QKI

Summary

QKI (QKI, KH domain containing RNA binding, HGNC:21100) is a protein-coding gene on chromosome 6q26, encoding KH domain-containing RNA-binding protein QKI (Q96PU8). RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and/or translation.

The protein encoded by this gene is an RNA-binding protein that regulates pre-mRNA splicing, export of mRNAs from the nucleus, protein translation, and mRNA stability. The encoded protein is involved in myelinization and oligodendrocyte differentiation and may play a role in schizophrenia. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9444 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 49 total
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_006775

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21100
Approved symbol	QKI
Name	QKI, KH domain containing RNA binding
Location	6q26
Locus type	gene with protein product
Status	Approved
Aliases	QK3
Ensembl gene	ENSG00000112531
Ensembl biotype	protein_coding
OMIM	609590
Entrez	9444

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 25 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000275262, ENST00000361195, ENST00000361752, ENST00000361758, ENST00000392127, ENST00000424802, ENST00000453779, ENST00000537041, ENST00000537124, ENST00000537883, ENST00000540719, ENST00000541696, ENST00000544361, ENST00000544436, ENST00000544823, ENST00000545346, ENST00000545607, ENST00000873379, ENST00000873380, ENST00000873381, ENST00000930427, ENST00000930428, ENST00000930429, ENST00000946869, ENST00000946870, ENST00000946871, ENST00000946872, ENST00000946873, ENST00000946874, ENST00000946875

RefSeq mRNA: 5 — MANE Select: NM_006775 NM_001301085, NM_006775, NM_206853, NM_206854, NM_206855

CCDS: CCDS43525, CCDS5285, CCDS5286, CCDS5287, CCDS75546

Canonical transcript exons

ENST00000361752 — 8 exons

Exon	Start	End
ENSE00002220775	163570694	163578592
ENSE00003537009	163561982	163562069
ENSE00003541484	163478780	163478896
ENSE00003543768	163563420	163563719
ENSE00003550421	163534982	163535125
ENSE00003577192	163566721	163566795
ENSE00003658138	163455279	163455421
ENSE00003841802	163414718	163415335

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 107.2696 / max 3636.3683, expressed in 1820 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71106	33.0716	1810
71108	25.2204	1768
71105	12.0573	1667
71107	11.1591	1726
71109	10.7987	1638
71104	6.2244	1600
71101	2.4941	597
71102	2.2332	889
71100	0.8992	390
71132	0.7241	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.94	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.93	gold quality
corpus callosum	UBERON:0002336	99.88	gold quality
inferior olivary complex	UBERON:0002127	99.86	gold quality
inferior vagus X ganglion	UBERON:0005363	99.86	gold quality
lateral globus pallidus	UBERON:0002476	99.85	gold quality
medulla oblongata	UBERON:0001896	99.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.82	gold quality
subthalamic nucleus	UBERON:0001906	99.81	gold quality
globus pallidus	UBERON:0001875	99.79	gold quality
superior vestibular nucleus	UBERON:0007227	99.78	gold quality
medial globus pallidus	UBERON:0002477	99.76	gold quality
CA1 field of hippocampus	UBERON:0003881	99.76	gold quality
ventral tegmental area	UBERON:0002691	99.74	gold quality
cranial nerve II	UBERON:0000941	99.70	gold quality
substantia nigra pars compacta	UBERON:0001965	99.70	gold quality
trigeminal ganglion	UBERON:0001675	99.61	gold quality
pons	UBERON:0000988	99.59	gold quality
ventricular zone	UBERON:0003053	99.59	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.42	gold quality
middle frontal gyrus	UBERON:0002702	99.37	gold quality
secondary oocyte	CL:0000655	99.36	gold quality
tibia	UBERON:0000979	99.35	gold quality
parietal lobe	UBERON:0001872	99.30	gold quality
postcentral gyrus	UBERON:0002581	99.30	gold quality
olfactory bulb	UBERON:0002264	99.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.22	gold quality
spinal cord	UBERON:0002240	99.20	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	6002.86
E-HCAD-25	yes	5552.60
E-HCAD-35	yes	5148.62
E-MTAB-9221	yes	25.95
E-ANND-3	yes	17.83
E-GEOD-180759	no	8020.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

267 targeting QKI, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
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

Literature-anchored findings (GeneRIF, showing 40)

• There are many isoforms of this RNA binding protein. QKI-6 has been shown to be a translational repressor. (PMID:10535969)
• QKI as a possible target for functional studies related to the role of myelination in schizophrenia. (PMID:16342280)
• QKI levels may regulate oligodendrocyte differentiation and maturation in human brain (PMID:16641098)
• Since QKI plays a fundamental role in oligodendrocyte differentiation and in myelination, its underexpression may be pivotal to, and upstream of, other myelin-associated gene expression abnormalities in schizophrenia. (PMID:17012699)
• QKI-6 is the major protein isoform responsible for central nervous system (CNS) myelination, which promotes myelin basic protein expression in oligodendrocytes. (PMID:17079655)
• biological functions attributed to this KH-type RNA binding protein and the recent achievements linking it to human disorders (PMID:17787018)
• we examined expression of QKI and several putative mRNA targets of QKI in human PFC and hippocampus at different ages (PMID:17918747)
• variants within the promoter region of QKI gene are unlikely to play a major role in susceptibility to schizophrenia in the Chinese population (PMID:18938205)
• The observation of consistent reductions in multiple isoforms of QKI mRNA in depressed suicide victims supports the growing body of evidence for a role of myelination-related deficits in the etiology of psychiatric disorders (PMID:19545858)
• QKI functions as a principal regulator in the differentiation of colon epithelium and a suppressor of carcinogenesis through coordinately targeting multiple genes associated with cell growth and differentiation (PMID:19686745)
• The QKI RNA-binding proteins regulate oligodendrocyte differentiation by modulating the expression of AIP-1. (PMID:20631256)
• QKI-7 regulates expression of interferon-related genes in human astrocyte glioma cells. (PMID:20927331)
• HSV-1 infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells (PMID:21467216)
• E2F1 directly transcribes QKI, which, in turn, negatively regulates the cell cycle by targeting multiple cell cycle regulators, forming an E2F1-QKI-pRb/E2F1 negative feedback loop. (PMID:21768773)
• QKI, regulates the alternative splicing of macroH2A1 pre-mRNA, resulting in increased levels of macroH2A1.1. (PMID:21844227)
• The RNA-binding protein QKI5 is a direct target of C/EBPalpha and delays macrophage differentiation. (PMID:22398723)
• Findings suggest that miR-574-5p is a potent ribo-regulator for Qkis and that aberrant miR-574-5p upregulation can be oncogenic. (PMID:22490519)
• Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival. (PMID:22569043)
• establish that p53 directly regulates Quaking (QKI) gene expression, and QKI protein associates with and leads to the stabilization of miR-20a (PMID:22751500)
• QKI is a hub regulator of glia function in humans. (PMID:23321059)
• Data showed that like QKI5/6/7 proteins, QKI7b protein was also significantly downregulated in most human colorectal cancer tissues. (PMID:23440637)
• This work provides the first evidence that QK is a global regulator of splicing during muscle development in vertebrates and shows how overlapping splicing regulatory networks contribute to gene expression programs during differentiation. (PMID:23525800)
• Propose that QKI is a central regulator of VSMC phenotypic plasticity and that intervention in QKI activity can ameliorate pathogenic, fibroproliferative responses to vascular injury. (PMID:23963726)
• the QKI-5 expression may be a novel, independent factor in the prognosis of prostate cancer patients. (PMID:24153116)
• QKI-mediated repression of FOXO1 may be one of the factors contributing to the oncogenesis and progression of breast carcinoma. (PMID:24398626)
• QKI as a key regulator of alternative splicing in lung cancer. (PMID:24722255)
• QKI is a novel Cancer stem cells (CSC) inhibitor and impaired multiple oral CSC properties via partial repression of SOX2. (PMID:24918581)
• miR-155 regulates the cell cycle and invasion ability of colon cancer cells via the modulation of QKI expression (PMID:25420938)
• Using circScreen, study identified the RNA binding protein Quaking (QKI) as a major regulator of circRNA biogenesis in epithelial-mesenchymal transition (EMT) and show that introduction of consensus binding sequences for QKI into the flanking introns is sufficient to cause circRNAs to be produced from exons that normally only undergo canonical linear splicing. (PMID:25768908)
• miR-29a promotes scavenger receptor A expression by targeting QKI during monocyte-macrophage differentiation. (PMID:26056009)
• Data implicate QKI in the pathophysiology of inflammation and leukemoogenesis where miR-155 is involved. (PMID:26337206)
• MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of the tumor suppressor QKI (PMID:26829751)
• quaking is essential in maintaining endothelial barrier function. (PMID:26905650)
• QKI-7 recruits PAPD4 to regulate post-transcriptional polyadenylation of target mRNAs. (PMID:26926106)
• QKI has a role in posttranscriptionally guiding macrophage identity and function. (PMID:27029405)
• The results of this study have found an upregulation of QKI and its isoforms (QKI5, QKI6 and QKI7) in Sporadic Alzheimer’s Disease patients compared to controls (PMID:27163826)
• several splicing variants with functional relevance in lung cancer largely regulated by the splicing factor QKI, were identified. (PMID:27555542)
• QKI underexpression is associated with glioma. (PMID:27841882)
• Methylation of the QKI promoter and concomitant reduced expression of QKI mRNA may be important for CRC initiation and progression. (PMID:28179294)
• Study examined if QKI6B expression can predict the outcome of GFAP, and several oligodendrocyte-related genes, in the prefrontal cortex of brain samples of schizophrenic individuals. QKI6B significantly predicts the expression of GFAP, but does not predict oligodendrocyte-related gene outcome, as previously seen with other QKI isoforms. (PMID:28552414)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	qkib	ENSDARG00000002026
mus_musculus	Qki	ENSMUSG00000062078
rattus_norvegicus	Qki	ENSRNOG00000048297
drosophila_melanogaster	qkr58E-3	FBGN0022984
drosophila_melanogaster	qkr58E-2	FBGN0022985
drosophila_melanogaster	qkr58E-1	FBGN0022986
drosophila_melanogaster	qkr54B	FBGN0022987
drosophila_melanogaster	CG4021	FBGN0034659
drosophila_melanogaster	CG10384	FBGN0034731
drosophila_melanogaster	CG3927	FBGN0034739
drosophila_melanogaster	nsr	FBGN0034740

Paralogs (4): KHDRBS2 (ENSG00000112232), KHDRBS1 (ENSG00000121774), KHDRBS3 (ENSG00000131773), SF1 (ENSG00000168066)

Protein

Protein identifiers

KH domain-containing RNA-binding protein QKI — Q96PU8 (reviewed: Q96PU8)

Alternative names: Protein quaking

All UniProt accessions (9): Q96PU8, F5GXS8, F5GYM3, F5GYT7, F5H5U6, F5H8C8, H0YFB7, H0YG47, H0YGD6

UniProt curated annotations — full annotation on UniProt →

Function. RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and/or translation. Involved in various cellular processes, such as mRNA storage into stress granules, apoptosis, lipid deposition, interferon response, glial cell fate and development. Binds to the 5’-NACUAAY-N(1,20)-UAAY-3’ RNA core sequence. Acts as a mRNA modification reader that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G). Promotes the formation of circular RNAs (circRNAs) during the epithelial to mesenchymal transition and in cardiomyocytes: acts by binding to sites flanking circRNA-forming exons. CircRNAs are produced by back-splicing circularization of pre-mRNAs. Plays a central role in myelinization via 3 distinct mechanisms. First, acts by protecting and promoting stability of target mRNAs such as MBP, SIRT2 and CDKN1B, which promotes oligodendrocyte differentiation. Second, participates in mRNA transport by regulating the nuclear export of MBP mRNA. Finally, indirectly regulates mRNA splicing of MAG pre-mRNA during oligodendrocyte differentiation by acting as a negative regulator of MAG exon 12 alternative splicing: acts by binding to HNRNPA1 mRNA splicing factor, preventing its translation. Involved in microglia differentiation and remyelination by regulating microexon alternative splicing of the Rho GTPase pathway. Involved in macrophage differentiation: promotes monocyte differentiation by regulating pre-mRNA splicing in naive peripheral blood monocytes. Acts as an important regulator of muscle development: required for the contractile function of cardiomyocytes by regulating alternative splicing of cardiomyocyte transcripts. Acts as a negative regulator of thermogenesis by decreasing stability, nuclear export and translation of mRNAs encoding PPARGC1A and UCP1. Also required for visceral endoderm function and blood vessel development. May also play a role in smooth muscle development. In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2. Nuclear isoform that acts as an indirect regulator of mRNA splicing. Regulates mRNA splicing of MAG pre-mRNA by inhibiting translation of HNRNPA1 mRNA, thereby preventing MAG exon 12 alternative splicing. Involved in oligodendrocyte differentiation by promoting stabilization of SIRT2 mRNA. Acts as a negative regulator of the interferon response by binding to MAVS mRNA, downregulating its expression. Also inhibits the interferon response by binding to fibrinectin FN1 pre-mRNA, repressing EDA exon inclusion in FN1. Delays macrophage differentiation by binding to CSF1R mRNA, promoting its degradation. In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2, promoting SREBF2/SREBP2-dependent cholesterol biosynthesis. SREBF2/SREBP2-dependent cholesterol biosynthesis participates to myelinization and is required for eye lens transparency. Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation. Acts as a translational repressor for HNRNPA1 and GLI1. Translation inhibition of HNRNPA1 during oligodendrocyte differentiation prevents inclusion of exon 12 in MAG pre-mRNA splicing. Involved in astrocyte differentiation by regulating translation of target mRNAs. Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation. Acts as a negative regulator of angiogenesis by binding to mRNAs encoding CDH5, NLGN1 and TNFAIP6, promoting their degradation. Can also induce apoptosis in the cytoplasm. Heterodimerization with other isoforms results in nuclear translocation of isoform QKI7 and suppression of apoptosis. Also binds some microRNAs: promotes stabilitation of miR-122 by mediating recruitment of poly(A) RNA polymerase TENT2, leading to 3’ adenylation and stabilization of miR-122.

Subunit / interactions. Homodimer; does not require RNA to homodimerize. Able to heterodimerize with BICC1. Interacts with G3BP1; directing N(7)-methylguanine (m7G)-containing mRNAs to stress granules to suppress mRNA translation. Interacts with G3BP1; directing N(7)-methylguanine (m7G)-containing mRNAs to stress granules to suppress mRNA translation. Interacts with TENT2; promoting stabilization of miR-122.

Subcellular location. Nucleus. Cytoplasm Nucleus. Cytoplasm Cytoplasm. Cytosol. Nucleus Cytoplasm. Cytoplasm. Stress granule.

Tissue specificity. Expressed in the frontal cortex of brain. Down-regulated in the brain of schizophrenic patients.

Post-translational modifications. Methylated by PRMT1. Tyrosine phosphorylated at its C-terminus, probably by FYN. Phosphorylation leads to decreased mRNA-binding affinity, affecting transport and/or stabilization of MBP mRNA. Ubiquitinated by RNF6 in macrophages, leading to its degradation.

Domain organisation. The KH domain and the Qua2 region are involved in RNA binding.

Induction. Expression is activated by CEBPA furing macrophage differentiation.

