DDX54

Summary

DDX54 (DEAD-box helicase 54, HGNC:20084) is a protein-coding gene on chromosome 12q24.13, encoding ATP-dependent RNA helicase DDX54 (Q8TDD1). Nucleolar RNA helicase that is involved in diverse cellular processes including ribosome biogenesis, DNA damage response, RNA splicing, transcriptional regulation, innate immunity, and nervous system development. It is a common-essential gene (DepMap: required in 99.8% 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 nucleolar protein encoded by this gene interacts in a hormone-dependent manner with nuclear receptors, and represses their transcriptional activity. Alternative splice variants that encode different isoforms have been found for this gene.

Source: NCBI Gene 79039 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 228 total — 3 likely-pathogenic
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_024072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20084
Approved symbol	DDX54
Name	DEAD-box helicase 54
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC2835, APR-5, DP97
Ensembl gene	ENSG00000123064
Ensembl biotype	protein_coding
OMIM	611665
Entrez	79039

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 23 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000306014, ENST00000314045, ENST00000546869, ENST00000546898, ENST00000548786, ENST00000549271, ENST00000550016, ENST00000551344, ENST00000551912, ENST00000552375, ENST00000865163, ENST00000865164, ENST00000865165, ENST00000865166, ENST00000865167, ENST00000865168, ENST00000865169, ENST00000937022, ENST00000937023, ENST00000937024, ENST00000937025, ENST00000937026, ENST00000937027, ENST00000937028, ENST00000937029, ENST00000949502, ENST00000949503, ENST00000949504, ENST00000949505

RefSeq mRNA: 2 — MANE Select: NM_024072 NM_001111322, NM_024072

CCDS: CCDS31907, CCDS44984

Canonical transcript exons

ENST00000306014 — 20 exons

Exon	Start	End
ENSE00000755453	113161893	113161997
ENSE00000917991	113161270	113161382
ENSE00000938024	113172353	113172563
ENSE00000938025	113169770	113169904
ENSE00001132666	113165644	113165717
ENSE00001132668	113165802	113166032
ENSE00001252046	113162932	113163045
ENSE00001252141	113174640	113174771
ENSE00001252151	113174875	113174936
ENSE00002371784	113157173	113159109
ENSE00003462217	113164067	113164285
ENSE00003464883	113176840	113176935
ENSE00003527979	113179935	113180005
ENSE00003536032	113177052	113177093
ENSE00003603279	113178977	113179026
ENSE00003642137	113180929	113181058
ENSE00003673664	113163132	113163274
ENSE00003674448	113179143	113179331
ENSE00003790737	113175036	113175157
ENSE00003903521	113185278	113185478

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.6780 / max 389.5991, expressed in 1815 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133352	33.7158	1811
206904	0.5965	261
133349	0.1604	74
133351	0.1280	49
133350	0.0773	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.35	gold quality
nucleus accumbens	UBERON:0001882	95.94	gold quality
upper arm skin	UBERON:0004263	95.89	silver quality
putamen	UBERON:0001874	95.39	gold quality
tendon of biceps brachii	UBERON:0008188	95.28	gold quality
kidney epithelium	UBERON:0004819	95.20	gold quality
left ventricle myocardium	UBERON:0006566	95.06	gold quality
nasal cavity epithelium	UBERON:0005384	94.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.59	gold quality
caudate nucleus	UBERON:0001873	94.49	gold quality
gastrocnemius	UBERON:0001388	94.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.25	silver quality
mucosa of transverse colon	UBERON:0004991	93.71	gold quality
vena cava	UBERON:0004087	93.63	gold quality
muscle of leg	UBERON:0001383	93.55	gold quality
lower esophagus mucosa	UBERON:0035834	93.49	gold quality
body of pancreas	UBERON:0001150	93.31	gold quality
right uterine tube	UBERON:0001302	93.26	gold quality
prefrontal cortex	UBERON:0000451	93.06	gold quality
myocardium	UBERON:0002349	92.96	silver quality
granulocyte	CL:0000094	92.94	gold quality
parotid gland	UBERON:0001831	92.90	gold quality
skin of leg	UBERON:0001511	92.77	gold quality
skeletal muscle organ	UBERON:0014892	92.70	gold quality
skin of abdomen	UBERON:0001416	92.58	gold quality
ventricular zone	UBERON:0003053	92.49	gold quality
right lobe of thyroid gland	UBERON:0001119	92.48	gold quality
body of stomach	UBERON:0001161	92.34	gold quality
right ovary	UBERON:0002118	92.27	gold quality
caecum	UBERON:0001153	92.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting DDX54, 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-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-593-3P	99.22	67.28	1327

