KHSRP

Summary

KHSRP (KH-type splicing regulatory protein, HGNC:6316) is a protein-coding gene on chromosome 19p13.3, encoding Far upstream element-binding protein 2 (Q92945). Binds to the dendritic targeting element and may play a role in mRNA trafficking. It is a selective cancer dependency (DepMap: 11.8% of cell lines).

The KHSRP gene encodes a multifunctional RNA-binding protein implicated in a variety of cellular processes, including transcription, alternative pre-mRNA splicing, and mRNA localization (Min et al., 1997 [PubMed 9136930]; Gherzi et al., 2004 [PubMed 15175153]).

Source: NCBI Gene 8570 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy, childhood-onset, remitting (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 166 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• MANE Select transcript: NM_001366299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6316
Approved symbol	KHSRP
Name	KH-type splicing regulatory protein
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KSRP, FBP2, FUBP2
Ensembl gene	ENSG00000088247
Ensembl biotype	protein_coding
OMIM	603445
Entrez	8570

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 retained_intron

ENST00000398148, ENST00000594496, ENST00000594745, ENST00000595112, ENST00000595223, ENST00000595258, ENST00000595548, ENST00000597656, ENST00000597704, ENST00000599395, ENST00000599642, ENST00000600480

RefSeq mRNA: 3 — MANE Select: NM_001366299 NM_001366299, NM_001366300, NM_003685

CCDS: CCDS45936, CCDS92499

Canonical transcript exons

ENST00000600480 — 19 exons

Exon	Start	End
ENSE00001060055	6415380	6415457
ENSE00001160174	6415534	6415734
ENSE00001160181	6415808	6415896
ENSE00001160189	6416298	6416407
ENSE00001160198	6416490	6416650
ENSE00001160204	6416738	6416882
ENSE00001160213	6416987	6417087
ENSE00002992266	6413102	6415301
ENSE00003471725	6420073	6420144
ENSE00003547088	6421650	6421688
ENSE00003556339	6420422	6420471
ENSE00003558586	6421278	6421317
ENSE00003610219	6418483	6418581
ENSE00003660721	6419203	6419260
ENSE00003661159	6418702	6418876
ENSE00003678451	6417981	6418079
ENSE00003679561	6422340	6422436
ENSE00003784701	6417739	6417841
ENSE00003915274	6424453	6424811

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 85.7534 / max 619.1265, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178636	63.1397	1824
178635	20.4698	1806
178632	1.7352	1056
208664	0.3471	178
178634	0.0616	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.02	gold quality
ganglionic eminence	UBERON:0004023	98.69	gold quality
body of uterus	UBERON:0009853	98.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.56	gold quality
left ovary	UBERON:0002119	98.52	gold quality
right ovary	UBERON:0002118	98.51	gold quality
endocervix	UBERON:0000458	98.48	gold quality
cerebellar hemisphere	UBERON:0002245	98.47	gold quality
right testis	UBERON:0004534	98.46	gold quality
right uterine tube	UBERON:0001302	98.43	gold quality
cerebellar cortex	UBERON:0002129	98.41	gold quality
left testis	UBERON:0004533	98.40	gold quality
left uterine tube	UBERON:0001303	98.35	gold quality
ectocervix	UBERON:0012249	98.25	gold quality
cortical plate	UBERON:0005343	98.06	gold quality
mucosa of stomach	UBERON:0001199	97.89	gold quality
right lobe of thyroid gland	UBERON:0001119	97.88	gold quality
stromal cell of endometrium	CL:0002255	97.87	gold quality
right adrenal gland cortex	UBERON:0035827	97.85	gold quality
left adrenal gland	UBERON:0001234	97.80	gold quality
transverse colon	UBERON:0001157	97.78	gold quality
right adrenal gland	UBERON:0001233	97.78	gold quality
lower esophagus	UBERON:0013473	97.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.78	gold quality
left lobe of thyroid gland	UBERON:0001120	97.77	gold quality
left adrenal gland cortex	UBERON:0035825	97.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.74	gold quality
skin of abdomen	UBERON:0001416	97.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.57

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BRCA1
HNRNPD
NOS2
PTH
RPL3	Unknown

Upstream regulators (CollecTRI, top): BRCA1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• KSRP do indeed interact with the c-src transcript in vivo, and that these associations change with the differentiated state of the cell. (PMID:14657238)
• KSRP, a KH domain-containing ARE-BP, is an essential factor for ARE-directed mRNA decay. Some KH motifs of KSRP mediate RNA binding, mRNA decay, and interactions with the exosome. (PMID:15175153)
• IL-8 RNA from IL-1beta-stimulated cytoplasmic extract revealed a 20-fold greater association of transcript with the stabilizing factor HuR vs. the destabilizing factor KSRP in breast cancer cells (PMID:15514971)
• KHSRP, tethered to mRNAs, elicits mRNA decay. (PMID:16648466)
• These results indicate that KSRP functions as a limiting factor in inflammatory gene expression. (PMID:17908789)
• These data indicate a novel role for KSRP in parathyroid hormone gene expression. (PMID:18583400)
• The over-expression of a novel protein family, far upstream binding proteins (FUBPs) was identified in both stages of hepatocellular carcinoma and confirmed by western blots. (PMID:19003864)
• The authors report that phosphorylation leads to the unfolding of the structurally atypical and unstable KH1, creating a site for 14-3-3zeta binding. (PMID:19198587)
• KSRP serves as a component of both Drosha and Dicer complexes and regulates the biogenesis of a subset of miRNAs (PMID:19458619)
• The coordinated activation of FBP-1 and FBP-2 represents a novel and frequent pro-tumorigenic mechanism promoting proliferation (tumor growth) and motility (dissemination) of human liver cancer cells. (PMID:19585652)
• Knock-down of either exosome components or KSRP by siRNAs prevents PMR1-mediated cleavage of PTH mRNA. (PMID:19775426)
• Dishevelled-KSRP complex operates in Wnt regulation of beta-catenin, functioning post-transcriptionally upon CTNNB1 mRNA stability. (PMID:20332102)
• hnRNP A1 and KSRP have antagonistic roles in the post-transcriptional regulation of let-7a expression. (PMID:20639884)
• In this review we will discuss in detail KSRP ability to i) promote decay of labile mRNAs interacting with some components of the mRNA decay machinery and ii) favor the maturation of a select group of microRNA precursors[review] (PMID:21196264)
• KSRP binds to the terminal loop sequence of a subset of miRNA precursors promoting their maturation (REVIEW) (PMID:21627028)
• KHSRP was identified as being involved in the regulation of rpL3 gene expression via alternative pre-mRNA splicing. (PMID:21705779)
• KSRP-dependent silencing was reversed by IL-1, a strong inducer of IL-6 mRNA and protein expression. (PMID:21795706)
• RACK1 binds to KH-type splicing regulatory protein (KSRP), a member of the Dicer complex, and is required for the recruitment of mature miRNAs to the RNA-induced silencing complex (RISC). (PMID:21935400)
• The role of KSRP in mRNA decay and microRNA precursor maturation. (PMID:21935887)
• Binding of the human KSRP protein to let-7 miRNA precursors positively regulates their processing to mature let-7, thereby contributing to control of cell proliferation, apoptosis and differentiation (PMID:23142982)
• Enterovirus 71 infection cleaved FBP2, which altered its function when its carboxyl terminus was cleaved. (PMID:23345520)
• KSRP induces enhanced processing of pri- and pre-miR-155 in cystic fibrosis lung epithelial cells. (PMID:23524258)
• subcellular localization of KSRP is regulated by competing interactions with DDX1 or 14-3-3 (PMID:24023901)
• The ability of KSRP to integrate different levels of gene expression is required for proper immune response. [Review] (PMID:24845017)
• Functional analysis of selected regulated proteins revealed that knockdown of HNRPD, PHB2 and UB2V2 can increase HCMV replication, while knockdown of A4 and KSRP resulted in decreased HCMV replication. (PMID:25910425)
• Khsrp as a highly regulated RBP in response to genotoxic stress. (PMID:25993413)
• The expression of KSRP in liver epithelial cells controlled by mir-27b. (PMID:26631623)
• High FBP2 expression is associated with doxorubicin resistance in breast cancer . (PMID:26810065)
• TGF-beta-induced KHSRP silencing is central in a pathway leading to gene-expression. (PMID:27396342)
• The miRNA biogenesis factors, DDX17 and KHSRP, regulate the protein level of Ago2 in human cells. (PMID:27478153)
• Results show that KHSRP protein is highly expressed in osteosarcoma cells and provide evidence for its important roles in regulatory controls of osteosarcoma pathogenesis. (PMID:27573585)
• Further analyses indicated that KHSRP was involved in miR-26a maturation and inhibited the expression of PTEN in small cell lung cancer cells (PMID:27644194)
• The interaction between the KLHL12 and the C-terminal domain of KHSRP contributed to KHSRP ubiquitination, leading to downregulation of enterovirus internal ribosome entry sites-mediated translation in infected cells. (PMID:27899653)
• The authors find that KHSRP associates with the regulatory domain of RIG-I to maintain the receptor in an inactive state and attenuate its sensing of viral RNA (vRNA). (PMID:28248290)
• mechanistic evidence that KSRP promotes the down-regulation of Spry4 by a previously unidentified mechanism, i.e. post-transcriptional mRNA regulation. (PMID:28275056)
• KSRP decreased EGR3 mRNA stability in an ARE-independent manner. (PMID:28847731)
• we discovered a novel mechanism underlying SUMOylation of KHSRP regulating the production of some special miRNAs. (PMID:29020972)
• KSRP, miR-129, and RUNX1 participate in a regulatory axis to control the outcome of myeloid differentiation. (PMID:29127290)
• Decreased expression of KHSRP, thus increasing CDKN1a (p21) expression. (PMID:29735546)
• The KH-type splicing regulatory protein (KSRP) regulates type III interferon expression post-transcriptionally. (PMID:30578289)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	khsrp	ENSDARG00000026489
mus_musculus	Khsrp	ENSMUSG00000007670
rattus_norvegicus	Khsrp	ENSRNOG00000047628
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00010908
caenorhabditis_elegans		WBGENE00013347
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

Far upstream element-binding protein 2 — Q92945 (reviewed: Q92945)

Alternative names: KH type-splicing regulatory protein, p75

All UniProt accessions (9): Q92945, M0QXW7, M0QYG1, M0QYH3, M0R0C6, M0R0I5, M0R251, M0R263, M0R3J3

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the dendritic targeting element and may play a role in mRNA trafficking. Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3’-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.

Subunit / interactions. Part of a ternary complex containing FUBP2, PTBP1, PTBP2 and HNRPH1. Interacts with PARN. Interacts with PQBP1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Detected in neural and non-neural cell lines.

Post-translational modifications. Phosphorylation at Ser-193 leads to the unfolding of the unstable KH domain 1, creating a site for 14-3-3 YWHAZ binding, which promotes nuclear localization and impairs the RNA degradation function.

Domain organisation. KH domains KH 3 and KH 4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of degradation.

Similarity. Belongs to the KHSRP family.

RefSeq proteins (3): NP_001353228, NP_001353229, NP_003676 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR015096	FUBP_C	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR047369	KH-I_FUBP2_rpt2	Domain
IPR047370	KH-I_FUBP2_rpt3	Domain
IPR047371	KH-I_FUBP2_rpt4	Domain
IPR047372	KH-I_FUBP2_rpt1	Domain

Pfam: PF00013, PF09005

UniProt features (88 total): strand 18, modified residue 17, helix 12, compositionally biased region 9, turn 9, sequence conflict 6, region of interest 5, domain 4, repeat 4, cross-link 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2HH2	SOLUTION NMR
2HH3	SOLUTION NMR
2JVZ	SOLUTION NMR
2OPU	SOLUTION NMR
2OPV	SOLUTION NMR
4B8T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92945-F1	63.13	0.20

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 (19): 2, 40, 87, 99, 100, 125, 129, 131, 181, 184, 193, 274, 411, 413, 415, 442, 480, 121, 121

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA

MSigDB gene sets: 333 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MORF_DNMT1, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, MORF_ESPL1, MORF_BUB1, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MORF_RRM1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_HDAC2, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_LOW_DENSITY_LIPOPROTEIN_PARTICLE_CLEARANCE

GO Biological Process (16): RNA splicing, via transesterification reactions (GO:0000375), regulation of transcription by RNA polymerase II (GO:0006357), mRNA processing (GO:0006397), RNA splicing (GO:0008380), miRNA metabolic process (GO:0010586), negative regulation of low-density lipoprotein particle clearance (GO:0010989), regulation of mRNA stability (GO:0043488), negative regulation of nitric oxide biosynthetic process (GO:0045019), mRNA transport (GO:0051028), positive regulation of mRNA catabolic process (GO:0061014), 3’-UTR-mediated mRNA destabilization (GO:0061158), cellular response to cytokine stimulus (GO:0071345), regulation of DNA-templated transcription (GO:0006355), mRNA catabolic process (GO:0006402), protein folding (GO:0006457), regulation of miRNA metabolic process (GO:2000628)

GO Molecular Function (7): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR AU-rich region binding (GO:0035925), protein folding chaperone (GO:0044183), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), exosome (RNase complex) (GO:0000178), cytoplasmic stress granule (GO:0010494)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
PERK regulates gene expression	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA processing	2
mRNA metabolic process	2
regulation of mRNA catabolic process	2
nucleic acid binding	2
binding	2
intracellular anatomical structure	2
RNA splicing	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
RNA metabolic process	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
regulation of RNA stability	1
nitric oxide biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
RNA transport	1
mRNA catabolic process	1
positive regulation of catabolic process	1
positive regulation of mRNA metabolic process	1
mRNA destabilization	1
response to cytokine	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
RNA catabolic process	1
negative regulation of gene expression	1
cellular process	1
protein maturation	1
miRNA metabolic process	1
regulation of RNA metabolic process	1
RNA binding	1
mRNA 3’-UTR binding	1
molecular_function	1
protein folding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

2448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KHSRP	DROSHA	Q9NRR4	969
KHSRP	DICER1	Q9UPY3	959
KHSRP	PARN	O95453	927
KHSRP	HNRNPD	P07029	904
KHSRP	HNRNPF	P52597	871
KHSRP	HNRNPH1	P31943	842
KHSRP	ELAVL1	Q15717	826
KHSRP	PTBP2	Q9UKA9	811
KHSRP	HNRNPR	O43390	803
KHSRP	HNRNPA1	P09651	794
KHSRP	ZFP36	P26651	793
KHSRP	FBP1	P09467	779
KHSRP	LIN28A	Q9H9Z2	725
KHSRP	CELF1	Q92879	725
KHSRP	ELAVL4	P26378	698

IntAct

185 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
KHSRP	Ywhaz	psi-mi:“MI:0407”(direct interaction)	0.590
KHSRP	Ywhaz	psi-mi:“MI:0915”(physical association)	0.590
KHSRP	Hnrnpa1	psi-mi:“MI:0914”(association)	0.480
KHSRP	Hnrnpa1	psi-mi:“MI:0915”(physical association)	0.480
KHSRP	Hnrnpd	psi-mi:“MI:0915”(physical association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
KMT2B	MEN1	psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
KHSRP	AKT1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	KHSRP	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP14	KHSRP	psi-mi:“MI:0915”(physical association)	0.400
DICER1	KHSRP	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (391): KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-MS), KHSRP (Affinity Capture-Western), CHCHD2 (Co-fractionation), CPSF6 (Co-fractionation), CPSF7 (Co-fractionation), FUBP3 (Co-fractionation), HTRA2 (Co-fractionation)

ESM2 similar proteins: A0A1W2P872, A1L1C7, A4IIM2, B2RYD2, F1LQ48, O57406, O88532, O95319, P14866, P28659, P51513, P57723, P57724, Q28HE9, Q2PFW9, Q32PX7, Q3U0V1, Q3US41, Q4QQT3, Q4R535, Q58A45, Q5F3T7, Q5NVC8, Q5R8Y8, Q5R995, Q5U231, Q640Q5, Q6DGV1, Q6GPM1, Q6NXG1, Q6P0B1, Q6PF35, Q792H5, Q7T2T1, Q7TSY6, Q7ZXE2, Q80WA4, Q8R081, Q8UVD9, Q91WJ8

Diamond homologs: A6ZKR5, B3LNH0, C7GND0, C8Z3W4, O19048, O74919, O75179, O88477, P38199, P57721, P57722, P57723, P57724, P60335, Q08CK7, Q0VCU0, Q15365, Q15366, Q3U0V1, Q5E9A3, Q61990, Q8IWZ3, Q8UVD9, Q92945, Q99NH0, Q99PF5, Q9NZI8, Q9VCA8, Q8CGX0, A0A0B4KGY6, F4KDN0, O19049, P61978, P61979, P61980, Q32PX7, Q3T0D0, Q4R4M6, Q5R5H8, Q86XN8

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
PCSK7	down-regulates	KHSRP	phosphorylation
14-3-3	down-regulates	KHSRP	binding
AKT	“down-regulates activity”	KHSRP	phosphorylation
ATM	up-regulates	KHSRP	phosphorylation
KHSRP	down-regulates	DVL3	binding
AKT1	“down-regulates activity”	KHSRP	phosphorylation
PTBP2	“up-regulates activity”	KHSRP	binding
MAPK14	“down-regulates activity”	KHSRP	phosphorylation
KHSRP	“down-regulates quantity by destabilization”	CDKN1A	“post transcriptional regulation”
AKT2	down-regulates	KHSRP	phosphorylation
KHSRP	“up-regulates quantity by expression”	SRC	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 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
Insulin receptor signalling cascade	5	25.2×	1e-04
FCERI mediated MAPK activation	7	18.2×	2e-05
MicroRNA (miRNA) biogenesis	5	17.2×	4e-04
FLT3 Signaling	5	13.0×	1e-03
NCAM signaling for neurite out-growth	6	12.3×	4e-04
Signaling by FGFR2 in disease	6	12.0×	4e-04
mRNA 3’-end processing	8	11.8×	5e-05
Signaling by FGFR1 in disease	5	11.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
pre-miRNA processing	5	35.3×	6e-05
RNA catabolic process	5	14.3×	3e-03
negative regulation of Notch signaling pathway	5	13.6×	4e-03
intrinsic apoptotic signaling pathway	6	13.5×	7e-04
autophagosome maturation	5	11.0×	7e-03
negative regulation of translation	8	9.9×	3e-04
autophagosome assembly	6	8.5×	7e-03
insulin receptor signaling pathway	6	8.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	111
Likely benign	5
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685192	GRCh37/hg19 9p24.3-q34.3(chr9:203861-141020388)x3	Pathogenic

SpliceAI

2561 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6415297:TTGCG:T	acceptor_gain	1.0000
19:6415298:TGCG:T	acceptor_gain	1.0000
19:6415299:GCG:G	acceptor_gain	1.0000
19:6415300:CG:C	acceptor_gain	1.0000
19:6415300:CGC:C	acceptor_gain	1.0000
19:6415301:GCTG:G	acceptor_loss	1.0000
19:6415302:C:CC	acceptor_gain	1.0000
19:6415302:C:CG	acceptor_loss	1.0000
19:6415303:T:C	acceptor_loss	1.0000
19:6415304:G:C	acceptor_gain	1.0000
19:6415375:CTCA:C	donor_loss	1.0000
19:6415376:TCA:T	donor_loss	1.0000
19:6415377:CACC:C	donor_loss	1.0000
19:6415378:A:AC	donor_gain	1.0000
19:6415378:A:AT	donor_loss	1.0000
19:6415378:AC:A	donor_gain	1.0000
19:6415379:C:CC	donor_gain	1.0000
19:6415379:CC:C	donor_gain	1.0000
19:6415379:CCTTG:C	donor_gain	1.0000
19:6415455:GGCC:G	acceptor_loss	1.0000
19:6415456:GCC:G	acceptor_loss	1.0000
19:6415458:C:CA	acceptor_loss	1.0000
19:6415458:C:CC	acceptor_gain	1.0000
19:6415459:T:G	acceptor_loss	1.0000
19:6415533:CCGAT:C	donor_gain	1.0000
19:6415735:C:CC	acceptor_gain	1.0000
19:6415806:A:AC	donor_gain	1.0000
19:6415807:C:CC	donor_gain	1.0000
19:6415897:C:CC	acceptor_gain	1.0000
19:6416290:ATACT:A	donor_loss	1.0000

AlphaMissense

4823 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6415224:A:C	Y682D	1.000
19:6415226:T:C	Y681C	1.000
19:6415227:A:C	Y681D	1.000
19:6415227:A:G	Y681H	1.000
19:6415234:C:A	W678C	1.000
19:6415234:C:G	W678C	1.000
19:6415236:A:G	W678R	1.000
19:6415236:A:T	W678R	1.000
19:6415402:C:A	W648C	1.000
19:6415402:C:G	W648C	1.000
19:6415404:A:G	W648R	1.000
19:6415404:A:T	W648R	1.000
19:6415556:C:A	W622C	1.000
19:6415556:C:G	W622C	1.000
19:6415558:A:G	W622R	1.000
19:6415558:A:T	W622R	1.000
19:6415694:C:A	W576C	1.000
19:6415694:C:G	W576C	1.000
19:6415696:A:G	W576R	1.000
19:6415696:A:T	W576R	1.000
19:6416506:A:T	I491N	1.000
19:6416509:A:G	L490P	1.000
19:6416518:G:T	A487D	1.000
19:6416519:C:G	A487P	1.000
19:6416542:C:A	G479V	1.000
19:6416542:C:T	G479D	1.000
19:6416543:C:G	G479R	1.000
19:6416545:C:G	R478P	1.000
19:6416548:A:T	I477N	1.000
19:6416553:G:C	F475L	1.000

dbSNP variants (sampled 300 via entrez): RS1000118096 (19:6420961 C>T), RS1000193563 (19:6421197 T>C,G), RS1000362447 (19:6425573 C>A,G), RS1000496135 (19:6422245 G>A,C), RS1000640156 (19:6412692 A>C), RS1000800364 (19:6425743 C>A,T), RS1000914019 (19:6414296 C>A,G,T), RS1001086313 (19:6416792 C>T), RS1001110991 (19:6425729 C>A,T), RS1001167481 (19:6419702 G>A), RS1001167780 (19:6424065 G>A,T), RS1001395268 (19:6424798 C>T), RS1001574119 (19:6415719 G>A), RS1001626403 (19:6415903 G>A,C), RS1001641539 (19:6419869 C>A,T)

Disease associations

OMIM: gene MIM:603445 | disease phenotypes: MIM:619864

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy, childhood-onset, remitting	Moderate	Autosomal dominant

Mondo (2): leukodystrophy, childhood-onset, remitting (MONDO:0859246), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000522_1	Height	3.000000e-06
GCST003873_1	Colorectal cancer (alcohol consumption interaction)	2.000000e-08
GCST003873_2	Colorectal cancer (alcohol consumption interaction)	1.000000e-07
GCST009178_7	Caudal middle frontal gyrus volume	1.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795105 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.00	Kd	1001	nM	CHEMBL3752910
5.99	ED50	1026	nM	CHEMBL3752910
5.41	Kd	3928	nM	CHEMBL5653589
5.39	ED50	4027	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 26 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	2148621: Binding affinity to human KHSRP incubated for 45 mins by Kinobead based pull down assay	kd	1.0005	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148621: Binding affinity to human KHSRP incubated for 45 mins by Kinobead based pull down assay	kd	3.9285	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression, increases expression, decreases response to substance, affects expression	4
methylmercuric chloride	affects cotreatment, increases expression	3
sodium arsenite	increases abundance, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic	increases methylation, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Caffeine	affects phosphorylation, increases expression	2
Dronabinol	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
decabromobiphenyl ether	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	increases phosphorylation	1
artenimol	affects binding	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
nutlin 3	increases secretion, affects cotreatment	1
2-amino-14,16-dimethyloctadecan-3-ol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1

ChEMBL screening assays

25 unique, capped per target: 25 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1798291	Binding	Binding affinity to KSRP/FUBP2 in human HCT116 cell lysate at 2 uM after 9 hrs by SDS-PAGE analysis	KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4YU	SUi003-A	Induced pluripotent stem cell	Male
CVCL_A4YV	SUi003-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice