NKRF

Summary

NKRF (NFKB repressing factor, HGNC:19374) is a protein-coding gene on chromosome Xq24, encoding NF-kappa-B-repressing factor (O15226). Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15.

This gene encodes a transcriptional repressor that interacts with specific negative regulatory elements to mediate transcriptional repression of certain nuclear factor kappa B responsive genes. The protein localizes predominantly to the nucleolus with a small fraction found in the nucleoplasm and cytoplasm. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 55922 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 87 total — 2 pathogenic
• Druggable target: yes
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_001417890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19374
Approved symbol	NKRF
Name	NFKB repressing factor
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	XTBD3, ITBA4, NRF
Ensembl gene	ENSG00000186416
Ensembl biotype	protein_coding
OMIM	300440
Entrez	55922

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000304449, ENST00000487600, ENST00000542113, ENST00000649446, ENST00000688521

RefSeq mRNA: 1 — MANE Select: NM_001417890 NM_001417890

Canonical transcript exons

ENST00000688521 — 4 exons

Exon	Start	End
ENSE00003581481	119592383	119592513
ENSE00003927504	119605731	119605961
ENSE00003931765	119605964	119605995
ENSE00003935934	119589352	119591309

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 89.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9151 / max 97.3772, expressed in 1801 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200287	15.7017	1795
200284	0.9363	252
200283	0.5983	176
200285	0.3207	157
200286	0.2595	109
200288	0.0986	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
postcentral gyrus	UBERON:0002581	89.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.00	gold quality
parietal lobe	UBERON:0001872	88.37	silver quality
superior frontal gyrus	UBERON:0002661	88.14	gold quality
middle temporal gyrus	UBERON:0002771	87.73	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.64	gold quality
entorhinal cortex	UBERON:0002728	87.36	silver quality
primary visual cortex	UBERON:0002436	85.91	gold quality
cortical plate	UBERON:0005343	85.77	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.67	silver quality
pons	UBERON:0000988	85.28	gold quality
prefrontal cortex	UBERON:0000451	85.17	gold quality
occipital lobe	UBERON:0002021	84.62	gold quality
frontal cortex	UBERON:0001870	84.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.22	gold quality
orbitofrontal cortex	UBERON:0004167	84.12	gold quality
neocortex	UBERON:0001950	84.10	gold quality
cerebral cortex	UBERON:0000956	83.82	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.38	silver quality
hypothalamus	UBERON:0001898	83.12	gold quality
ganglionic eminence	UBERON:0004023	83.11	gold quality
right frontal lobe	UBERON:0002810	82.58	gold quality
superior vestibular nucleus	UBERON:0007227	82.56	silver quality
cingulate cortex	UBERON:0003027	82.33	gold quality
telencephalon	UBERON:0001893	82.32	gold quality
anterior cingulate cortex	UBERON:0009835	82.24	gold quality
temporal lobe	UBERON:0001871	81.85	gold quality
forebrain	UBERON:0001890	81.78	gold quality
substantia nigra pars compacta	UBERON:0001965	81.77	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
ABCC8
CXCL8	Activation
GCLC
GCLM
HPGDS
HSPA9
IFNB1	Activation
NFKB
NOS2
PTGS2
SERPINA1

miRNA regulators (miRDB)

61 targeting NKRF, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-497-3P	99.61	69.71	1990

Literature-anchored findings (GeneRIF, showing 22)