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• Identifies DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 (locus 79039) as a novel nucleolar protein in HeLa cells. (PMID:11790298)
• Identifies DEAD box polypeptide 54 (similar to RIKEN cDNA 2410015A15 gene) as one of 213 different nucleolar proteins in HeLa cells. (PMID:12429849)
• Kinetic analysis of DEAD box helicases, including DEAD box polypeptide 54, in response to transcription inhibition. (PMID:15635413)
• Identifies dead box polypeptide 54 as a 14-3-3-binding protein. (PMID:16260042)
• Includes the identification of DEAD box polypeptide 54 phosphopeptides following the stimulation of HeLa cells with epidermal growth factor. (PMID:17081983)
• DP97 was found to be a gene (or promoter)-selective co-activator for hCAR (PMID:22910411)
• Ddx54 plays an important role in central nervous system myelination, presumably in myelin sheath formation after the differentiation of oligodendrocytes. (PMID:23239230)
• Missense mutation in DDX54 gene is associated with neurodevelopmental disorder. (PMID:31256877)
• SNHG10/DDX54/PBX3 Feedback Loop Contributes to Gastric Cancer Cell Growth. (PMID:32712782)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx54	ENSDARG00000105286
mus_musculus	Ddx54	ENSMUSG00000029599
rattus_norvegicus	Iqcd	ENSRNOG00000001377
drosophila_melanogaster	CG32344	FBGN0052344
caenorhabditis_elegans		WBGENE00022378

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), 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), DDX23 (ENSG00000174243), DDX10 (ENSG00000178105), DDX28 (ENSG00000182810), DDX41 (ENSG00000183258), DDX53 (ENSG00000184735), DDX51 (ENSG00000185163), DDX42 (ENSG00000198231), DDX39B (ENSG00000198563), DDX47 (ENSG00000213782), DDX3X (ENSG00000215301), DDX52 (ENSG00000278053)

Protein

Protein identifiers

ATP-dependent RNA helicase DDX54 — Q8TDD1 (reviewed: Q8TDD1)

Alternative names: ATP-dependent RNA helicase DP97, DEAD box RNA helicase 97 kDa, DEAD box protein 54

All UniProt accessions (4): Q8TDD1, F8VRX4, H0YHH7, H0YHZ9

UniProt curated annotations — full annotation on UniProt →

Function. Nucleolar RNA helicase that is involved in diverse cellular processes including ribosome biogenesis, DNA damage response, RNA splicing, transcriptional regulation, innate immunity, and nervous system development. Plays an essential role in the formation of the ribosome active site by remodeling rRNA structure and initiating peptidyl transferase center formation. Represses the transcriptional activity of several nuclear receptors. Regulates transcriptome dynamics during DNA damage response. Mechanistically, acts via increased interaction with a well-defined class of pre-mRNAs that contain introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex. These activities lead to reduced intron retention and enhanced processing rates of its target transcripts. Acts as an inhibitor of type I interferon antiviral response by facilitating ALKBH5-mediated demethylation of specific transcripts. Contributes to central nervous system myelination, likely through regulation of oligodendrocyte differentiation and myelin sheath formation.

Subunit / interactions. Interacts in a hormone-dependent manner with nuclear receptors. Interacts with core spliceosomal and spliceosome-associated proteins.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Expressed in the fallopian tube, cervix and uterus. Also expressed in the brain.

Similarity. Belongs to the DEAD box helicase family. DDX54/DBP10 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDD1-1	1	yes
Q8TDD1-2	2

RefSeq proteins (2): NP_001104792, NP_076977* (*=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
IPR012541	DBP10_C	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014014	RNA_helicase_DEAD_Q_motif	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR033517	DDX54/DBP10_DEAD-box_helicase	Domain
IPR050079	DEAD_box_RNA_helicase	Family

Pfam: PF00270, PF00271, PF08147

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (41 total): compositionally biased region 9, modified residue 9, sequence variant 9, region of interest 4, mutagenesis site 3, domain 2, short sequence motif 2, chain 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FKW	ELECTRON MICROSCOPY	2.5
8FKX	ELECTRON MICROSCOPY	2.59
8FKY	ELECTRON MICROSCOPY	2.67
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDD1-F1	70.89	0.27

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): 140–147

Post-translational modifications (9): 34, 39, 41, 75, 644, 696, 698, 782, 788

Mutagenesis-validated functional residues (3):

Position	Phenotype
250	loss of atpase activity.
280	no change in ifn-beta promoter down-regulation activity.
401	no change in ifn-beta promoter down- regulation activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_RIBOSOME_BIOGENESIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PID_ERB_GENOMIC_PATHWAY, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, AGGAGTG_MIR483, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (5): rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA metabolic process (GO:0016070), estrogen receptor signaling pathway (GO:0030520), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (11): transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), RNA helicase activity (GO:0003724), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nuclear estrogen receptor binding (GO:0030331), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), helicase activity (GO:0004386), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cellular anatomical structure	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid metabolic process	1
nuclear receptor-mediated steroid hormone signaling pathway	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nuclear receptor binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

3765 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX54	DHX8	Q14562	777
DDX54	DHX57	Q6P158	662
DDX54	ATRAID	Q6UW56	573
DDX54	MAGEH1	Q9H213	544
DDX54	ESR2	Q92731	532
DDX54	DHX58	Q96C10	519
DDX54	DHX30	Q7L2E3	508
DDX54	DHX34	Q14147	500
DDX54	DHX37	Q8IY37	490
DDX54	DHX16	O60231	480
DDX54	DDX46	Q7L014	476
DDX54	TUFM	P49411	464
DDX54	DHX15	O43143	459
DDX54	RBM28	Q9NW13	456
DDX54	DICER1	Q9UPY3	452

IntAct

220 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CSNK2B	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
MECP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
WDR48	USP12	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
ESR1		psi-mi:“MI:0914”(association)	0.460
PTPRD	DDX54	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410

BioGRID (462): DDX54 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), DDX54 (Co-fractionation), DDX54 (Co-fractionation), DDX54 (Co-fractionation), DDX54 (Co-fractionation), DDX54 (Co-fractionation), SSB (Co-fractionation), DDX54 (Affinity Capture-RNA), DDX54 (Reconstituted Complex)

ESM2 similar proteins: A1A4H6, A1C7F7, A1CHL3, A1CNV8, A1D1R8, A1DHV3, A2QAX7, A3LSN3, A4QYM6, A5D7C1, A5DKW3, A5DLR3, A5E3K3, A7A0P8, A7TJM9, P0C2N8, P0CQ92, P0CQ93, P26802, P32892, P93008, Q07886, Q09903, Q0INC5, Q0UMB9, Q0UWC8, Q0V1Z7, Q1E2B2, Q2HEB0, Q2UFL0, Q2UQI6, Q4I830, Q4WRV2, Q4X0C2, Q5RC67, Q6C7X8, Q6CEB8, Q6CJV1, Q6FNA2, Q6FW42

Diamond homologs: A0R8U6, A1CNV8, A1CR32, A1CTZ6, A1D1R8, A1D405, A1DNG2, A2QAX7, A2QRY2, A2RB17, A2YV85, A3BT52, A3LS22, A3LSN3, A3LZT3, A4QYM6, A4R5B8, A5DKW3, A5DLR3, A5DQF1, A5DY34, A5DZT7, A6QRQ7, A6QUM7, A6RUH2, A6RW56, A6ZXU0, A7A0P8, A7EML8, A7ESL7, A7F4L5, A7TGW7, A7TJM9, B9XXL6, O25029, O49289, P0C2N7, P0C2N8, P0CR00, P0CR01

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 226 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	13	10.4×	4e-08
Viral mRNA Translation	13	10.4×	4e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	10.3×	4e-08
SRP-dependent cotranslational protein targeting to membrane	16	10.1×	1e-09
Formation of a pool of free 40S subunits	14	9.9×	3e-08
Selenocysteine synthesis	13	9.9×	4e-08
Eukaryotic Translation Termination	13	9.9×	4e-08
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	9.7×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription by RNA polymerase I	5	15.7×	1e-03
liver regeneration	6	14.9×	4e-04
cytoplasmic translation	16	14.4×	2e-11
peptidyl-tyrosine phosphorylation	7	14.3×	1e-04
positive regulation of viral genome replication	5	14.1×	2e-03
ribosomal large subunit biogenesis	6	12.9×	9e-04
negative regulation of translation	12	11.4×	2e-07
rRNA processing	16	11.0×	8e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	174
Likely benign	14
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
691936	NM_024072.4(DDX54):c.647A>G (p.Asn216Ser)	Likely pathogenic
691937	NM_024072.4(DDX54):c.58T>A (p.Trp20Arg)	Likely pathogenic
691938	NM_024072.4(DDX54):c.1832G>A (p.Arg611Gln)	Likely pathogenic

