HNRNPK

Summary

HNRNPK (heterogeneous nuclear ribonucleoprotein K, HGNC:5044) is a protein-coding gene on chromosome 9q21.32, encoding Heterogeneous nuclear ribonucleoprotein K (P61978). One of the major pre-mRNA-binding proteins. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progession. Several alternatively spliced transcript variants have been described for this gene, however, not all of them are fully characterized.

Source: NCBI Gene 3190 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 347 total — 32 pathogenic, 41 likely-pathogenic
• Phenotypes (HPO): 134
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 31 downstream targets (CollecTRI)
• MANE Select transcript: NM_031263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5044
Approved symbol	HNRNPK
Name	heterogeneous nuclear ribonucleoprotein K
Location	9q21.32
Locus type	gene with protein product
Status	Approved
Aliases	CSBP, TUNP
Ensembl gene	ENSG00000165119
Ensembl biotype	protein_coding
OMIM	600712
Entrez	3190

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 50 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000360384, ENST00000376256, ENST00000376263, ENST00000376281, ENST00000457156, ENST00000472778, ENST00000481820, ENST00000483135, ENST00000492865, ENST00000493362, ENST00000704004, ENST00000704005, ENST00000704006, ENST00000704007, ENST00000704008, ENST00000704009, ENST00000704010, ENST00000704011, ENST00000704012, ENST00000704013, ENST00000704014, ENST00000704015, ENST00000704016, ENST00000704051, ENST00000704052, ENST00000704053, ENST00000704054, ENST00000704055, ENST00000704056, ENST00000704057, ENST00000704058, ENST00000704059, ENST00000704060, ENST00000902585, ENST00000946123, ENST00000946124, ENST00000946125, ENST00000946126, ENST00000946127, ENST00000946128, ENST00000946129, ENST00000946130, ENST00000946131, ENST00000946132, ENST00000946133, ENST00000946134, ENST00000946135, ENST00000946136, ENST00000946137, ENST00000946138, ENST00000946139, ENST00000946140, ENST00000946141, ENST00000946142, ENST00000946143, ENST00000946144

RefSeq mRNA: 6 — MANE Select: NM_031263 NM_001318186, NM_001318187, NM_001318188, NM_002140, NM_031262, NM_031263

CCDS: CCDS6667, CCDS6668, CCDS94425, CCDS94426

Canonical transcript exons

ENST00000376263 — 17 exons

Exon	Start	End
ENSE00001272310	83978373	83978452
ENSE00001376875	83980153	83980215
ENSE00003478906	83977689	83977786
ENSE00003507975	83973902	83973973
ENSE00003543795	83972844	83972972
ENSE00003548317	83974517	83974589
ENSE00003596199	83973286	83973399
ENSE00003596401	83978195	83978279
ENSE00003660275	83970162	83970331
ENSE00003691931	83970737	83970819
ENSE00003890206	83975462	83975505
ENSE00003891081	83971882	83972189
ENSE00003891121	83970897	83970912
ENSE00003893453	83971672	83971726
ENSE00003893918	83971273	83971356
ENSE00003895588	83976995	83977051
ENSE00003990579	83968083	83969440

