DDX23

Summary

DDX23 (DEAD-box helicase 23, HGNC:17347) is a protein-coding gene on chromosome 12q13.12, encoding Probable ATP-dependent RNA helicase DDX23 (Q9BUQ8). Involved in pre-mRNA splicing and its phosphorylated form (by SRPK2) is required for spliceosomal B complex formation. It is a common-essential gene (DepMap: required in 98.3% of cancer cell lines).

This gene encodes a member of the DEAD box protein family. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a component of the U5 snRNP complex; it may facilitate conformational changes in the spliceosome during nuclear pre-mRNA splicing. An alternatively spliced transcript variant has been found for this gene, but its biological validity has not been determined.

Source: NCBI Gene 9416 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 145 total — 2 pathogenic, 3 likely-pathogenic
• Cancer dependency (DepMap): dependent in 98.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_004818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17347
Approved symbol	DDX23
Name	DEAD-box helicase 23
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	Prp28, U5-100KD, PRPF28, SNRNP100
Ensembl gene	ENSG00000174243
Ensembl biotype	protein_coding
OMIM	612172
Entrez	9416

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 9 protein_coding, 9 retained_intron, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000308025, ENST00000547135, ENST00000547165, ENST00000547290, ENST00000547842, ENST00000549795, ENST00000550834, ENST00000551098, ENST00000551189, ENST00000551331, ENST00000551468, ENST00000552069, ENST00000552369, ENST00000552512, ENST00000552555, ENST00000552802, ENST00000553065, ENST00000553182, ENST00000703178, ENST00000703179, ENST00000703180, ENST00000703181, ENST00000703182, ENST00000870156, ENST00000926596, ENST00000926597, ENST00000926598

RefSeq mRNA: 1 — MANE Select: NM_004818 NM_004818

CCDS: CCDS8770

Canonical transcript exons

ENST00000308025 — 17 exons

Exon	Start	End
ENSE00001261899	48831142	48831316
ENSE00001261958	48837281	48837393
ENSE00001261968	48837524	48837657
ENSE00001299878	48852084	48852163
ENSE00001306086	48829756	48830692
ENSE00003462559	48833277	48833519
ENSE00003541528	48839844	48839909
ENSE00003558829	48843940	48844050
ENSE00003560866	48845574	48845782
ENSE00003607338	48837942	48838080
ENSE00003609364	48834320	48834497
ENSE00003628624	48832422	48832573
ENSE00003660111	48836569	48836794
ENSE00003671305	48832078	48832186
ENSE00003676919	48836121	48836266
ENSE00003687722	48836894	48837037
ENSE00003790173	48840013	48840106

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.2260 / max 685.6169, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130743	24.3671	1810
130744	13.8589	1785

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.82	gold quality
sural nerve	UBERON:0015488	97.56	gold quality
granulocyte	CL:0000094	96.73	gold quality
ventricular zone	UBERON:0003053	96.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.99	gold quality
right uterine tube	UBERON:0001302	95.70	gold quality
body of stomach	UBERON:0001161	95.58	gold quality
ganglionic eminence	UBERON:0004023	95.54	gold quality
rectum	UBERON:0001052	95.51	gold quality
right lobe of thyroid gland	UBERON:0001119	95.51	gold quality
transverse colon	UBERON:0001157	95.47	gold quality
right ovary	UBERON:0002118	95.46	gold quality
left ovary	UBERON:0002119	95.42	gold quality
minor salivary gland	UBERON:0001830	95.38	gold quality
islet of Langerhans	UBERON:0000006	95.35	gold quality
mucosa of stomach	UBERON:0001199	95.29	gold quality
body of uterus	UBERON:0009853	95.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.16	gold quality
body of pancreas	UBERON:0001150	94.98	gold quality
left lobe of thyroid gland	UBERON:0001120	94.97	gold quality
metanephros cortex	UBERON:0010533	94.96	gold quality
skin of abdomen	UBERON:0001416	94.94	gold quality
left uterine tube	UBERON:0001303	94.93	gold quality
mucosa of transverse colon	UBERON:0004991	94.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.89	gold quality
lower esophagus	UBERON:0013473	94.88	gold quality
colonic epithelium	UBERON:0000397	94.86	gold quality
spleen	UBERON:0002106	94.85	gold quality
skin of leg	UBERON:0001511	94.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting DDX23, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-631	97.05	66.93	602

