DHX29

Summary

DHX29 (DExH-box helicase 29, HGNC:15815) is a protein-coding gene on chromosome 5q11.2, encoding ATP-dependent RNA helicase DHX29 (Q7Z478). ATP-binding RNA helicase involved in translation initiation. It is a selective cancer dependency (DepMap: 15.0% of cell lines).

This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein functions in translation initiation, and is specifically required for ribosomal scanning across stable mRNA secondary structures during initiation codon selection. This protein may also play a role in sensing virally derived cytosolic nucleic acids. Knockdown of this gene results in reduced protein translation and impaired proliferation of cancer cells.

Source: NCBI Gene 54505 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 2 (q < 0.05)
• Cancer dependency (DepMap): dependent in 15.0% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.58 (moderately constrained)
• MANE Select transcript: NM_019030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15815
Approved symbol	DHX29
Name	DExH-box helicase 29
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000067248
Ensembl biotype	protein_coding
OMIM	612720
Entrez	54505

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 20 protein_coding, 8 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000251636

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 2

ENST00000251636, ENST00000504778, ENST00000508346, ENST00000513447, ENST00000867272, ENST00000867273, ENST00000867274, ENST00000867275, ENST00000867276, ENST00000912930, ENST00000912931, ENST00000962095, ENST00000962096, ENST00000982551, ENST00000982552, ENST00001047272, ENST00001047273, ENST00001047274, ENST00001047275, ENST00001047276, ENST00001047277, ENST00001072241, ENST00001094602, ENST00001110721, ENST00001110722, ENST00001110723, ENST00001110724, ENST00001129516, ENST00001129517, ENST00001134589

RefSeq mRNA: 3 — MANE Select: NM_019030 NM_001345964, NM_001345965, NM_019030

CCDS: CCDS34158

Canonical transcript exons

ENST00000251636 — 27 exons

Exon	Start	End
ENSE00001261045	55283203	55283811
ENSE00002039745	55256055	55256540
ENSE00002068150	55307387	55307694
ENSE00003476212	55262630	55262932
ENSE00003484416	55270578	55270706
ENSE00003485512	55269413	55269637
ENSE00003504392	55294017	55294145
ENSE00003508753	55297285	55297398
ENSE00003510610	55274866	55275010
ENSE00003520336	55274614	55274731
ENSE00003523618	55272087	55272175
ENSE00003524168	55277106	55277282
ENSE00003524374	55290218	55290344
ENSE00003531826	55298591	55298664
ENSE00003556319	55261368	55261499
ENSE00003585303	55270412	55270487
ENSE00003598324	55281372	55281515
ENSE00003600743	55285696	55285861
ENSE00003602793	55295379	55295524
ENSE00003607780	55289270	55289428
ENSE00003619880	55259848	55259944
ENSE00003633316	55273293	55273377
ENSE00003634001	55267138	55267231
ENSE00003639425	55267686	55267822
ENSE00003640177	55296220	55296349
ENSE00003681956	55285293	55285416
ENSE00003684841	55276266	55276406

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 94.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8998 / max 207.6385, expressed in 1800 samples.

Highest expression (Bgee): esophagus squamous epithelium, palpebral conjunctiva, secondary oocyte, visceral pleura, seminal vesicle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DHX29 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.7e-36	+1.77	5:55307710:C:T
Esophagus Mucosa	eqtl	1.7e-04	+0.11	5:55243085:G:A
Artery Aorta	eqtl	4.6e-03	+0.19	5:55450837:T:C
Brain Nucleus accumbens basal ganglia	eqtl	8.1e-03	-0.74	5:55803041:T:C
Prostate	eqtl	1.6e-02	+0.17	5:55497796:A:G
Lung	eqtl	2.2e-02	+0.17	5:55556351:A:C
Brain Frontal Cortex BA9	eqtl	2.5e-02	+0.20	5:55814520:A:ACG
Muscle Skeletal	eqtl	3.3e-02	-0.18	5:55582565:T:C
Stomach	sqtl	3.6e-02	-1.06	5:55760184:ATGT:A
Esophagus Muscularis	eqtl	3.7e-02	-0.08	5:55307994:T:C
Colon Sigmoid	eqtl	4.1e-02	+0.48	5:55179333:C:A
Adipose Subcutaneous	sqtl	4.2e-02	-1.17	5:55883896:A:G
Artery Tibial	eqtl	4.7e-02	+0.10	5:55253002:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
61692	17.8998	1800

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	94.42	gold quality
palpebral conjunctiva	UBERON:0001812	94.30	gold quality
secondary oocyte	CL:0000655	94.06	gold quality
visceral pleura	UBERON:0002401	93.15	gold quality
seminal vesicle	UBERON:0000998	92.98	gold quality
parietal pleura	UBERON:0002400	92.84	gold quality
tibia	UBERON:0000979	92.69	gold quality
germinal epithelium of ovary	UBERON:0001304	92.59	gold quality
biceps brachii	UBERON:0001507	92.58	gold quality
gingiva	UBERON:0001828	92.58	gold quality
eye	UBERON:0000970	92.49	gold quality
pleura	UBERON:0000977	92.40	gold quality
gingival epithelium	UBERON:0001949	92.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.90	gold quality
calcaneal tendon	UBERON:0003701	91.35	gold quality
epithelium of esophagus	UBERON:0001976	91.10	gold quality
amniotic fluid	UBERON:0000173	90.95	gold quality
epithelium of nasopharynx	UBERON:0001951	90.62	gold quality
trabecular bone tissue	UBERON:0002483	90.47	gold quality
oral cavity	UBERON:0000167	90.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.38	gold quality
sperm	CL:0000019	90.29	gold quality
squamous epithelium	UBERON:0006914	90.26	gold quality
cortical plate	UBERON:0005343	89.84	gold quality
nephron tubule	UBERON:0001231	89.78	gold quality
mammalian vulva	UBERON:0000997	89.42	gold quality
gastrocnemius	UBERON:0001388	89.24	gold quality
blood vessel layer	UBERON:0004797	89.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.11	gold quality
jejunal mucosa	UBERON:0000399	89.10	gold quality
skin of hip	UBERON:0001554	89.10	gold quality
penis	UBERON:0000989	89.09	gold quality
jejunum	UBERON:0002115	89.02	gold quality
deltoid	UBERON:0001476	88.78	gold quality
islet of Langerhans	UBERON:0000006	88.73	gold quality
muscle of leg	UBERON:0001383	88.73	gold quality
epithelium of mammary gland	UBERON:0003244	88.71	gold quality
synovial joint	UBERON:0002217	88.67	gold quality
mammary duct	UBERON:0001765	88.62	gold quality
saphenous vein	UBERON:0007318	88.55	gold quality
corpus epididymis	UBERON:0004359	88.53	gold quality
cauda epididymis	UBERON:0004360	88.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.46	gold quality
thoracic mammary gland	UBERON:0005200	88.44	gold quality
skeletal muscle organ	UBERON:0014892	88.43	gold quality
muscle organ	UBERON:0001630	88.42	gold quality
choroid plexus epithelium	UBERON:0003911	88.39	gold quality
mammary gland	UBERON:0001911	88.36	gold quality
colonic mucosa	UBERON:0000317	88.33	gold quality
renal medulla	UBERON:0000362	88.01	gold quality
endometrium	UBERON:0001295	87.89	gold quality
urethra	UBERON:0000057	87.82	gold quality
upper leg skin	UBERON:0004262	87.80	gold quality
renal glomerulus	UBERON:0000074	87.65	gold quality
lower lobe of lung	UBERON:0008949	87.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.62	gold quality
oviduct epithelium	UBERON:0004804	87.54	gold quality
vastus lateralis	UBERON:0001379	87.51	gold quality
skeletal muscle tissue	UBERON:0001134	87.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.46	gold quality
pericardium	UBERON:0002407	87.41	gold quality
adrenal tissue	UBERON:0018303	87.27	gold quality
placenta	UBERON:0001987	87.26	gold quality
ventricular zone	UBERON:0003053	87.25	gold quality
superior surface of tongue	UBERON:0007371	87.24	gold quality
quadriceps femoris	UBERON:0001377	87.19	gold quality
kidney epithelium	UBERON:0004819	87.16	gold quality
pigmented layer of retina	UBERON:0001782	87.07	gold quality
metanephric glomerulus	UBERON:0004736	87.06	gold quality
retina	UBERON:0000966	87.05	gold quality
tendon	UBERON:0000043	86.93	gold quality
metanephros	UBERON:0000081	86.93	gold quality
oocyte	CL:0000023	86.92	gold quality
male germ cell	CL:0000015	86.83	gold quality
body of tongue	UBERON:0011876	86.76	gold quality
bronchial epithelial cell	CL:0002328	86.73	gold quality
popliteal artery	UBERON:0002250	86.69	gold quality
tibial artery	UBERON:0007610	86.69	gold quality
tongue	UBERON:0001723	86.65	gold quality
tongue squamous epithelium	UBERON:0006919	86.54	gold quality
urinary bladder	UBERON:0001255	86.46	gold quality
monocyte	CL:0000576	86.42	gold quality
tibialis anterior	UBERON:0001385	86.40	gold quality
muscle tissue	UBERON:0002385	86.40	gold quality
cartilage tissue	UBERON:0002418	86.38	gold quality
mononuclear cell	CL:0000842	86.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.32	gold quality
parotid gland	UBERON:0001831	86.28	gold quality
uterus	UBERON:0000995	86.26	gold quality
tonsil	UBERON:0002372	86.17	gold quality
pharyngeal mucosa	UBERON:0000355	86.09	gold quality
ganglionic eminence	UBERON:0004023	86.04	gold quality
aorta	UBERON:0000947	86.02	gold quality
stromal cell of endometrium	CL:0002255	86.01	gold quality
myometrium	UBERON:0001296	86.00	gold quality
caput epididymis	UBERON:0004358	85.96	gold quality
leukocyte	CL:0000738	85.94	gold quality
heart right ventricle	UBERON:0002080	85.90	gold quality
hair follicle	UBERON:0002073	85.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	366.57
E-MTAB-5061	no	4.04
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	17.6	high
Corpus callosum	tissue	17.5
Spinal cord	tissue	16.5
Kidney	tissue	15.8	high
Choroid plexus	tissue	15.7
Midbrain	tissue	15.7
Putamen	tissue	15.4
Hippocampal formation	tissue	14.6
Thyroid gland	tissue	14.4	high
Thalamus	tissue	14.3
Skeletal muscle	tissue	14.2	medium
Medulla oblongata	tissue	14.2
Cerebellum	tissue	14.1	high
Superior colliculi	tissue	13.9
Pons	tissue	13.8
Tongue	tissue	13.8
Nucleus accumbens	tissue	13.7
Substantia nigra	tissue	13.7
Septum	tissue	13.7
Ventral forebrain	tissue	13.6
Periaqueductal gray	tissue	13.3
Cerebral cortex	tissue	13.0	high
Olfactory bulb	tissue	13.0
Somatosensory cortex	tissue	13.0
Motor cortex	tissue	12.9
Prostate	tissue	12.6	high
Entorhinal cortex	tissue	12.6
Retrosplenial and cingulate cortex	tissue	12.5
Basal ganglia	tissue	12.4	high
Hypothalamus	tissue	12.3
Liver	tissue	12.3	medium
Caudate putamen	tissue	12.3
Occipital cortex	tissue	12.3
Prefrontal cortex	tissue	12.0
Retrosplenial cortex	tissue	12.0
Esophagus	tissue	11.9	high
Amygdala	tissue	11.9
Temporal cortex	tissue	11.9
Cervix	tissue	11.8	high
Smooth muscle	tissue	11.7	medium
Postcentral gyrus	tissue	11.7
Locus coeruleus	tissue	11.5
Breast	tissue	11.3	high
Seminal vesicle	tissue	11.3	high
Urinary bladder	tissue	11.2	high
Insular cortex	tissue	11.1
Pancreas	tissue	11.0	high
Hippocampus	tissue	10.8	high
Placenta	tissue	10.7	high
Heart muscle	tissue	10.0	high
Pituitary gland	tissue	9.8
Endometrium 1	tissue	9.8	high
Vagina	tissue	9.6	high
Frontal cortex	tissue	9.6
Salivary gland	tissue	9.5	high
Thymus	tissue	9.3
Rectum	tissue	9.2	high
Appendix	tissue	9.2	high
Skin 1	tissue	9.1	high
Adipose tissue	tissue	9.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (20.4), Vermis (19.5), Flocculonodular lobe (18.0), White matter (17.5), Dorsal spinal cord (16.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DHX29 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