SpliceAI

2918 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113161264:TCTCA:T	donor_loss	1.0000
12:113161266:TCA:T	donor_loss	1.0000
12:113161268:ACCT:A	donor_loss	1.0000
12:113161269:C:A	donor_loss	1.0000
12:113161892:CAGGT:C	donor_gain	1.0000
12:113161995:TCCCT:T	acceptor_loss	1.0000
12:113161998:C:CC	acceptor_gain	1.0000
12:113162931:CCA:C	donor_gain	1.0000
12:113163041:TCAGG:T	acceptor_gain	1.0000
12:113163042:CAGG:C	acceptor_gain	1.0000
12:113163042:CAGGC:C	acceptor_gain	1.0000
12:113163043:AGG:A	acceptor_gain	1.0000
12:113163044:GG:G	acceptor_gain	1.0000
12:113163045:GC:G	acceptor_loss	1.0000
12:113163046:C:CC	acceptor_gain	1.0000
12:113163046:C:T	acceptor_loss	1.0000
12:113163049:C:CT	acceptor_gain	1.0000
12:113163050:A:T	acceptor_gain	1.0000
12:113163059:G:C	acceptor_gain	1.0000
12:113163059:G:GC	acceptor_gain	1.0000
12:113163128:TCA:T	donor_loss	1.0000
12:113163129:CA:C	donor_loss	1.0000
12:113163130:A:AC	donor_gain	1.0000
12:113163130:A:T	donor_loss	1.0000
12:113163130:AC:A	donor_gain	1.0000
12:113163130:ACC:A	donor_gain	1.0000
12:113163130:ACCC:A	donor_gain	1.0000
12:113163130:ACCCC:A	donor_gain	1.0000
12:113163131:C:CC	donor_gain	1.0000
12:113163131:C:G	donor_loss	1.0000

AlphaMissense

5678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:113172362:G:C	H424D	0.999
12:113175074:G:T	A279D	0.999
12:113176844:C:G	D250H	0.999
12:113179174:A:G	L178P	0.999
12:113179273:C:T	G145D	0.999
12:113179279:C:T	G143D	0.999
12:113161997:C:A	W732C	0.998
12:113161997:C:G	W732C	0.998
12:113172362:G:T	H424N	0.998
12:113172431:C:G	G401R	0.998
12:113172436:G:T	A399D	0.998
12:113172502:C:G	R377P	0.998
12:113174676:A:C	F344L	0.998
12:113174676:A:T	F344L	0.998
12:113174678:A:G	F344L	0.998
12:113175077:G:A	S278F	0.998
12:113176843:T:A	D250V	0.998
12:113176843:T:G	D250A	0.998
12:113176847:C:G	A249P	0.998
12:113176849:T:A	E248V	0.998
12:113176915:C:G	R226P	0.998
12:113177078:A:C	F210L	0.998
12:113177078:A:T	F210L	0.998
12:113177080:A:G	F210L	0.998
12:113179260:G:C	C149W	0.998
12:113179264:G:T	A148D	0.998
12:113179269:C:A	K146N	0.998
12:113179269:C:G	K146N	0.998
12:113179270:T:A	K146M	0.998
12:113179271:T:G	K146Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000023461 (12:113180314 C>A,T), RS1000047048 (12:113164346 C>T), RS1000295980 (12:113185426 G>A,C), RS1000337415 (12:113169032 C>T), RS1000421181 (12:113158056 C>G), RS1000473493 (12:113168833 G>C), RS1000669216 (12:113175950 C>A), RS1000706553 (12:113174395 G>A), RS1000948981 (12:113182501 T>G), RS1001029772 (12:113178986 C>A), RS1001081962 (12:113178487 A>G), RS1001208950 (12:113176318 A>C,G), RS1001314438 (12:113184926 T>C), RS1001346527 (12:113185157 C>T), RS1001502366 (12:113184639 A>T)

Disease associations

OMIM: gene MIM:611665 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (3): intellectual disability (MONDO:0001071), renal hypoplasia (MONDO:0019637), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Renal hypoplasia (Orphanet:93101), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000089	Renal hypoplasia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001738_6	Response to fenofibrate (adiponectin levels)	5.000000e-08
GCST005951_2	Body mass index	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

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
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
propylparaben	increases expression	1
deoxynivalenol	increases expression	1
lead acetate	increases expression	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
nivalenol	increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
avobenzone	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Lead	decreases expression	1
Ozone	affects expression, increases abundance	1

Clinical trials (associated diseases)

390 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,
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
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
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
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
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
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
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)
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