSCOPY	3
7UND	ELECTRON MICROSCOPY	3
6GMH	ELECTRON MICROSCOPY	3.1
6TED	ELECTRON MICROSCOPY	3.1
7QDY	ELECTRON MICROSCOPY	3.1
9EH1	ELECTRON MICROSCOPY	3.1
9EH2	ELECTRON MICROSCOPY	3.1
8A3Y	ELECTRON MICROSCOPY	3.3
9G8O	ELECTRON MICROSCOPY	3.4
9G8R	ELECTRON MICROSCOPY	3.4
7QDZ	ELECTRON MICROSCOPY	3.6
9EH0	ELECTRON MICROSCOPY	3.6
7QDR	ELECTRON MICROSCOPY	3.7
7QDS	ELECTRON MICROSCOPY	3.8
9RTT	ELECTRON MICROSCOPY	4.01
9G8Q	ELECTRON MICROSCOPY	4.1
9S3G	ELECTRON MICROSCOPY	6.4
9S0U	ELECTRON MICROSCOPY	6.72
9RZE	ELECTRON MICROSCOPY	8.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZS3-F1	96.45	0.94

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 (2): 1, 2

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-429958	mRNA decay by 3’ to 5’ exoribonuclease
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-392499	Metabolism of proteins
R-HSA-429914	Deadenylation-dependent mRNA decay
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8852135	Protein ubiquitination
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 176 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, WANG_CLIM2_TARGETS_UP, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GNF2_MCM5, MODULE_308, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_TRANSLATION, GOBP_REGULATION_OF_HEMOPOIESIS, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP

GO Biological Process (5): transcription elongation by RNA polymerase II (GO:0006368), Wnt signaling pathway (GO:0016055), negative regulation of myeloid cell differentiation (GO:0045638), nuclear-transcribed mRNA catabolic process, 3’-5’ exonucleolytic nonsense-mediated decay (GO:0070478), rescue of stalled cytosolic ribosome (GO:0072344)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), Cdc73/Paf1 complex (GO:0016593), Ski complex (GO:0055087), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Deadenylation-dependent mRNA decay	1
Protein ubiquitination	1
Dengue Virus-Host Interactions	1
CHD chromatin remodelers	1
Metabolism of RNA	1
Metabolism of proteins	1
Gene expression (Transcription)	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
DNA-templated transcription elongation	1
transcription by RNA polymerase II	1
cell surface receptor signaling pathway	1
myeloid cell differentiation	1
negative regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
cytoplasmic translational elongation	1
ribosome disassembly	1
binding	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
transcription elongation factor complex	1
RNA polymerase II, holoenzyme	1
protein-containing complex	1
cellular_component	1

Protein interactions and networks

STRING

2356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SKIC8	SKIC2	Q15477	998
SKIC8	SKIC3	Q6PGP7	998
SKIC8	LEO1	Q8WVC0	997
SKIC8	CTR9	Q6PD62	997
SKIC8	RTF1	Q92541	997
SKIC8	CDC73	Q6P1J9	996
SKIC8	SPO11	Q9Y5K1	868
SKIC8	MTREX	P42285	734
SKIC8	EXOSC1	Q9Y3B2	727
SKIC8	HBS1L	Q9Y450	709
SKIC8	REC114	Q7Z4M0	690
SKIC8	EXOSC10	Q01780	679
SKIC8	XRN1	Q8IZH2	663
SKIC8	EXOSC4	Q9NPD3	663
SKIC8	CD151	P48509	631

IntAct

299 interactions, top by confidence:

A	B	Type	Score
PAF1	CDC73	psi-mi:“MI:0914”(association)	0.960
CDC73	CTR9	psi-mi:“MI:0914”(association)	0.940
CTR9	CDC73	psi-mi:“MI:0914”(association)	0.940
CDC73	CTR9	psi-mi:“MI:0915”(physical association)	0.940
PAF1	CTR9	psi-mi:“MI:0914”(association)	0.910
CTR9	PAF1	psi-mi:“MI:0914”(association)	0.910
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CTR9	SKIC8	psi-mi:“MI:0915”(physical association)	0.850
RTF1	CDC73	psi-mi:“MI:0914”(association)	0.750
CUL4B	CUL4A	psi-mi:“MI:0914”(association)	0.730
POLR2D	POLR2K	psi-mi:“MI:0915”(physical association)	0.730
PHF5A	SF3B1	psi-mi:“MI:0914”(association)	0.730
HTT	SKIC8	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (537): WDR61 (Affinity Capture-MS), WDR61 (Affinity Capture-MS), WDR61 (Affinity Capture-MS), CDC73 (Co-fractionation), CTR9 (Co-fractionation), DDX3X (Co-fractionation), DNAJC2 (Co-fractionation), ERCC2 (Co-fractionation), RNF40 (Co-fractionation), WDR61 (Co-fractionation), WDR61 (Co-fractionation), WDR61 (Co-fractionation), WDR61 (Affinity Capture-MS), WDR61 (Affinity Capture-MS), WDR61 (Affinity Capture-MS)

ESM2 similar proteins: A4QNE6, B0BNA7, B3MEY6, B3S4I5, B5FZ19, C4Q0P6, D3TLL6, D3Z7A5, O43172, O74184, P41318, Q13347, Q17N69, Q29RH4, Q2HJH6, Q2TBP4, Q32LN7, Q38884, Q3KQ62, Q3MHE2, Q4V7A0, Q54D08, Q5BK30, Q5BLX8, Q5E966, Q5EBE8, Q5IH81, Q5NVD0, Q5R7R2, Q5RF51, Q5XGI5, Q5ZJH5, Q66J51, Q6DH44, Q6GMD2, Q6PBD6, Q6PE01, Q8JZX3, Q8NBT0, Q8VE80

Diamond homologs: A0A223GEB2, A0CH87, A0DB19, A1CF18, A1D3F5, A2QPZ4, A2RRU4, A5D7H2, A6QM06, A6RRD4, A6ZQL5, A8Q2R5, A8XYW9, B2AEZ5, B8N9H4, C0NRC6, C5PFX0, C6HTE8, D1ZEB4, D4AZ50, D4DG66, E7FAG6, G0S8H7, G1SJB4, G4MQX3, O14170, O14727, O18640, O24076, O24456, O42248, O42249, O48716, O94527, P0DL28, P25382, P25387, P38011, P46800, P47025

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDR61	“form complex”	PAF1C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Formation of RNA Pol II elongation complex	10	28.9×	2e-10
RNA Polymerase II Transcription Elongation	10	28.9×	2e-10
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	7	27.8×	3e-07
Pausing and recovery of Tat-mediated HIV elongation	5	27.5×	3e-05
Tat-mediated HIV elongation arrest and recovery	5	27.5×	3e-05
HIV elongation arrest and recovery	5	25.8×	3e-05
Pausing and recovery of HIV elongation	5	25.8×	3e-05
Formation of TC-NER Pre-Incision Complex	8	25.2×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
transcription elongation by RNA polymerase II	7	37.9×	3e-07
amyloid fibril formation	5	36.7×	7e-05
stem cell population maintenance	5	25.7×	2e-04
adult locomotory behavior	6	22.0×	7e-05
learning	5	17.1×	9e-04
memory	5	11.2×	4e-03
locomotory behavior	5	10.9×	5e-03
response to oxidative stress	6	9.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2284 predictions. Top by Δscore:

Variant	Effect	Δscore
15:78280044:GGT:G	acceptor_gain	1.0000
15:78280141:TTTTA:T	donor_gain	1.0000
15:78280142:TTTA:T	donor_gain	1.0000
15:78280146:G:GG	donor_gain	1.0000
15:78280235:C:G	acceptor_gain	1.0000
15:78280243:A:AC	acceptor_loss	1.0000
15:78280244:G:GC	acceptor_loss	1.0000
15:78285336:CGAA:C	acceptor_gain	1.0000
15:78285340:C:CC	acceptor_gain	1.0000
15:78286036:AGTAC:A	donor_loss	1.0000
15:78286037:GTAC:G	donor_loss	1.0000
15:78286038:TA:T	donor_loss	1.0000
15:78286039:A:AT	donor_loss	1.0000
15:78286040:CCTG:C	donor_loss	1.0000
15:78288287:A:AC	donor_gain	1.0000
15:78288288:C:CC	donor_gain	1.0000
15:78288288:CA:C	donor_gain	1.0000
15:78288288:CACA:C	donor_gain	1.0000
15:78288288:CACAT:C	donor_gain	1.0000
15:78288379:TGGC:T	acceptor_gain	1.0000
15:78288383:C:CC	acceptor_gain	1.0000
15:78288841:ACC:A	donor_gain	1.0000
15:78288842:CCC:C	donor_gain	1.0000
15:78288962:C:CT	acceptor_gain	1.0000
15:78288969:C:CT	acceptor_gain	1.0000
15:78288969:C:T	acceptor_gain	1.0000
15:78289614:TATA:T	donor_loss	1.0000
15:78289616:TACC:T	donor_loss	1.0000
15:78289617:A:AT	donor_loss	1.0000
15:78289618:C:CG	donor_loss	1.0000

AlphaMissense

2016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:78285314:A:G	W259R	1.000
15:78285314:A:T	W259R	1.000
15:78286047:A:T	V248D	1.000
15:78288313:T:A	D211V	1.000
15:78288314:C:G	D211H	1.000
15:78288325:G:A	T207I	1.000
15:78288351:A:C	F198L	1.000
15:78288351:A:T	F198L	1.000
15:78288353:A:G	F198L	1.000
15:78289672:C:T	G170E	1.000
15:78289684:C:T	G166E	1.000
15:78289690:G:T	A164D	1.000
15:78292664:A:G	W91R	1.000
15:78292664:A:T	W91R	1.000
15:78283478:G:A	S291F	0.999
15:78283479:A:G	S291P	0.999
15:78283506:A:C	Y282D	0.999
15:78285312:C:A	W259C	0.999
15:78285312:C:G	W259C	0.999
15:78285331:T:A	D253V	0.999
15:78285332:C:G	D253H	0.999
15:78285337:G:C	S251W	0.999
15:78285338:A:G	S251P	0.999
15:78285339:A:C	S250R	0.999
15:78285339:A:T	S250R	0.999
15:78286042:T:G	S250R	0.999
15:78286044:G:A	S249F	0.999
15:78286044:G:T	S249Y	0.999
15:78286045:A:G	S249P	0.999
15:78286090:A:G	W234R	0.999

dbSNP variants (sampled 300 via entrez): RS1000105138 (15:78291310 A>G), RS1000181659 (15:78298357 A>G), RS1000304198 (15:78297585 T>C), RS1000362330 (15:78291884 T>C), RS1000688443 (15:78284382 C>A), RS1000749219 (15:78293193 T>C), RS1000816552 (15:78291611 T>C), RS1000831961 (15:78286794 G>T), RS1000968363 (15:78296726 C>G,T), RS1001567475 (15:78291015 T>C), RS1002191709 (15:78301069 CTT>C), RS1002214295 (15:78301577 T>C), RS1002375302 (15:78295220 C>A), RS1002422370 (15:78296169 G>A), RS1002476092 (15:78301322 T>C)

Disease associations

OMIM: gene MIM:609540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003476_6	Eyebrow thickness	1.000000e-06
GCST010083_49	Hemoglobin levels	1.000000e-14
GCST90002405_344	Reticulocyte count	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725101 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	Kd	60	nM	MOLIBRESIB
7.16	Kd	69	nM	MOLIBRESIB
7.05	IC50	90	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2174627: Binding affinity to WDR61 (unknown origin) assessed as apparent dissociation constant	kd	0.0600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Rotenone	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
deguelin	decreases expression	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
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Vorinostat	decreases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects response to substance	1
Fluorouracil	decreases expression, affects reaction	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Ozone	increases expression, increases abundance, affects cotreatment	1
Quercetin	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5696857	Binding	Binding affinity to WDR61 (unknown origin) assessed as apparent dissociation constant	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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