Similarity. Belongs to the quaking family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96PU8-1	QKI5, HQK-5, QKI-5	yes
Q96PU8-3	2
Q96PU8-5	3
Q96PU8-6	QKI7, HQK-7, QKI-7
Q96PU8-8	QKI7B, HQK-7B
Q96PU8-9	QKI6, QKI-6

RefSeq proteins (5): NP_001288014, NP_006766, NP_996735, NP_996736, NP_996737 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR032367	Quaking_NLS	Domain
IPR032377	STAR_dimer	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR045071	BBP-like	Family
IPR055256	KH_1_KHDC4/BBP-like	Domain

Pfam: PF16544, PF16551, PF22675

UniProt features (30 total): site 6, mutagenesis site 6, modified residue 5, splice variant 4, region of interest 2, sequence conflict 2, short sequence motif 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4JVH	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PU8-F1	69.68	0.31

Functional residue map

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

Catalytic / active sites (6): 190 (involved in rna binding); 193 (involved in rna binding); 97 (involved in rna binding); 120 (involved in rna binding); 124 (involved in rna binding); 130 (involved in rna binding)

Post-translational modifications (5): 188, 227, 242, 242, 256

Mutagenesis-validated functional residues (6):

Position	Phenotype
97	decrease in target mrna abundance and 10-fold decrease in rna binding affinity; when associated with a-130.
120	decrease in target mrna abundance and 20-fold decrease in rna binding affinity; when associated with a-124.
124	decrease in target mrna abundance and 20-fold decrease in rna binding affinity; when associated with a-120.
130	decrease in target mrna abundance and 10-fold decrease in rna binding affinity; when associated with a-97.
190	decrease in target mrna abundance and 124-fold decrease in rna binding affinity; when associated with a-193.
193	decrease in target mrna abundance and 124-fold decrease in rna binding affinity; when associated with a-190.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6802952	Signaling by BRAF and RAF1 fusions

MSigDB gene sets: 684 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, TGGTGCT_MIR29A_MIR29B_MIR29C, SHEPARD_BMYB_MORPHOLINO_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, AAGCAAT_MIR137, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, TTTGTAG_MIR520D, AAGCCAT_MIR135A_MIR135B

GO Biological Process (35): vasculogenesis (GO:0001570), spermatid development (GO:0007286), intracellular mRNA localization (GO:0008298), regulation of epithelial to mesenchymal transition (GO:0010717), microglia differentiation (GO:0014004), negative regulation of angiogenesis (GO:0016525), negative regulation of translation (GO:0017148), positive regulation of myelination (GO:0031643), negative regulation of type I interferon production (GO:0032480), vascular associated smooth muscle cell differentiation (GO:0035886), myelination (GO:0042552), long-chain fatty acid biosynthetic process (GO:0042759), positive regulation of cholesterol biosynthetic process (GO:0045542), regulation of macrophage differentiation (GO:0045649), negative regulation of macrophage differentiation (GO:0045650), regulation of mRNA splicing, via spliceosome (GO:0048024), mRNA stabilization (GO:0048255), regulation of astrocyte differentiation (GO:0048710), positive regulation of oligodendrocyte differentiation (GO:0048714), mRNA transport (GO:0051028), negative regulation of cold-induced thermogenesis (GO:0120163), spliceosome-depend formation of circular RNA (GO:0160091), negative regulation of 3’-UTR-mediated mRNA stabilization (GO:1905869), myofibroblast contraction (GO:1990764), negative regulation of miRNA catabolic process (GO:2000626), mRNA processing (GO:0006397), regulation of translation (GO:0006417), axon ensheathment (GO:0008366), RNA splicing (GO:0008380), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), stress granule assembly (GO:0034063), positive regulation of DNA-templated transcription (GO:0045893), regulation of cell development (GO:0060284), regulation of multicellular organismal development (GO:2000026)