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• SRPK2 knock down results in hypophosphorylation of the arginine-serine (RS) domain-containing human PRP28 protein (PRP28, also known as DDX23), and destabilizes PRP28 association with the tri-snRNP. (PMID:18425142)
• These data provide new insights into the function of Prp28 in higher eukaryotes, and the requirements for stable tri-small nuclear ribonucleoproteins binding during B complex formation. (PMID:27377154)
• pausing of RNA polymerase II (RNA Pol II) initiates a signaling cascade whereby the serine/arginine protein kinase 2 (SRPK2) phosphorylates the DDX23 helicase, culminating in the suppression of R-loops. (PMID:28076779)
• new basis of DDX23-Linc00630-HDAC1 signal axis for understanding its pathogenicity, which could be further developed as a valuable therapeutic strategy (PMID:28473661)
• RNA Splicing by the Spliceosome. (PMID:31794245)
• Syndromic neurodevelopmental disorder associated with de novo variants in DDX23. (PMID:34050707)
• METTL3 enhances pancreatic ductal adenocarcinoma progression and gemcitabine resistance through modifying DDX23 mRNA N6 adenosine methylation. (PMID:36977668)
• SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23. (PMID:38743621)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx23	ENSDARG00000021945
mus_musculus	Ddx23	ENSMUSG00000003360
rattus_norvegicus	Ddx23	ENSRNOG00000060154
drosophila_melanogaster	CG10333	FBGN0032690
caenorhabditis_elegans		WBGENE00017162

Paralogs (38): DDX20 (ENSG00000064703), DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), DDX18 (ENSG00000088205), DDX24 (ENSG00000089737), DDX17 (ENSG00000100201), DDX49 (ENSG00000105671), DDX50 (ENSG00000107625), DDX5 (ENSG00000108654), DDX25 (ENSG00000109832), DDX6 (ENSG00000110367), DDX55 (ENSG00000111364), DDX59 (ENSG00000118197), DDX54 (ENSG00000123064), DDX39A (ENSG00000123136), DDX27 (ENSG00000124228), DDX31 (ENSG00000125485), DDX56 (ENSG00000136271), EIF4A3 (ENSG00000141543), DDX46 (ENSG00000145833), DDX4 (ENSG00000152670), EIF4A2 (ENSG00000156976), DDX19B (ENSG00000157349), EIF4A1 (ENSG00000161960), DDX21 (ENSG00000165732), DDX19A (ENSG00000168872), TDRD12 (ENSG00000173809), DDX10 (ENSG00000178105), DDX28 (ENSG00000182810), DDX41 (ENSG00000183258), DDX53 (ENSG00000184735), DDX51 (ENSG00000185163), DDX42 (ENSG00000198231), DDX39B (ENSG00000198563), DDX47 (ENSG00000213782), DDX3X (ENSG00000215301), DDX52 (ENSG00000278053)

Protein

Protein identifiers

Probable ATP-dependent RNA helicase DDX23 — Q9BUQ8 (reviewed: Q9BUQ8)

Alternative names: 100 kDa U5 snRNP-specific protein, DEAD box protein 23, PRP28 homolog, U5-100kD

All UniProt accessions (9): Q9BUQ8, A0A8V8TQ76, A0A8V8TQQ5, A0A8V8TR86, A0A8V8TRI2, F8VVA2, F8W1J5, H0YI52, H0YIL9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing and its phosphorylated form (by SRPK2) is required for spliceosomal B complex formation. Independently of its spliceosome formation function, required for the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA.

Subunit / interactions. The phosphorylated form (by SRPK2) is a component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Identified in the spliceosome C complex. Interacts with ERBB4. Interacts with ERCC6.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. In vitro phosphorylated by CLK1 and U1 snRNP-associated protein kinase. Phosphorylated by SRPK2 and this phosphorylation is required for its association with the tri-snRNP (U4/U6-U5 tri-small nuclear ribonucleoproteins) and subsequent spliceosomal B complex formation. May be phosphorylated by SRPK2 on Ser residues in the SR domain; the phosphorylation is required for the removal of inappropriate R-loops during transcription.