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 99.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 373.1390 / max 3816.0536, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101169	229.0489	1828
101171	138.9809	1825
101170	2.2314	1267
101165	1.2103	611
101164	1.0348	485
101163	0.3998	171
101162	0.2330	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.73	gold quality
calcaneal tendon	UBERON:0003701	99.73	gold quality
ganglionic eminence	UBERON:0004023	99.66	gold quality
cortical plate	UBERON:0005343	99.55	gold quality
monocyte	CL:0000576	99.46	gold quality
vermiform appendix	UBERON:0001154	99.46	gold quality
leukocyte	CL:0000738	99.45	gold quality
right uterine tube	UBERON:0001302	99.45	gold quality
smooth muscle tissue	UBERON:0001135	99.44	gold quality
left ovary	UBERON:0002119	99.39	gold quality
right lobe of thyroid gland	UBERON:0001119	99.38	gold quality
left lobe of thyroid gland	UBERON:0001120	99.38	gold quality
body of uterus	UBERON:0009853	99.38	gold quality
endocervix	UBERON:0000458	99.36	gold quality
right ovary	UBERON:0002118	99.36	gold quality
right lung	UBERON:0002167	99.35	gold quality
gall bladder	UBERON:0002110	99.34	gold quality
metanephros cortex	UBERON:0010533	99.34	gold quality
bone marrow cell	CL:0002092	99.33	gold quality
right adrenal gland cortex	UBERON:0035827	99.33	gold quality
right adrenal gland	UBERON:0001233	99.32	gold quality
left uterine tube	UBERON:0001303	99.32	gold quality
left adrenal gland	UBERON:0001234	99.29	gold quality
adrenal tissue	UBERON:0018303	99.29	gold quality
ectocervix	UBERON:0012249	99.28	gold quality
rectum	UBERON:0001052	99.27	gold quality
mucosa of stomach	UBERON:0001199	99.27	gold quality
skin of abdomen	UBERON:0001416	99.27	gold quality
adenohypophysis	UBERON:0002196	99.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.27	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	44.62
E-CURD-122	yes	16.64
E-MTAB-10042	yes	5.14
E-HCAD-10	no	35.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

31 targets.

Target	Regulation
AGT
AR
BGLAP
CDH2
CDKN1A
CNBP
EIF4E
EYA1
HNRNPK
INS
ITGAM
KL
LDLR
MAPK14
MYC
NOS2
OPRM1
ORM1
PCBP2
PCBP3
POT1
PPP1CC
PTBP1
PTGS2
SLC6A4
SPN
TP53
TPM1
TRIB3
VEGFA

Upstream regulators (CollecTRI, top): CNBP, FOXC1, HNRNPK, INS, SREBF1, TP53

miRNA regulators (miRDB)

90 targeting HNRNPK, 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-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-298	99.63	67.56	1916

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a component of an intronic splicing enhancer complex that activates the splicing of the alternative exon 6A from chicken beta-tropomyosin pre-mRNA. (PMID:11867641)
• c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs(hnRNPK) (PMID:12052863)
• hnRNP K KH3 specifically recognizes a tetrad of sequence 5’d-TCCC. The complex is stabilized by a dense network of methyl-oxygen hydrogen bonds involving the methyl groups of 3 isoleucine residues and the O2 and N3 atoms of the 2 central cytosine bases. (PMID:12093748)
• examination into mechanisms of hnRNP K activities by identifying protein factors that interact with it (PMID:12183465)
• we describe the identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a protein that specifically interacts with Sam68 in vitro and in vivo. (PMID:12370808)
• acts together with Pur(alpha) to repress the transcriptional activity of the CD43 gene promoter during lymphocyte activation (PMID:12411317)
• Nuclear shift of hnRNP K protein in dividing cells may reflect its involvement in signalling multiple events that regulate expression of genes in proliferating cells (PMID:14562022)
• Co-crystallization of the third KH domain of human hnRNP K with a 15-mer ssDNA showed that the crystals contained the complex containing three KH3 domains per 15-mer ssDNA (PMID:15039586)
• hnRNP K is a positive effector of collagen synthesis acting at the post-transcriptional level by interaction with the 3’-untranslated regions (3’-UTRs) of COL1A1, 1A2, and 3A1 mRNAs. (PMID:15514164)
• the mutually antagonistic action of two RNA-binding proteins, Hu and hnRNP K, control the timing of the switch from proliferation to neuronal differentiation through the post-transcriptional regulation of p21 mRNA (PMID:15671036)
• hnRNP K is involved in B cell receptor signalling pathway (PMID:15860232)
• NMR and X-ray crystallographic studies of the third KH domain of hnRNP K in complex with single-stranded nucleic acids (PMID:16004877)
• HNRPK down-regulation and interference with HNRPK translation-but not transcription-regulatory activity impairs proliferation, clonogenic potential, and leukemogenic activity of BCR/ABL-expressing myeloid 32Dcl3 and/or primary CD34+ CML-BC cells (PMID:16293596)
• Alternative isoform of hnRNPK found in colonic tumor and surrounding mucosa; is first example of RNA editing even in cancer and its surrounding tissue (PMID:16404425)
• arginine dimethylation of heterogeneous nuclear ribonucleoprotein K by protein-arginine methyltransferase 1 inhibits its interaction with c-Src (PMID:16492668)
• satellite I RNA binds to hnRNP K protein (PMID:16496041)
• These findings provide a putative mechanism by which transcriptional activity of hnRNP K can be discretely controlled through the regulation of PP1 activity. (PMID:16564677)
• Tandem mass-spectrometric analysis of the peptide at residues 288-303 of heterogeneous nuclear ribonucleoprotein K (hnRNP K) shows that both Arg296 and Arg299 are dimethylated. (PMID:17191129)
• Isolation of antibodies from cells with loss of migration phenotype and identification of their target proteins revealed the involvement of the heterogeneous nuclear ribonucleoprotein K (hnRNP-K), a multifunctional signaling protein, in metastasis (PMID:17483488)
• interacts with Sindbis virus NSP2 and viral subgenomic mRNA (PMID:17561226)
• Heterogeneous nuclear ribonucleoprotein K overexpression in oral squamous cell carcinoma. (PMID:17667925)
• APOBEC3 suppresses HBV replication in hepatocytes by inhibiting hnRNP K-mediated transcription and expression of HBV genes as well as HBV core DNA synthesis. (PMID:17672864)
• hnRNP K binds to the 3’-untranslated region of the c-Src mRNA and inhibits its translation by blocking 80 S ribosome formation (PMID:18441016)
• Inhibition of methylation in hnRNP K attenuated the recruitment of p53 to p21 promoter, and reduced p53 transcriptional activity. (PMID:18472002)
• Cytoplasmic hnRNP K and high thymidine phosphorylase may be potential prognostic and therapeutic markers for nasopharyngeal carcinoma. (PMID:18559600)
• The interaction of hnRNP-K with Nef strongly increased HIV transcription, which depended on Tat and the NF-kB motif in the viral promoter, but not on NF-kB activation. (PMID:18854243)
• HNRNP K and microRNA-16 have roles in cyclooxygenase-2 RNA stability induced by S100b, a ligand of the receptor for advanced glycation end products (PMID:18854308)
• Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and GRHL2 in human oral squamous cell carcinoma cells. (PMID:19015635)
• The data here provide possible mechanisms of how the non-enzymatic activity of PRMT family protein associates with hnRNP K protein and regulates hnRNP K protein-involved transactivation functions. (PMID:19101556)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• hnRNP K and RBM42 have a role in the maintenance of cellular ATP level in the stress conditions possibly through protecting their target mRNAs. (PMID:19170760)
• MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription (PMID:19249676)
• Translational inhibition of AR by hnRNP-K may occur in organ-confined tumors but possibly at a reduced level in metastases. HnRNP-K is the first protein identified that directly interacts with and regulates the AR translational apparatus. (PMID:19258514)
• Results collectively establish the regulation and role of ERK-mediated cytoplasmic accumulation of hnRNP K as an upstream modulator of TP, suggesting that hnRNP K may be an attractive candidate as a future therapeutic target for cancer. (PMID:19330019)
• hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in prostate cancer. (PMID:19401687)
• hnRNP K has a role in preventing the production of the pro-apoptotic Bcl-x(S) splice isoform (PMID:19520842)
• Cytoplasmic hnRNP K increased significantly from leukoplakia to head-and-neck/oral squamous cell carcinomas. (PMID:19548310)
• Data unveiled an important new signaling pathway that linked by hnRNP K and mutant p53 in pancreatic cancer tumorigenesis. (PMID:19609950)
• The overexpression of hnRNPK, which is regulated by BCR-ABL and Ras-MAPK signaling pathways, may promote the progression of CML. (PMID:19653139)
• proteolytically activated PKC-delta down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction (PMID:19747914)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hnrpkl	ENSDARG00000007034
danio_rerio	hnrnpk	ENSDARG00000018914
mus_musculus	Hnrnpk	ENSMUSG00000021546
rattus_norvegicus	Hnrnpk	ENSRNOG00000019113
drosophila_melanogaster	HnRNP-K	FBGN0267791
caenorhabditis_elegans	hrpk-1	WBGENE00017816