• role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene (PMID:12381793)
• cDNA is 3247 bp long, contains three exons and maps to human chromosome Xq24. NRF is widely expressed in human tissues. (PMID:14744032)
• Full-length NRF is highly enriched in nucleoli and only a small fraction of NRF is found in the nucleoplasm and cytoplasm (PMID:15226370)
• NRF interrupts the regulatory coupling of LTR binding factors and transcription elongation events; this inhibitory mechanism might contribute to transcriptional quiescence of integrated HIV-1 provirus (PMID:16107696)
• Induction of MMP-9 gene expression is regulated by oscillatory/cumulative activation of NFkappaB in a colon cancer cell line. (PMID:17186550)
• The data of this study show that JKTBP1 and the 14-nt element act independently to mediate NRF internal ribosome entry segment activity. (PMID:17592041)
• saimiri transformation-associated protein of subgroup C induces NF-kappaB activation (PMID:18560378)
• Induction of NRF in human airway smooth muscle cells by neutrophil elastase mediates the suppression of interleukin (IL)-8/CXCL8 expression. (PMID:19542452)
• The results indicate that JKTBP1 regulates the level of NRF protein expression by binding to both NRF 5’ and 3’ UTRs. (PMID:21300069)
• The expression of NKRF is decreased in PBMCs of patients with stable COPD. The downregulation of NKRF was found to be closely related to enhanced IL-8 production from these peripheral blood cells through de-repression of the IL-8 promoter. (PMID:22441735)
• NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high. (PMID:24223729)
• The up-regulated NKRF serves as an endogenous repressor for IP-10 and IL-8 synthesis to hinder host from robust response to MTb infection. (PMID:25135111)
• MIR29 targets and reduces expression of CLDN1 and NKRF to increase intestinal permeability in inflammatory bowel disease. (PMID:25277410)
• NF-kappaB-repressing factor (NKRF) phosphorylation modulates promoter-proximal transcription elongation of NF-kappaB/NKRF-regulated genes via direct interactions with elongation complex in response to specific stimuli (PMID:26340924)
• NKRF is a nucleolar HSP essential for nucleolus homeostasis and cell survival under proteotoxic stress. NKRF is a thermosensor translocating from the nucleolus to the nucleoplasm during heat stress; nucleolar pools are replenished upon HSF1-mediated NKRF resynthesis. NKRF is an unconventional HSP crucial for correct rRNA processing. Under stress conditions, NKRF directs XRN2 nucleolus/nucleoplasm trafficking. (PMID:28096332)
• depletion of NKRF, XRN2 or DHX15 impairs an early pre-rRNA cleavage step. (PMID:28115624)
• Data suggest that L protein from LCMV interactions with host proteome, specifically DDX3X, NKRF, and TRIM21. (LCMV = Lymphocytic choriomeningitis mammarenavirus; DDX3X = DEAD-box helicase 3; NKRF = NF-kappa-B-repressing factor; TRIM21 = tripartite motif-containing protein-21) (PMID:29261807)
• Low NRF expression is associated with obesity induced nephropathy. (PMID:30729676)
• RNA affinity, helicase, and ATPase activity of DHX15 are increased when the G-patch motif of NKRF binds in an extended conformation across the helicase surface (PMID:32179686)
• Upregulation of miRNA301a3p promotes tumor progression in gastric cancer by suppressing NKRF and activating NFkappaB signaling. (PMID:32468020)
• WWP2 binds to NKRF, enhances the NF-kappaB signaling, and promotes malignant phenotypes of acute myeloid leukemia cells. (PMID:37921219)
• A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-beta Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells. (PMID:38612387)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkrf	ENSDARG00000100536
mus_musculus	Nkrf	ENSMUSG00000044149
rattus_norvegicus	Nkrf	ENSRNOG00000061989
drosophila_melanogaster	CG31301	FBGN0051301
caenorhabditis_elegans	paxt-1	WBGENE00011034

Paralogs (2): CDKN2AIP (ENSG00000168564), CDKN2AIPNL (ENSG00000237190)

Protein

Protein identifiers

NF-kappa-B-repressing factor — O15226 (reviewed: O15226)

Alternative names: Protein ITBA4

All UniProt accessions (3): A0A8I5KX72, A3F769, O15226

UniProt curated annotations — full annotation on UniProt →

Function. Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15. Involved in the constitutive silencing of the interferon beta promoter, independently of the virus-induced signals, and in the inhibition of the basal and cytokine-induced iNOS promoter activity. Also involved in the regulation of IL-8 transcription. May also act as a DNA-binding transcription regulator: interacts with a specific negative regulatory element (NRE) 5’-AATTCCTCTGA-3’ to mediate transcriptional repression of certain NK-kappa-B responsive genes.

Subunit / interactions. Interacts with NF-kappa-B. Interacts with XRN2. Interacts (via G-patch domain) with DHX15; promoting the RNA helicase activity of DHX15.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Widely and constitutively expressed. Expressed at lower level in colon, peripheral blood lymphocytes, lung and kidney.

Isoforms (2)

UniProt ID	Names	Canonical?
O15226-1	1	yes
O15226-2	2

RefSeq proteins (1): NP_001404819* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000467	G_patch_dom	Domain
IPR001374	R3H_dom	Domain
IPR014720	dsRBD_dom	Domain
IPR034071	R3H_NRF	Domain
IPR036867	R3H_dom_sf	Homologous_superfamily
IPR058828	DSRM_CARF/NKRF	Domain

Pfam: PF01424, PF01585, PF26535

UniProt features (29 total): mutagenesis site 6, cross-link 4, region of interest 4, sequence conflict 3, domain 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1, helix 1, strand 1, turn 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6SH6	X-RAY DIFFRACTION	1.85
6SH7	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15226-F1	70.14	0.30

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 (5): 618, 68, 500, 666, 674

Mutagenesis-validated functional residues (6):

Position	Phenotype
555	abolished interaction with dhx15.
559	abolished interaction with dhx15.
564	abolished interaction with dhx15.
569	abolished interaction with dhx15.
590	decreased, but not abolished interaction, with dhx15.
591	decreased, but not abolished interaction, with dhx15.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MORF_MSH3, MORF_BRCA1, MORF_ATRX, GTGCCTT_MIR506, MODULE_120, CATTTCA_MIR203, MORF_PPP5C, MORF_FANCG, MORF_RAP1A, CTTTGTA_MIR524, GOCC_NUCLEOLUS, WORSCHECH_TUMOR_REJECTION_UP, GOMF_ATPASE_ACTIVATOR_ACTIVITY, GEORGES_TARGETS_OF_MIR192_AND_MIR215

GO Biological Process (2): negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), ATPase activator activity (GO:0001671), RNA binding (GO:0003723), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nucleic acid binding	2
binding	2
nuclear lumen	2
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
ATP-dependent activity	1
molecular function activator activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKRF	KEAP1	Q14145	888
NKRF	JUN	P05412	767
NKRF	POU2F3	Q9UKI9	718
NKRF	DCAF11	Q8TEB1	693
NKRF	RELA	Q04206	690
NKRF	MAF	O75444	653
NKRF	HMOX1	P09601	600
NKRF	NFE2L3	Q9Y4A8	586
NKRF	NOC2L	Q9Y3T9	579
NKRF	XRN2	Q9H0D6	578
NKRF	NFE2	Q16621	549
NKRF	NFE2L2	Q16236	548
NKRF	CPSF4	O95639	540
NKRF	FOS	P01100	525
NKRF	NQO1	P15559	506

IntAct

240 interactions, top by confidence:

A	B	Type	Score
NKRF	PRKRA	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NKRF	DHX15	psi-mi:“MI:0915”(physical association)	0.670
NKRF	ZNF346	psi-mi:“MI:0915”(physical association)	0.670
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
NKRF	STAU1	psi-mi:“MI:0915”(physical association)	0.560
NKRF	ADARB1	psi-mi:“MI:0915”(physical association)	0.560
N	NKRF	psi-mi:“MI:0915”(physical association)	0.560
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0915”(physical association)	0.500
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
JUN	NKRF	psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
NKRF	HNRNPA1L2	psi-mi:“MI:0915”(physical association)	0.400
NKRF	NS	psi-mi:“MI:0915”(physical association)	0.370
NKRF	NS1	psi-mi:“MI:0915”(physical association)	0.370
NS1	NKRF	psi-mi:“MI:0915”(physical association)	0.370
NS	NKRF	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (316): NKRF (Affinity Capture-RNA), NKRF (Affinity Capture-RNA), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Proximity Label-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS), NKRF (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN38, A3EX96, A5DK05, A7E2Z2, A8MQG7, B1H2Q2, D0Z5N4, F4JJE0, G5EEW9, G5EFD2, H2KY84, O01326, O01767, O15226, O45523, O74975, P0C530, P21081, P21605, P33863, P34541, Q03615, Q04688, Q06651, Q08BS4, Q10024, Q177G4, Q18008, Q18317, Q1A173, Q21341, Q28D84, Q4V863, Q5ICL9, Q5SVQ0, Q66HD5, Q6E3F0, Q6E3F2, Q6NUB7, Q8BY02

Diamond homologs: A0A0R4IEW8, A4FV72, A4RHN3, A5A6M3, A5E1Z4, A6NDE4, A6NEQ0, A7SKE9, D4AE41, F4JCU0, O02008, O15226, O75526, O89086, O93235, P0C7P1, P0C8Z4, P0CB38, P0DJD3, P0DJD4, P10979, P19018, P31209, P38159, P39697, P41891, P60824, P60825, P60826, P62995, P62996, P62997, P84586, P98179, Q03251, Q03878, Q05196, Q09511, Q0U1G2, Q10422

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NKRF	“down-regulates quantity by repression”	IFNB1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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
Peptide chain elongation	23	23.0×	7e-24
Viral mRNA Translation	23	23.0×	7e-24
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	22.7×	9e-24
Eukaryotic Translation Termination	24	22.7×	2e-24
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	24	22.2×	2e-24
Selenocysteine synthesis	23	21.8×	2e-23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	23	21.3×	3e-23
SRP-dependent cotranslational protein targeting to membrane	26	20.5×	3e-25

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	26	28.5×	3e-28
regulation of mRNA processing	5	26.2×	8e-05
NLS-bearing protein import into nucleus	5	23.7×	1e-04
alternative mRNA splicing, via spliceosome	5	19.9×	3e-04
ribosomal large subunit biogenesis	7	18.4×	1e-05
positive regulation of viral genome replication	5	17.2×	5e-04
translation	27	16.4×	1e-22
regulation of alternative mRNA splicing, via spliceosome	11	15.9×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	45
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2579183	GRCh38/hg38 Xq24(chrX:119582581-119589158)x0	Pathogenic
984429	GRCh37/hg19 Xq24(chrX:118679335-118744405)x0	Pathogenic

SpliceAI

391 predictions. Top by Δscore:

Variant	Effect	Δscore
X:119592377:ACTC:A	donor_loss	1.0000
X:119592378:CTCA:C	donor_loss	1.0000
X:119592379:TCA:T	donor_loss	1.0000
X:119592380:CA:C	donor_loss	1.0000
X:119592381:A:AC	donor_gain	1.0000
X:119592381:AC:A	donor_gain	1.0000
X:119592382:C:CC	donor_gain	1.0000
X:119592382:CC:C	donor_gain	1.0000
X:119592382:CCAT:C	donor_gain	1.0000
X:119592381:ACCAT:A	donor_gain	0.9900
X:119592382:CCATC:C	donor_gain	0.9900
X:119592376:TACT:T	donor_loss	0.9800
X:119591307:GACCT:G	acceptor_loss	0.9700
X:119591308:ACCT:A	acceptor_loss	0.9700
X:119591311:T:A	acceptor_loss	0.9700
X:119593096:TACAA:T	donor_gain	0.9700
X:119593097:ACAAA:A	donor_gain	0.9700
X:119593098:CAAA:C	donor_gain	0.9700
X:119593098:CAAAC:C	donor_gain	0.9700
X:119591838:C:CC	acceptor_gain	0.9600
X:119592382:CCA:C	donor_gain	0.9600
X:119592515:T:G	acceptor_loss	0.9600
X:119592518:T:C	acceptor_gain	0.9600
X:119593097:A:AC	donor_gain	0.9600
X:119593098:C:CC	donor_gain	0.9600
X:119592512:ACCT:A	acceptor_gain	0.9500
X:119593091:ATAC:A	donor_loss	0.9400
X:119593092:TACT:T	donor_loss	0.9400
X:119593093:ACT:A	donor_loss	0.9400
X:119593094:CTTA:C	donor_loss	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000043587 (X:119600451 G>A), RS1000352141 (X:119608287 G>A,T), RS1000538369 (X:119589136 A>G), RS1000596210 (X:119604545 T>C), RS1000898079 (X:119601171 T>A), RS1001021611 (X:119592214 A>G), RS1001075468 (X:119591732 C>G), RS1001385472 (X:119606861 A>C), RS1001962004 (X:119592904 G>A,C), RS1002081262 (X:119588563 G>A), RS1002540593 (X:119594425 A>T), RS1002561695 (X:119596339 G>A), RS1002592228 (X:119604967 C>G), RS1003078824 (X:119593626 G>A), RS1003189158 (X:119597405 TGGTTATGAC>T)

Disease associations

OMIM: gene MIM:300440 | disease phenotypes: MIM:300860

GenCC curated gene-disease

Mondo (1): syndromic X-linked intellectual disability Nascimento type (MONDO:0010461)

Orphanet (1): X-linked intellectual disability, Nascimento type (Orphanet:163956)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3163 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
deoxynivalenol	increases expression	1
arsenite	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	decreases phosphorylation	1
nivalenol	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Melphalan	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL752722	Binding	Inhibition of DNA binding of NF-uM) PMA/PHA activated Jurkat cells; No significant inhibition	Inhibition of cytokine production by hymenialdisine derivatives. — J Med Chem

Clinical trials (associated diseases)

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