GO Molecular Function (10): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), SH3 domain binding (GO:0017124), miRNA binding (GO:0035198), internal N(7)-methylguanine-containing RNA reader activity (GO:0160089), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), synapse (GO:0045202), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Oncogenic MAPK signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macrophage differentiation	3
nucleic acid binding	2
RNA binding	2
binding	2
cellular anatomical structure	2
cell differentiation	1
blood vessel morphogenesis	1
germ cell development	1
spermatid differentiation	1
RNA localization	1
epithelial to mesenchymal transition	1
regulation of cell differentiation	1
central nervous system development	1
glial cell differentiation	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
regulation of myelination	1
positive regulation of nervous system process	1
myelination	1
positive regulation of cellular process	1
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
vasculature development	1
smooth muscle cell differentiation	1
axon ensheathment	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
cholesterol biosynthetic process	1
regulation of cholesterol biosynthetic process	1
positive regulation of cholesterol metabolic process	1
positive regulation of sterol biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
regulation of myeloid leukocyte differentiation	1
negative regulation of myeloid leukocyte differentiation	1

Protein interactions and networks

STRING

2008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
QKI	MBNL1	Q9NR56	896
QKI	MBNL2	Q5VZF2	890
QKI	MBNL3	Q9NUK0	890
QKI	BCAS1	O75363	868
QKI	RBPMS	Q93062	850
QKI	UBR5	O95071	847
QKI	RBFOX2	O43251	837
QKI	FUS	P35637	740
QKI	HNRNPK	P61978	724
QKI	ESRP1	Q6NXG1	719
QKI	ATN1	P54259	718
QKI	EIF4A3	P38919	702
QKI	PLP1	P04400	688
QKI	ESRP2	Q9H6T0	678
QKI	PACRG	Q96M98	663

IntAct

164 interactions, top by confidence:

A	B	Type	Score
HNRNPK	QKI	psi-mi:“MI:0915”(physical association)	0.820
QKI	HNRNPK	psi-mi:“MI:0915”(physical association)	0.820
FUBP3	QKI	psi-mi:“MI:0915”(physical association)	0.740
QKI	FUBP3	psi-mi:“MI:0915”(physical association)	0.740
QKI	RBFOX2	psi-mi:“MI:0914”(association)	0.720
QKI	RBFOX2	psi-mi:“MI:0915”(physical association)	0.720
RBPMS	QKI	psi-mi:“MI:0915”(physical association)	0.700
QKI	RBPMS	psi-mi:“MI:0915”(physical association)	0.700
QKI	HNRNPLL	psi-mi:“MI:0915”(physical association)	0.670
HNRNPLL	QKI	psi-mi:“MI:0915”(physical association)	0.670
SNRPA	QKI	psi-mi:“MI:0915”(physical association)	0.660
QKI	SNRPA	psi-mi:“MI:0915”(physical association)	0.660
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
QKI	PTBP1	psi-mi:“MI:0915”(physical association)	0.630
PCBP1	QKI	psi-mi:“MI:0915”(physical association)	0.620
QKI	RBM11	psi-mi:“MI:0915”(physical association)	0.560
NABP1	QKI	psi-mi:“MI:0915”(physical association)	0.560
RBM11	QKI	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (271): QKI (Two-hybrid), QKI (Two-hybrid), QKI (Two-hybrid), RBPMS (Two-hybrid), RBM11 (Two-hybrid), NABP1 (Two-hybrid), HNRNPLL (Two-hybrid), QKI (Affinity Capture-MS), QKI (Affinity Capture-MS), QKI (Affinity Capture-MS), QKI (Affinity Capture-MS), QKI (Affinity Capture-MS), QKI (Two-hybrid), QKI (Affinity Capture-MS), QKI (Proximity Label-MS)

ESM2 similar proteins: A0A8I6B1J2, A0AV96, A8XND8, B3M3R5, B3NGA1, B4HUE4, B4IX08, B4KX02, B4LFQ9, B4MM23, B4PIS2, B4QRJ0, F2Z3T4, G5EFF1, O01367, P16914, P31367, Q0V9L3, Q24312, Q32NN2, Q56V19, Q5R4F5, Q5R5P4, Q5VZF2, Q5W9D5, Q5W9D6, Q5W9D7, Q5ZKW9, Q66H68, Q6IRN2, Q6P0D0, Q6P104, Q6Q2B2, Q7JJZ8, Q7TSY6, Q8C181, Q8MSV2, Q8R003, Q8R205, Q91WT8

Diamond homologs: G5EFF1, O01367, O74555, O75525, P0CO44, P0CO45, P13230, Q07666, Q08BJ2, Q0VFL3, Q0WLR1, Q12186, Q15637, Q17339, Q32NN2, Q4P0H7, Q4WXV6, Q54BM5, Q5AED9, Q5VWX1, Q5W9D5, Q5W9D6, Q5W9D7, Q60749, Q64213, Q6BSP4, Q6C187, Q6FW77, Q6IRN2, Q6P0D0, Q6P104, Q750X2, Q75GR5, Q7JJZ8, Q8GWR3, Q8GYR4, Q8NIW7, Q8UUW7, Q91V33, Q91XU1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 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
Processing of Capped Intron-Containing Pre-mRNA	11	10.2×	3e-06
mRNA Polyadenylation	10	9.9×	1e-05
Interleukin-4 and Interleukin-13 signaling	7	8.1×	3e-03
mRNA Splicing - Major Pathway	13	8.0×	3e-06
Dengue Virus-Host Interactions	11	5.7×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	9	19.3×	9e-07
RNA processing	6	11.5×	2e-03
regulation of RNA splicing	6	11.5×	2e-03
mRNA splicing, via spliceosome	10	8.0×	3e-04
mRNA processing	9	6.2×	2e-03
nervous system development	11	4.4×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — GBM, MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2314 predictions. Top by Δscore:

Variant	Effect	Δscore
6:163415334:AGGTG:A	donor_loss	1.0000
6:163415336:G:GG	donor_gain	1.0000
6:163415336:GT:G	donor_loss	1.0000
6:163455274:A:AG	acceptor_gain	1.0000
6:163455275:ACAGA:A	acceptor_loss	1.0000
6:163455276:CAGAA:C	acceptor_loss	1.0000
6:163455277:A:AG	acceptor_gain	1.0000
6:163455278:G:GG	acceptor_gain	1.0000
6:163455278:GA:G	acceptor_gain	1.0000
6:163455278:GAA:G	acceptor_gain	1.0000
6:163455417:CAGAT:C	donor_gain	1.0000
6:163455418:AGAT:A	donor_gain	1.0000
6:163455419:GAT:G	donor_gain	1.0000
6:163455419:GATG:G	donor_gain	1.0000
6:163455420:AT:A	donor_gain	1.0000
6:163455421:TGTA:T	donor_loss	1.0000
6:163455422:G:GG	donor_gain	1.0000
6:163455423:T:A	donor_loss	1.0000
6:163455424:AA:A	donor_loss	1.0000
6:163478775:CTCA:C	acceptor_loss	1.0000
6:163478778:A:AG	acceptor_gain	1.0000
6:163478779:G:GT	acceptor_gain	1.0000
6:163478779:GT:G	acceptor_gain	1.0000
6:163478779:GTT:G	acceptor_gain	1.0000
6:163478779:GTTT:G	acceptor_gain	1.0000
6:163478779:GTTTA:G	acceptor_gain	1.0000
6:163478893:AAAG:A	donor_gain	1.0000
6:163478894:AAG:A	donor_gain	1.0000
6:163478894:AAGG:A	donor_loss	1.0000
6:163478894:AAGGT:A	donor_gain	1.0000

AlphaMissense

2220 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:163415246:T:C	L18P	1.000
6:163415255:T:A	L21Q	1.000
6:163415255:T:C	L21P	1.000
6:163415324:T:C	L44P	1.000
6:163415327:T:C	L45P	1.000
6:163455399:T:A	V88E	1.000
6:163478780:T:C	F96L	1.000
6:163478782:T:A	F96L	1.000
6:163478782:T:G	F96L	1.000
6:163478783:A:G	N97D	1.000
6:163478785:T:A	N97K	1.000
6:163478785:T:G	N97K	1.000
6:163478786:T:C	F98L	1.000
6:163478787:T:C	F98S	1.000
6:163478787:T:G	F98C	1.000
6:163478788:T:A	F98L	1.000
6:163478788:T:G	F98L	1.000
6:163478789:G:C	V99L	1.000
6:163478790:T:A	V99D	1.000
6:163478792:G:A	G100R	1.000
6:163478792:G:C	G100R	1.000
6:163478792:G:T	G100W	1.000
6:163478793:G:A	G100E	1.000
6:163478793:G:C	G100A	1.000
6:163478793:G:T	G100V	1.000
6:163478795:A:G	R101G	1.000
6:163478796:G:C	R101T	1.000
6:163478796:G:T	R101I	1.000
6:163478797:A:C	R101S	1.000
6:163478797:A:T	R101S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001396 (6:163493159 T>A), RS1000007257 (6:163424664 G>C,T), RS1000018046 (6:163471832 C>T), RS1000018788 (6:163511334 C>T), RS1000054511 (6:163469043 T>C), RS1000080980 (6:163431162 T>A), RS1000111539 (6:163446975 C>T), RS1000115721 (6:163480480 T>C), RS1000149940 (6:163550925 C>T), RS1000151194 (6:163471565 G>A), RS1000154195 (6:163510982 T>C), RS1000174147 (6:163528653 T>C), RS1000182938 (6:163526208 T>G), RS1000185030 (6:163449656 T>C), RS1000185810 (6:163576017 A>C,G)

Disease associations

OMIM: gene MIM:609590 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000211_7	Response to TNF antagonist treatment	3.000000e-07
GCST002875_138	Diisocyanate-induced asthma	7.000000e-06
GCST003430_1	Incident myocardial infarction	6.000000e-09
GCST005993_36	Mean corpuscular hemoglobin	2.000000e-19
GCST005996_25	Red blood cell count	3.000000e-09
GCST006011_68	Mean corpuscular volume	3.000000e-19
GCST007094_217	Diastolic blood pressure	4.000000e-08
GCST007102_14	Seasonality and depression	1.000000e-06
GCST007847_72	Type 2 diabetes	4.000000e-06
GCST008839_464	Height	1.000000e-08
GCST009375_8	Mosaic loss of chromosome Y (Y chromosome dosage)	5.000000e-16
GCST009379_61	Type 2 diabetes	6.000000e-09
GCST010002_340	Refractive error	5.000000e-12
GCST010244_370	Triglyceride levels	6.000000e-11
GCST90002384_55	Hemoglobin	2.000000e-10
GCST90002401_445	Platelet distribution width	3.000000e-14
GCST90014268_16	Cataracts	9.000000e-24

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0006995	response to diisocyanate
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0006336	diastolic blood pressure
EFO:0006876	seasonality measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004530	triglyceride measurement
EFO:0004509	hemoglobin measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression, decreases expression	3
Arsenic	affects methylation, decreases methylation, increases abundance, decreases expression	3
bisphenol A	increases expression	2
sodium arsenite	affects reaction, decreases expression, increases expression, decreases reaction, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
cupric chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	increases expression, affects cotreatment	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7Z1	Ubigene A-549 QKI KO	Cancer cell line	Male
CVCL_E0ME	Ubigene HeLa QKI KO	Cancer cell line	Female
CVCL_E1GN	Abcam U2OS QKI KO	Cancer cell line	Female
CVCL_TH89	HAP1 QKI (-) 1	Cancer cell line	Male
CVCL_XS06	HAP1 QKI (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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