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein K — P61978 (reviewed: P61978)

Alternative names: Transformation up-regulated nuclear protein

All UniProt accessions (12): A0A994J4E9, A0A994J4S7, A0A994J4U9, A0A994J6T5, A0A994J6U9, A0A994J782, A0A994J795, B4DUQ1, P61978, Q5T6W2, S4R359, S4R457

UniProt curated annotations — full annotation on UniProt →

Function. One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction. As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation.

Subunit / interactions. Identified in the spliceosome C complex. Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, ZNF827 and HNRNPL. Interacts with RBM42 and ZIK1. Interacts with BRDT. Interacts with ANKRD28. Interacts with ASFV p30 protein. Interacts with DDX1. Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation. Interacts with p53/TP53. Interacts with IVNS1ABP (via BACK domain); the interaction is direct. Interacts with PPIA/CYPA. (Microbial infection) Interacts with HCV core protein.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm. Cell projection. Podosome.

Post-translational modifications. Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine. Sumoylated by CBX4. Sumoylation is increased upon DNA damage, such as that produced by doxorubicin, etoposide, UV light and camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under these conditions. Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination. O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.

Disease relevance. Au-Kline syndrome (AUKS) [MIM:616580] A disorder characterized by intellectual disability, facial dysmorphism, cardiac defects, and connective tissue and skeletal abnormalities. Dysmorphic features include long palpebral fissures, ptosis, a broad prominent nasal bridge, hypoplastic alae nasi, an open downturned mouth, ears with underdeveloped and thick helices, high palate, and a unique tongue with a prominent median crease. Hypotonia, hyporeflexia, and high pain tolerance are additional features. The disease is caused by variants affecting the gene represented in this entry.

Induction. By DNA damage, including ionizing radiations and phleomycin treatment or UV irradiation. This induction requires ATM kinase activity (ionizing radiations and phleomycin) or ATR activity (UV irradiation). Up-regulation is due to protein stabilization. Constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway.

Isoforms (3)

UniProt ID	Names	Canonical?
P61978-1	1	yes
P61978-2	2
P61978-3	3

RefSeq proteins (6): NP_001305115, NP_001305116, NP_001305117, NP_002131, NP_112552, NP_112553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR012987	ROK_N	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013, PF08067

UniProt features (68 total): modified residue 17, cross-link 11, repeat 9, region of interest 9, helix 5, strand 4, domain 3, compositionally biased region 3, splice variant 2, mutagenesis site 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
1ZZK	X-RAY DIFFRACTION	0.95
7RJO	X-RAY DIFFRACTION	1.38
1ZZI	X-RAY DIFFRACTION	1.8
7RJK	X-RAY DIFFRACTION	1.85
1ZZJ	X-RAY DIFFRACTION	2.3
7CRU	X-RAY DIFFRACTION	2.8
7CRE	X-RAY DIFFRACTION	3
1J5K	SOLUTION NMR
1KHM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61978-F1	64.22	0.08

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 (28): 1, 34, 36, 39, 75, 116, 198, 214, 216, 219, 284, 316, 377, 379, 380, 405, 420, 34, 34, 52 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
422	loss of sumoylation. loss of tp53 transcriptional stimulation.
424	loss of sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9610379	HCMV Late Events
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 605 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, YAGI_AML_WITH_INV_16_TRANSLOCATION, MORF_SNRP70, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, HSIAO_HOUSEKEEPING_GENES, GGGTGGRR_PAX4_03, GGCNKCCATNK_UNKNOWN, GOBP_LOW_DENSITY_LIPOPROTEIN_PARTICLE_CLEARANCE, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, MORF_TERF1, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, MUELLER_PLURINET