19 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-943	97.81	64.42	694
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-591	96.29	68.16	611
HSA-MIR-624-5P	96.00	68.88	728

Functional genomics

gnomAD constraint: pLI 0.000279, LOEUF 0.578, missense Z 2.15 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000251636 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:55,256,491–55,285,321	882 / 1082.4	0.81	no
5:55,285,322–55,285,844	60 / 94.2	0.64	no
5:55,285,845–55,307,573	405 / 416.8	0.97	no
DepMap (CRISPR cell-line fitness): dependent in 15.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): U-2946 (-1.422), G415 (-1.378), DAN-G (-1.35), MOLM-14 (-1.342), JVE-207 (-1.301), SU-DHL-10 (-1.268), HB11;19 (-1.266), MC116 (-1.225), UPCI-SCC-200 (-1.167), MM127 (-1.098), LoVo (-1.085), 950-5-BIK (-1.062), KP-N-SI9s (-1.057), BICR 31 (-1.018), HCC2429 (-1.015).

Literature-anchored findings (GeneRIF, showing 9)

• Study reports that these 7 eIFs are not sufficient for efficient 48S complex formation on mRNAs with highly structured 5’UTRs, and that this process requires the DExH-box protein DHX29. (PMID:19109895)
• Down-regulation of DHX29 leads to impaired translation, resulting in disassembly of polysomes and accumulation of mRNA-free 80S monomers. DHX29 depletion also impedes cancer cell growth in culture and in xenografts. (PMID:20018725)
• Roles of individual domains in the function of DHX29, an essential factor required for translation of structured mammalian mRNAs. (PMID:23047696)
• Helicase proteins DHX29 and RIG-I cosense cytosolic nucleic acids in the human airway system. (PMID:24821782)
• DHX29 is another example of an initiation factor contributing to start codon selection. (PMID:27067542)
• DHX29 and eIF3 cooperate in scanning on structured mRNAs. Our findings support previous genetic data on the role of eIF3 during scanning (PMID:27733651)
• A critical role for DHX29 in innate immune response; molecular insights into the mechanisms by which DHX29 recognizes 5’ structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity. (PMID:29462185)
• 5q11.2 deletion syndrome revisited-Further narrowing of the smallest region of overlap for the main clinical characteristics of the syndrome. (PMID:34322994)
• Functional role and ribosomal position of the unique N-terminal region of DHX29, a factor required for initiation on structured mammalian mRNAs. (PMID:34883515)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx29	ENSDARG00000040326
mus_musculus	Dhx29	ENSMUSG00000042426
rattus_norvegicus	Dhx29	ENSRNOG00000010369

Paralogs (18): DHX33 (ENSG00000005100), YTHDC2 (ENSG00000047188), DHX8 (ENSG00000067596), DHX32 (ENSG00000089876), DHX35 (ENSG00000101452), DHX40 (ENSG00000108406), DHX15 (ENSG00000109606), HELB (ENSG00000127311), DHX30 (ENSG00000132153), DHX34 (ENSG00000134815), DHX9 (ENSG00000135829), DHX38 (ENSG00000140829), DQX1 (ENSG00000144045), DHX37 (ENSG00000150990), TDRD9 (ENSG00000156414), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2145374) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal embryo size	1
abnormal embryo turning	1
abnormal neural tube closure	1
embryonic growth retardation	1
impaired glucose tolerance	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAZ4	100.0%	Diamond
Pan troglodytes	Q7YR39	99.6%	Diamond
Bos taurus	Q2NKY8	97.9%	Diamond
Sus scrofa	Q767K6	96.5%	Diamond
Drosophila persimilis	B4GEU5	95.0%	Diamond
Drosophila pseudoobscura pseudoobscura	Q296Q5	95.0%	Diamond
Arabidopsis thaliana	F4KGU4	94.7%	Diamond
Drosophila sechellia	B4HLH4	92.5%	Diamond
Drosophila melanogaster	Q9VF26	92.5%	Diamond
Drosophila erecta	B3P3W1	89.5%	Diamond
Drosophila yakuba	B4PRJ9	89.5%	Diamond
Drosophila mojavensis	B4K5R2	83.1%	Diamond
Xenopus laevis	Q68FK8	81.3%	Diamond
Drosophila grimshawi	B4JT42	79.1%	Diamond
Gallus gallus	Q5ZI74	76.2%	Diamond
Culex quinquefasciatus	B0XDC4	74.6%	Diamond
Aedes aegypti	Q16JS8	74.6%	Diamond
Saccharomyces cerevisiae S288C	P53131	72.3%	Diamond
Escherichia coli K-12	P43329	70.0%	Diamond
Drosophila ananassae	B3M383	69.7%	Diamond
Caenorhabditis elegans	P34498	67.3%	Diamond
Dictyostelium discoideum	Q54NJ4	65.9%	Diamond
Drosophila willistoni	B4NBB0	65.5%	Diamond
Anopheles gambiae	Q7QCW2	53.2%	Diamond
Oryza sativa Japonica Group	Q1EHT7	49.9%	Diamond
Schizosaccharomyces pombe 972h-	Q03319	47.2%	Diamond
Mycosarcoma maydis	P0C7L7	38.6%	Diamond
Trypanosoma brucei brucei TREU927	Q581T1	36.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CCNO-DT	ncRNA	121009647
MTREX-AS1	ncRNA	124900979
MTREX	protein-coding	23517
MIR449C	ncRNA	100313923
MCIDAS-AS1	ncRNA	124900978
CDC20B	protein-coding	166979
MCIDAS	protein-coding	345643
CCNO	protein-coding	10309
MIR449B	ncRNA	693123
MIR5687	ncRNA	100847019
PLPP1	protein-coding	8611

Protein

Protein identifiers

ATP-dependent RNA helicase DHX29 — Q7Z478 (reviewed: Q7Z478)

Alternative names: DEAH box protein 29, Nucleic acid helicase DDXx

All UniProt accessions (2): Q7Z478, H0Y8L1

UniProt curated annotations — full annotation on UniProt →

Function. ATP-binding RNA helicase involved in translation initiation. Part of the 43S pre-initiation complex that is required for efficient initiation on mRNAs of higher eukaryotes with structured 5’-UTRs by promoting efficient NTPase-dependent 48S complex formation. Specifically binds to the 40S ribosome near the mRNA entrance. Does not possess a processive helicase activity.

Subunit / interactions. Part of the 43S pre-initiation complex (PIC) that contains at least Met-tRNA, EIF1, EIF1A (EIF1AX or EIF1AY), EIF2S1, EIF2S2, EIF2S3, EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L, EIF3M, DHX29 and the 40S ribosomal subunit.

Subcellular location. Cytoplasm.

Similarity. Belongs to the DEAD box helicase family. DEAH subfamily.

RefSeq proteins (3): NP_001332893, NP_001332894, NP_061903* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR007502	Helicase-assoc_dom	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR011709	DEAD-box_helicase_OB_fold	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR034730	DHX29	Family
IPR048333	HA2_WH	Domain
IPR056328	DSRM_DHX29	Domain
IPR056890	UBA_DHX29-like	Domain
IPR059023	RNA_hel_CTD	Domain

Pfam: PF00270, PF00271, PF04408, PF07717, PF21010, PF24385, PF24899, PF26026

Catalyzed reactions (Rhea)

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

UniProt features (22 total): sequence conflict 4, modified residue 3, region of interest 3, coiled-coil region 3, domain 2, compositionally biased region 2, sequence variant 2, chain 1, binding site 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
22TU	Human 80S ribosome in complex with DHX29	ELECTRON MICROSCOPY	3
9CPA	Structure of a Mammalian DHX29-bound 43S Pre-initiation Complex	ELECTRON MICROSCOPY	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z478-F1	74.75	0.28

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
595–602	ATP

Post-translational modifications (3)

Type	Positions
Phosphoserine	71, 192, 200

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 139 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, ELVIDGE_HYPOXIA_DN, GOBP_RIBOSOME_BIOGENESIS, GOBP_TRANSLATIONAL_INITIATION, GOBP_RIBOSOME_ASSEMBLY, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, GOBP_FORMATION_OF_TRANSLATION_PREINITIATION_COMPLEX, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (6): formation of translation preinitiation complex (GO:0001731), ribosome assembly (GO:0042255), positive regulation of translational initiation (GO:0045948), translation (GO:0006412), translational initiation (GO:0006413), positive regulation of translation (GO:0045727)

GO Molecular Function (14): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), translation initiation factor activity (GO:0003743), helicase activity (GO:0004386), ATP binding (GO:0005524), translation activator activity (GO:0008494), ATP hydrolysis activity (GO:0016887), ribonucleoside triphosphate phosphatase activity (GO:0017111), ribosomal small subunit binding (GO:0043024), cadherin binding (GO:0045296), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), hydrolase activity (GO:0016787), hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides (GO:0016818)

GO Cellular Component (3): eukaryotic 43S preinitiation complex (GO:0016282), cytosolic small ribosomal subunit (GO:0022627), cytoplasm (GO:0005737)

GO top-level categories

46 GO namespaces:

Category	Terms
translational initiation	3
positive regulation of translation	2
translation	2
ATP-dependent activity	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
ribosome biogenesis	1
membraneless organelle assembly	1
regulation of translational initiation	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
metabolic process	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
translation factor activity	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
translation regulator activity	1
ribonucleoside triphosphate phosphatase activity	1
pyrophosphatase activity	1
ribosome binding	1
cell adhesion molecule binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on acid anhydrides	1
cytosolic small ribosomal subunit	1
cytosolic translation preinitiation complex	1
small ribosomal subunit	1
cytosolic ribosome	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
formation of translation preinitiation complex	BP	mutant phenotype
ribosome assembly	BP	mutant phenotype
cytosolic small ribosomal subunit	CC	direct assay
eukaryotic 43S preinitiation complex	CC	direct assay
RNA binding	MF	high-throughput assay
cadherin binding	MF	high-throughput assay
ribonucleoside triphosphate phosphatase activity	MF	mutant phenotype
ribosomal small subunit binding	MF	direct assay
translation activator activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,538 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX29	EIF1	P41567	918
DHX29	EIF4A2	Q14240	880
DHX29	EIF4A1	P04765	878
DHX29	EIF1AX	P47813	838
DHX29	EIF4B	P23588	824
DHX29	EIF4G1	Q04637	799
DHX29	EIF5	P55010	671
DHX29	DDX1	Q92499	644
DHX29	DDX3X	O00571	631
DHX29	EIF5B	O60841	620
DHX29	DDX24	Q9GZR7	590
DHX29	DDX60	Q8IY21	576
DHX29	DDX21	Q9NR30	546
DHX29	EIF3J	O75822	534
DHX29	EIF4E	P06730	529

IntAct

Human interaction partners of DHX29 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
RPS9	physical association	0.400	1
CENPT	physical association	0.000	1
PISD	physical association	0.000	1
TBC1D17	physical association	0.000	1

BioGRID (130 interactions; top human partners by supporting records): CDX1 (Affinity Capture-MS; 2 records), LRRC59 (Proximity Label-MS; 2 records), MYC (Affinity Capture-MS; 2 records), NPM1 (Affinity Capture-MS; 2 records), OTUD6B (Affinity Capture-MS; 2 records), RECQL5 (Co-fractionation; 2 records), RPS9 (Cross-Linking-MS (XL-MS); 2 records), STAU1 (Proximity Label-MS; 2 records), ADAM17 (Affinity Capture-MS), APEX1 (Affinity Capture-RNA), BAG2 (Affinity Capture-MS), BIRC3 (Affinity Capture-MS), BMI1 (Affinity Capture-MS), CALD1 (Cross-Linking-MS (XL-MS)), CAPRIN1 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for DHX29: 37 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 2,060):

Position(s)	Effect	Δscore	Sites
5:55267136–55267137	donor_loss	1.0000	5
5:55267823	acceptor_loss	1.0000	2
5:55267828	acceptor_gain	1.0000
5:55267836	acceptor_gain	1.0000
5:55269411–55269412	donor_loss	1.0000	5
5:55269638–55269639	acceptor_loss	1.0000	5
5:55270399	donor_gain	1.0000
5:55270576–55270577	donor_loss	1.0000	5
5:55272085–55272086	donor_loss	1.0000	4
5:55272090	donor_gain	1.0000

AlphaMissense

2,997 missense substitutions predicted likely pathogenic (of 8,998 scored), across 778 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M733	9	0.950	0.998
D702	8	0.999	1.000
D712	8	0.997	0.999
D947	8	0.995	0.999
D385	8	0.994	0.999
F916	8	0.994	1.000
H705	8	0.992	0.997
F873	8	0.991	0.999
H904	8	0.989	0.998
D1134	8	0.980	0.995
H438	8	0.965	0.997
S734	8	0.956	0.999
S602	8	0.954	1.000
D941	8	0.950	0.991
F382	8	0.949	0.997
F746	8	0.941	0.993
F136	8	0.938	0.993
F1111	8	0.938	0.994
F175	8	0.931	0.994
D160	8	0.925	0.977

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.95e-06
Kidney Chromophobe (TCGA)	unfavorable	0.000197
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000384

Disease associations

OMIM: gene MIM:612720 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST008399_7	Cocaine dependence	8e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105909 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 12 human assays (13 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4092701	IC50	58000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, increases activity	4
bisphenol A	decreases expression, affects cotreatment, decreases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
1,6-hexamethylene diisocyanate	affects expression	1
trimellitic anhydride	affects expression	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
ammonium hexachloroplatinate	affects expression	1
zinc chromate	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Thiram	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4007299	Binding	Inhibition of full length recombinant human N-terminal FLAG-His-tagged DHX29 RNA dependent ATPase activity expressed in baculovirus infected Sf9 insect cells using single stranded poly(U) RNA as substrate after 30 mins by ADP-Glo luminescen	Discovery of selective ATP-competitive eIF4A3 inhibitors. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DHX29 across ~30M SureChEMBL compounds — explore on Sugi Predict.