Similarity. Belongs to the DEAD box helicase family. DDX23/PRP28 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BUQ8-1	1	yes
Q9BUQ8-2	2

RefSeq proteins (1): NP_004809* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000629	RNA-helicase_DEAD-box_CS	Conserved_site
IPR001650	Helicase_C-like	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014014	RNA_helicase_DEAD_Q_motif	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR057479	PRP28/DDX23-like_helical	Domain

Pfam: PF00270, PF00271, PF25430

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (80 total): helix 37, strand 17, compositionally biased region 6, modified residue 4, sequence conflict 3, domain 2, cross-link 2, splice variant 2, turn 2, short sequence motif 2, chain 1, binding site 1, region of interest 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
4NHO	X-RAY DIFFRACTION	2
6QW6	ELECTRON MICROSCOPY	2.92
8Q91	ELECTRON MICROSCOPY	3.1
8QOZ	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8RC0	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
6QX9	ELECTRON MICROSCOPY	3.28
8Y6O	ELECTRON MICROSCOPY	3.38
8QP8	ELECTRON MICROSCOPY	3.5
8QPA	ELECTRON MICROSCOPY	3.7
8QPB	ELECTRON MICROSCOPY	3.7
8Q7W	ELECTRON MICROSCOPY	3.9
8QP9	ELECTRON MICROSCOPY	4.1
8QPK	ELECTRON MICROSCOPY	4.2
8R09	ELECTRON MICROSCOPY	4.3
8R0B	ELECTRON MICROSCOPY	4.4
8Q7X	ELECTRON MICROSCOPY	4.6
6AH0	ELECTRON MICROSCOPY	5.7
8R0A	ELECTRON MICROSCOPY	5.8
8R08	ELECTRON MICROSCOPY	6.1
8RM5	ELECTRON MICROSCOPY	6.9
3JCR	ELECTRON MICROSCOPY	7
8QXD	ELECTRON MICROSCOPY	9.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUQ8-F1	77.36	0.39

Functional residue map

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

Ligand- & substrate-binding residues (1): 435–442

Post-translational modifications (6): 14, 16, 107, 109, 686, 811

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 184 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, AACYNNNNTTCCS_UNKNOWN, MODULE_229, YY1_Q6, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, MODULE_98, AML1_01, GOBP_MRNA_CIS_SPLICING_VIA_SPLICEOSOME, RGAGGAARY_PU1_Q6

GO Biological Process (6): cis assembly of pre-catalytic spliceosome (GO:0000354), RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), R-loop processing (GO:0062176), mRNA processing (GO:0006397)

GO Molecular Function (10): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), mRNA binding (GO:0003729), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), nucleolus (GO:0005730), U4/U6 x U5 tri-snRNP complex (GO:0046540), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	2
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
ATP-dependent activity	2
binding	2
cellular anatomical structure	2
nuclear lumen	2
intracellular membraneless organelle	2
U5 snRNP	2
spliceosomal complex assembly	1
protein-RNA complex assembly	1
mRNA cis splicing, via spliceosome	1
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
chromatin remodeling	1
mRNA metabolic process	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
RNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
extracellular vesicle	1
Prp19 complex	1
spliceosomal complex	1
catalytic complex	1

Protein interactions and networks

STRING

3934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX23	DHX38	Q92620	966
DDX23	SRPK2	P78362	955
DDX23	SRPK1	Q96SB4	922
DDX23	PRPF6	O94906	904
DDX23	SNRNP200	O75643	903
DDX23	CD2BP2	O95400	891
DDX23	CLK1	P49759	830
DDX23	SNRPC	P09234	827
DDX23	EFTUD2	Q15029	775
DDX23	DHX15	O43143	768
DDX23	DHX16	O60231	744
DDX23	TXNL4A	P83876	735
DDX23	SART1	O43290	725
DDX23	PRPF31	Q8WWY3	709
DDX23	CWC25	Q9NXE8	707

IntAct

168 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
PRPF6	SART1	psi-mi:“MI:0914”(association)	0.750
DDX23	SNRNP40	psi-mi:“MI:0915”(physical association)	0.740
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730
SART1	PRPF3	psi-mi:“MI:0914”(association)	0.720
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
GCFC2	SNRNP200	psi-mi:“MI:0914”(association)	0.640
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRNP40	PRPF4	psi-mi:“MI:0914”(association)	0.640
DDX23	PRPF4	psi-mi:“MI:0914”(association)	0.640
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
PRP4K	PRPF4	psi-mi:“MI:0914”(association)	0.640
EFTUD2	SART1	psi-mi:“MI:0914”(association)	0.610
TOP1	HNRNPR	psi-mi:“MI:0914”(association)	0.600
DDX23	SF3A2	psi-mi:“MI:0915”(physical association)	0.560
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530

BioGRID (662): DDX23 (Affinity Capture-MS), DDX23 (Affinity Capture-MS), DDX23 (Affinity Capture-MS), DDX23 (Affinity Capture-MS), DDX23 (Affinity Capture-MS), PRPF3 (Affinity Capture-MS), IK (Affinity Capture-MS), SNRNP40 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), SNRNP200 (Affinity Capture-MS), PRPF8 (Affinity Capture-MS), TFIP11 (Affinity Capture-MS), EFTUD2 (Affinity Capture-MS), PAXBP1 (Affinity Capture-MS), AAR2 (Affinity Capture-MS)

ESM2 similar proteins: A1CHL3, A1CX72, A2QIL2, A4QYM6, A4RK80, A4RN46, A5DDF4, A5DKW3, A6RJA2, A6RW79, A7A0P8, A7EGG4, A7ENE0, O22907, P0CQ88, P0CQ89, P0CQ98, P0CQ99, P32892, P34498, P93008, Q09903, Q0CLX0, Q0D1K3, Q0UWC8, Q0V1Z7, Q1DMX8, Q1E2B2, Q2HAD8, Q2HEB0, Q2UH00, Q4I7F9, Q4IP34, Q4WPE9, Q53RK8, Q5BCU6, Q5RC67, Q6C024, Q6C7X8, Q6CDN5

Diamond homologs: A1CHL3, A1CQA9, A1CX72, A1D373, A2QIL2, A2QQA8, A3LNL1, A3LQW7, A4QSS5, A4RK80, A5DF03, A5DL80, A5DS77, A5DU73, A6RJA2, A6ZRX0, A7EGG4, G0SFM2, O22907, P0CQ88, P0CQ89, P0CQ98, P0CQ99, P23394, P24783, P46942, P93008, Q0CLX0, Q0D1K3, Q0DB53, Q0E3X4, Q0J7Y8, Q0UWC8, Q10MH8, Q1DMX8, Q2HEB0, Q2R1M8, Q2U070, Q2U2J6, Q2UH00

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DDX23	“form complex”	“U4/U6.U5 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 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
Metabolism of non-coding RNA	7	33.6×	5e-08
mRNA Splicing - Minor Pathway	14	23.8×	4e-14
mRNA Splicing	27	22.5×	2e-27
mRNA Splicing - Major Pathway	48	19.9×	8e-48
Processing of Capped Intron-Containing Pre-mRNA	30	18.7×	8e-28
mRNA Polyadenylation	23	15.3×	3e-19
RNA Polymerase II Transcription Termination	9	15.0×	5e-07
SARS-CoV-2 modulates host translation machinery	8	13.6×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	15	58.6×	2e-21
spliceosomal tri-snRNP complex assembly	7	51.1×	3e-09
RNA splicing, via transesterification reactions	11	44.6×	8e-14
spliceosomal snRNP assembly	11	41.5×	2e-13
negative regulation of mRNA splicing, via spliceosome	8	39.8×	2e-09
mRNA cis splicing, via spliceosome	6	38.6×	6e-07
U2-type prespliceosome assembly	9	36.5×	2e-10
regulation of mRNA splicing, via spliceosome	5	28.8×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	106
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1313838	NM_004818.3(DDX23):c.2127_2132del (p.Asn709_Leu710del)	Pathogenic
3069207	NM_004818.3(DDX23):c.1722C>A (p.Asn574Lys)	Pathogenic
1305256	NM_004818.3(DDX23):c.2131A>G (p.Lys711Glu)	Likely pathogenic
1699432	NM_004818.3(DDX23):c.1912C>T (p.Arg638Cys)	Likely pathogenic
2664152	NM_004818.3(DDX23):c.2437C>T (p.Arg813Cys)	Likely pathogenic

SpliceAI

2670 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48830688:GTAAT:G	acceptor_gain	1.0000
12:48830689:TAAT:T	acceptor_gain	1.0000
12:48830690:AAT:A	acceptor_gain	1.0000
12:48830691:AT:A	acceptor_gain	1.0000
12:48830692:TCT:T	acceptor_loss	1.0000
12:48830693:C:CC	acceptor_gain	1.0000
12:48830693:C:CG	acceptor_loss	1.0000
12:48830694:T:A	acceptor_loss	1.0000
12:48831137:CTTA:C	donor_loss	1.0000
12:48831138:TTA:T	donor_loss	1.0000
12:48831139:TA:T	donor_loss	1.0000
12:48831140:A:AC	donor_gain	1.0000
12:48831140:A:AG	donor_loss	1.0000
12:48831140:AC:A	donor_gain	1.0000
12:48831141:C:CC	donor_gain	1.0000
12:48831141:CC:C	donor_gain	1.0000
12:48831141:CCTT:C	donor_gain	1.0000
12:48831312:TTGTA:T	acceptor_gain	1.0000
12:48831313:TGTA:T	acceptor_gain	1.0000
12:48831314:GTA:G	acceptor_gain	1.0000
12:48831315:TA:T	acceptor_gain	1.0000
12:48831315:TACTG:T	acceptor_loss	1.0000
12:48831316:AC:A	acceptor_loss	1.0000
12:48831317:C:CC	acceptor_gain	1.0000
12:48831318:T:C	acceptor_loss	1.0000
12:48831320:T:TC	acceptor_gain	1.0000
12:48832062:C:CA	donor_gain	1.0000
12:48832063:C:A	donor_gain	1.0000
12:48832077:C:CA	donor_gain	1.0000
12:48832079:C:CA	donor_gain	1.0000

AlphaMissense

5380 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48830530:G:T	A801D	1.000
12:48830531:C:G	A801P	1.000
12:48830548:A:G	L795P	1.000
12:48830596:A:G	L779P	1.000
12:48830641:G:T	A764D	1.000
12:48830642:C:G	A764P	1.000
12:48830647:C:A	G762V	1.000
12:48830647:C:T	G762E	1.000
12:48830648:C:A	G762W	1.000
12:48830648:C:G	G762R	1.000
12:48830648:C:T	G762R	1.000
12:48830662:C:G	R757P	1.000
12:48830662:C:T	R757Q	1.000
12:48830663:G:C	R757G	1.000
12:48830665:C:A	G756V	1.000
12:48830665:C:T	G756E	1.000
12:48830666:C:G	G756R	1.000
12:48830666:C:T	G756R	1.000
12:48830671:C:A	R754L	1.000
12:48830671:C:G	R754P	1.000
12:48830671:C:T	R754H	1.000
12:48830672:G:A	R754C	1.000
12:48830672:G:C	R754G	1.000
12:48830672:G:T	R754S	1.000
12:48830674:C:A	G753V	1.000
12:48830674:C:T	G753D	1.000
12:48830675:C:A	G753C	1.000
12:48830675:C:G	G753R	1.000
12:48830680:C:G	R751P	1.000
12:48830681:G:C	R751G	1.000

dbSNP variants (sampled 300 via entrez): RS1000050240 (12:48847295 T>C), RS1000079795 (12:48849451 C>G), RS1000202162 (12:48834199 G>A), RS1000221416 (12:48847034 C>T), RS1000447660 (12:48852935 G>C), RS1000471860 (12:48841347 T>C), RS1000607374 (12:48848187 G>A), RS1000626166 (12:48841137 G>A), RS1000662593 (12:48848548 G>A,C), RS1000746746 (12:48846780 T>G), RS1000862354 (12:48853179 C>G,T), RS1001046932 (12:48835890 CA>C,CAA), RS1001150776 (12:48835534 C>A,T), RS1001367208 (12:48840396 C>A,T), RS1001389815 (12:48843847 G>A,T)

Disease associations

OMIM: gene MIM:612172 | disease phenotypes: MIM:618547

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	AD

Mondo (5): neurodevelopmental disorder (MONDO:0700092), bilateral perisylvian polymicrogyria (MONDO:0020340), neurodevelopmental disorder with visual defects and brain anomalies (MONDO:0032807), intellectual disability (MONDO:0001071), fetal growth restriction (MONDO:0005030)

Orphanet (2): Bilateral perisylvian polymicrogyria (Orphanet:98889), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001241_1	Bipolar disorder	1.000000e-06
GCST90000025_966	Appendicular lean mass	9.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
ICG 001	decreases expression	1
PP242	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, decreases expression	1

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