GO Biological Process (19): mRNA splicing, via spliceosome (GO:0000398), regulation of transcription by RNA polymerase II (GO:0006357), RNA processing (GO:0006396), signal transduction (GO:0007165), regulatory ncRNA-mediated heterochromatin formation (GO:0031048), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of mRNA splicing, via spliceosome (GO:0048024), negative regulation of mRNA splicing, via spliceosome (GO:0048025), random inactivation of X chromosome (GO:0060816), regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902165), positive regulation of low-density lipoprotein particle clearance (GO:1905581), regulation of DNA-templated transcription (GO:0006355), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of gene expression (GO:0010629), regulation of apoptotic process (GO:0042981), negative regulation of RNA metabolic process (GO:0051253)

GO Molecular Function (8): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), cadherin binding (GO:0045296), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (14): chromatin (GO:0000785), podosome (GO:0002102), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), focal adhesion (GO:0005925), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904), spliceosomal complex (GO:0005681), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
mRNA Splicing	1
Metabolism of RNA	1
HCMV Infection	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
gene expression	2
apoptotic process	2
DNA-templated transcription	2
mRNA splicing, via spliceosome	2
regulation of gene expression	2
RNA processing	2
nucleic acid binding	2
protein binding	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA biosynthetic process	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulatory ncRNA-mediated gene silencing	1
heterochromatin formation	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
regulation of RNA splicing	1
regulation of mRNA processing	1
negative regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
negative regulation of mRNA processing	1
dosage compensation by inactivation of X chromosome	1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1

Protein interactions and networks

STRING

3884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPK	NUCLEOLIN	P19338	986
HNRNPK	PTBP1	P26599	974
HNRNPK	PUF60	Q9UHX1	967
HNRNPK	FXR2	P51116	954
HNRNPK	SF3B3	Q15393	935
HNRNPK	RBM42	Q9BTD8	930
HNRNPK	FXR1	P51114	923
HNRNPK	PCBP1	Q15365	912
HNRNPK	NSUN3	Q9H649	890
HNRNPK	KCNG1	Q9UIX4	882
HNRNPK	SPI1	P17947	879
HNRNPK	GATA1	P15976	878
HNRNPK	KHDRBS1	Q07666	867
HNRNPK	ABI1	Q8IZP0	857
HNRNPK	HNRNPC	P07910	856

IntAct

580 interactions, top by confidence:

A	B	Type	Score
HNRNPK	GRB2	psi-mi:“MI:0915”(physical association)	0.850
GRB2	HNRNPK	psi-mi:“MI:0915”(physical association)	0.850
HNRNPK	QKI	psi-mi:“MI:0915”(physical association)	0.820
QKI	HNRNPK	psi-mi:“MI:0915”(physical association)	0.820
RBMX	HNRNPK	psi-mi:“MI:0915”(physical association)	0.800
HNRNPK	RBMX	psi-mi:“MI:0915”(physical association)	0.800
CIRBP	HNRNPK	psi-mi:“MI:0915”(physical association)	0.800
HNRNPK	CIRBP	psi-mi:“MI:0915”(physical association)	0.800
HNRNPK	HNRNPK	psi-mi:“MI:0915”(physical association)	0.750
PRR3	HNRNPK	psi-mi:“MI:0915”(physical association)	0.740
HNRNPK	PRR3	psi-mi:“MI:0915”(physical association)	0.740
SNRPA	HNRNPK	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (1118): HNRNPK (Affinity Capture-MS), HNRNPK (Affinity Capture-MS), HNRNPK (Affinity Capture-MS), HNRNPK (Two-hybrid), HNRNPK (Two-hybrid), HNRNPK (Two-hybrid), HNRNPK (Two-hybrid), HNRNPK (Two-hybrid), RBM3 (Two-hybrid), RBMY1A1 (Two-hybrid), SNRPA (Two-hybrid), SPG7 (Two-hybrid), TYK2 (Two-hybrid), U2AF1 (Two-hybrid), QKI (Two-hybrid)

ESM2 similar proteins: A0A0D1DZT6, A6R3L3, A7VJC2, B7FAL5, D0VWM8, O19049, O88569, P0CO44, P0CO45, P17130, P21522, P22626, P25555, P38922, P51990, P61978, P61979, P61980, P78814, P92964, P98179, Q01560, Q09911, Q13151, Q14498, Q15056, Q1JPH6, Q28521, Q2HJ60, Q2QKB3, Q32P51, Q3T0D0, Q4R4M6, Q4WXV6, Q5R5H8, Q5RBR8, Q5RBU8, Q5RC80, Q5XI72, Q7KMJ6

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O19048, O19049, O73932, O74919, P51513, P57721, P57722, P60335, P61978, P61979, P61980, Q15365, Q15366, Q2PFW9, Q32PX7, Q3T0D0, Q4R4M6, Q5E9A3, Q5R5H8, Q5RB68, Q5SF07, Q5ZIQ3, Q5ZLP8, Q61990, Q80WA4, Q8UVD9, Q91WJ8, Q96AE4, Q96I24, Q9JKN6, Q9LZ82, Q9SZH4, Q9UNW9, Q9Y6M1, F4KDN0, Q80VL1, Q9Y2W6, A6NAF9

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
MAPK3	“down-regulates activity”	HNRNPK	phosphorylation
MAPK8	“up-regulates activity”	HNRNPK	phosphorylation
ERK1/2	up-regulates	HNRNPK	phosphorylation
JNK	up-regulates	HNRNPK	phosphorylation
MAPK8	up-regulates	HNRNPK	phosphorylation
MAPK3	down-regulates	HNRNPK	phosphorylation
MAPK10	“up-regulates activity”	HNRNPK	phosphorylation
PRKCD	unknown	HNRNPK	phosphorylation
PRKCD	down-regulates	HNRNPK	phosphorylation
SRC	down-regulates	HNRNPK	phosphorylation
MAPK10	“down-regulates activity”	HNRNPK	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Packaging Of Telomere Ends	5	20.3×	5e-04
Recognition and association of DNA glycosylase with site containing an affected purine	5	18.9×	5e-04
Cleavage of the damaged purine	5	18.9×	5e-04
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	17.1×	6e-04
Cleavage of the damaged pyrimidine	5	17.1×	6e-04
Inhibition of DNA recombination at telomere	5	15.6×	7e-04
DNA Damage/Telomere Stress Induced Senescence	5	15.1×	8e-04
Regulation of PD-L1(CD274) transcription	7	14.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of mRNA splicing, via spliceosome	5	38.8×	3e-05
regulation of alternative mRNA splicing, via spliceosome	6	20.9×	6e-05
positive regulation of translation	5	16.3×	1e-03
mRNA splicing, via spliceosome	12	15.7×	7e-09
mRNA processing	10	11.2×	5e-06
RNA splicing	7	8.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	41
Uncertain significance	104
Likely benign	90
Benign	47

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029561	NM_031263.4(HNRNPK):c.573_574del (p.Arg191fs)	Pathogenic
1204941	NM_031263.4(HNRNPK):c.431_434del (p.Asp144fs)	Pathogenic
1685880	NM_031263.4(HNRNPK):c.1240C>T (p.Arg414Cys)	Pathogenic
1706529	NM_031263.4(HNRNPK):c.1040_1041del (p.Ser347fs)	Pathogenic
1706586	NM_031263.4(HNRNPK):c.402+1G>A	Pathogenic
1708495	NM_031263.4(HNRNPK):c.1048_1051del (p.Asp350fs)	Pathogenic
1803038	NM_031263.4(HNRNPK):c.1192-7_1192-3del	Pathogenic
1805748	NM_031263.4(HNRNPK):c.440T>A (p.Leu147Ter)	Pathogenic
212775	NM_031263.4(HNRNPK):c.953+1dup	Pathogenic
221225	NM_031263.4(HNRNPK):c.931_932insTT (p.Pro311fs)	Pathogenic
2499094	NM_031263.4(HNRNPK):c.950_953+1dup	Pathogenic
2501876	NM_031263.4(HNRNPK):c.1108+1G>T	Pathogenic
2573160	NM_031263.4(HNRNPK):c.1361+1G>A	Pathogenic
2573161	NM_031263.4(HNRNPK):c.257+5G>A	Pathogenic
2631194	NM_031263.4(HNRNPK):c.1053_1054dup (p.Trp352fs)	Pathogenic
280639	NM_031263.4(HNRNPK):c.779dup (p.Phe261_Asp262insTer)	Pathogenic
280716	NM_031263.4(HNRNPK):c.1250C>A (p.Ser417Ter)	Pathogenic
2852514	NM_031263.4(HNRNPK):c.1240del (p.Arg414fs)	Pathogenic
3238832	NM_031263.4(HNRNPK):c.1093-2A>C	Pathogenic
3254786	NM_031263.4(HNRNPK):c.1122_1123insT (p.Gly375fs)	Pathogenic
3340918	NM_031263.4(HNRNPK):c.214-13A>G	Pathogenic
3764099	NM_031263.4(HNRNPK):c.1074dup (p.Met359fs)	Pathogenic
3899365	NM_031263.4(HNRNPK):c.504_507del (p.Lys168fs)	Pathogenic
449308	NM_031263.4(HNRNPK):c.1008+1G>A	Pathogenic
503601	NM_031263.4(HNRNPK):c.998dup (p.Tyr333Ter)	Pathogenic
503602	NM_002140.4(HNRNPK):c.1009delG	Pathogenic
503603	NM_031263.4(HNRNPK):c.859C>T (p.Arg287Ter)	Pathogenic
503604	NM_002140.4(HNRNPK):c.1094delG	Pathogenic
625163	NM_031263.4(HNRNPK):c.464T>C (p.Leu155Pro)	Pathogenic
931166	NM_031263.4(HNRNPK):c.1192-14_1192-2del	Pathogenic

SpliceAI

2108 predictions. Top by Δscore:

Variant	Effect	Δscore
9:83969439:CA:C	acceptor_gain	1.0000
9:83969441:C:CC	acceptor_gain	1.0000
9:83970157:CTGA:C	donor_loss	1.0000
9:83970158:TGACC:T	donor_loss	1.0000
9:83970159:GACC:G	donor_loss	1.0000
9:83970161:C:CA	donor_loss	1.0000
9:83970327:GCCAA:G	acceptor_gain	1.0000
9:83970328:CCAA:C	acceptor_gain	1.0000
9:83970328:CCAAC:C	acceptor_gain	1.0000
9:83970329:CAA:C	acceptor_gain	1.0000
9:83970329:CAAC:C	acceptor_gain	1.0000
9:83970330:A:T	acceptor_gain	1.0000
9:83970330:AA:A	acceptor_gain	1.0000
9:83970330:AACTG:A	acceptor_loss	1.0000
9:83970331:ACT:A	acceptor_loss	1.0000
9:83970332:C:CC	acceptor_gain	1.0000
9:83970735:A:AC	donor_gain	1.0000
9:83970735:ACAT:A	donor_gain	1.0000
9:83970736:C:CC	donor_gain	1.0000
9:83970736:CA:C	donor_gain	1.0000
9:83970736:CAT:C	donor_gain	1.0000
9:83970736:CATC:C	donor_gain	1.0000
9:83970736:CATCT:C	donor_gain	1.0000
9:83970801:CCCC:C	acceptor_gain	1.0000
9:83970802:CCCC:C	acceptor_gain	1.0000
9:83970911:CC:C	acceptor_gain	1.0000
9:83970912:CC:C	acceptor_gain	1.0000
9:83970913:C:CC	acceptor_gain	1.0000
9:83971270:AAC:A	donor_gain	1.0000
9:83971271:A:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000395912 (9:83976879 T>A,C), RS1000400170 (9:83972498 G>A), RS1000539971 (9:83980362 T>A,C,G), RS1000616043 (9:83975822 A>G,T), RS1000731898 (9:83975219 G>A), RS1000770983 (9:83972746 A>T), RS1000911319 (9:83980510 C>A), RS1000927795 (9:83977464 TCTC>T), RS1000958763 (9:83977207 A>G), RS1001106953 (9:83981167 A>G), RS1001502783 (9:83977402 C>T), RS1001618946 (9:83977154 T>C), RS1001628857 (9:83979375 T>C), RS1001804673 (9:83968812 G>A), RS1001828498 (9:83976365 T>C)

Disease associations

OMIM: gene MIM:600712 | disease phenotypes: MIM:604916, MIM:616580

GenCC curated gene-disease

Disease	Classification	Inheritance
Au-Kline syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome	Definitive	AD

Mondo (3): Au-Kline syndrome (MONDO:0014700), cleft lip/palate (MONDO:0016044), intellectual disability (MONDO:0001071)

Orphanet (5): Okamoto syndrome (Orphanet:2729), Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome (Orphanet:453499), Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to a point mutation (Orphanet:453504), Cleft lip/palate (Orphanet:199306), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

134 total (30 of 134 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000126	Hydronephrosis
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000341	Narrow forehead
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000456	Bifid nasal tip
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000586	Shallow orbits

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST007294_144	Body fat distribution (trunk fat ratio)	5.000000e-19
GCST007294_83	Body fat distribution (trunk fat ratio)	7.000000e-17
GCST007295_107	Body fat distribution (leg fat ratio)	2.000000e-13
GCST007295_11	Body fat distribution (leg fat ratio)	2.000000e-06
GCST007295_92	Body fat distribution (leg fat ratio)	6.000000e-18
GCST010244_226	Triglyceride levels	6.000000e-19
GCST90002388_222	Lymphocyte count	4.000000e-22
GCST90002400_376	Plateletcrit	1.000000e-12
GCST90002402_62	Platelet count	3.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004530	triglyceride measurement
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C565736	Hydronephrosis, Congenital, with Cleft Palate, Characteristic Facies, Hypotonia, and Mental Retardation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3469 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56.37	nM	CHEMBL3752910
7.25	ED50	56.37	nM	CHEMBL3752910
6.74	Kd	184.2	nM	CHEMBL5653589
6.74	ED50	184.2	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148533: Binding affinity to human HNRNPK incubated for 45 mins by Kinobead based pull down assay	kd	0.0564	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148533: Binding affinity to human HNRNPK incubated for 45 mins by Kinobead based pull down assay	kd	0.1842	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression, decreases expression	3
(+)-JQ1 compound	decreases expression, affects binding	2
Ethanol	increases abundance, increases expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, affects cotreatment, increases expression	2
Caffeine	affects phosphorylation, increases expression	2
Doxorubicin	decreases expression, decreases response to substance	2
Tobacco Smoke Pollution	increases expression, affects expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
9-hydroxyoctadecadienoic acid	increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
withaferin A	affects cotreatment, decreases expression, affects binding, decreases activity	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
5-chloro-2-methyl-4-isothiazolin-3-one	increases metabolic processing	1
trichostatin A	affects expression	1
cinnamaldehyde	increases metabolic processing	1
beta-lapachone	decreases expression	1
sulforaphane	affects binding	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
bufalin	decreases expression	1
perfluorooctanoic acid	increases expression	1
coumarin	affects phosphorylation	1
cupric oxide	increases phosphorylation	1
artenimol	affects binding	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651575	Binding	Binding affinity to human HNRNPK incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06408337	PHASE1/PHASE2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate