DHX40

Summary

DHX40 (DEAH-box helicase 40, HGNC:18018) is a protein-coding gene on chromosome 17q23.1, encoding Probable ATP-dependent RNA helicase DHX40 (Q8IX18). Probable ATP-dependent RNA helicase.

This gene encodes a member of the DExH/D box family of ATP-dependent RNA helicases that have an essential role in RNA metabolism. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 17.

Source: NCBI Gene 79665 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 88 total
• Druggable target: yes
• MANE Select transcript: NM_024612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18018
Approved symbol	DHX40
Name	DEAH-box helicase 40
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	ARG147, PAD, FLJ22060
Ensembl gene	ENSG00000108406
Ensembl biotype	protein_coding
OMIM	607570
Entrez	79665

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000251241, ENST00000425628, ENST00000538926, ENST00000577549, ENST00000577596, ENST00000578204, ENST00000580030, ENST00000580218, ENST00000583439, ENST00000584385, ENST00000867586, ENST00000930678, ENST00000930679, ENST00000930680, ENST00000930681, ENST00000961852, ENST00000961853, ENST00000961854, ENST00000961855, ENST00000961856, ENST00000961857

RefSeq mRNA: 2 — MANE Select: NM_024612 NM_001166301, NM_024612

CCDS: CCDS11617, CCDS54150

Canonical transcript exons

ENST00000251241 — 18 exons

Exon	Start	End
ENSE00000739767	59577266	59577365
ENSE00000739768	59579472	59579558
ENSE00001046361	59575340	59575471
ENSE00001112916	59605115	59605184
ENSE00001137652	59579697	59579879
ENSE00001137671	59574188	59574254
ENSE00001137708	59565610	59565783
ENSE00001207627	59599375	59599483
ENSE00001207633	59587896	59588053
ENSE00001207635	59586153	59586233
ENSE00002269560	59607033	59608345
ENSE00003475870	59602522	59602616
ENSE00003510661	59605446	59605674
ENSE00003515993	59570518	59570663
ENSE00003537704	59573740	59573967
ENSE00003593285	59598737	59598851
ENSE00003648416	59566627	59566794
ENSE00003669437	59573116	59573235

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.3232 / max 517.7107, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161960	48.6783	1817
161961	0.6448	357

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.46	gold quality
bronchial epithelial cell	CL:0002328	95.53	gold quality
ganglionic eminence	UBERON:0004023	94.80	gold quality
epithelium of bronchus	UBERON:0002031	94.71	gold quality
cartilage tissue	UBERON:0002418	94.68	gold quality
bronchus	UBERON:0002185	94.52	gold quality
calcaneal tendon	UBERON:0003701	94.31	gold quality
embryo	UBERON:0000922	93.88	gold quality
renal medulla	UBERON:0000362	93.79	gold quality
tendon	UBERON:0000043	93.57	gold quality
caput epididymis	UBERON:0004358	93.36	gold quality
islet of Langerhans	UBERON:0000006	93.29	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.28	gold quality
endometrium	UBERON:0001295	92.79	gold quality
tendon of biceps brachii	UBERON:0008188	92.76	gold quality
upper leg skin	UBERON:0004262	92.75	gold quality
urethra	UBERON:0000057	92.68	gold quality
skin of hip	UBERON:0001554	92.11	gold quality
corpus epididymis	UBERON:0004359	91.90	gold quality
sperm	CL:0000019	91.75	gold quality
germinal epithelium of ovary	UBERON:0001304	91.70	gold quality
secondary oocyte	CL:0000655	91.52	gold quality
synovial joint	UBERON:0002217	91.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.28	gold quality
epithelium of nasopharynx	UBERON:0001951	91.27	gold quality
penis	UBERON:0000989	91.25	gold quality
pericardium	UBERON:0002407	91.21	gold quality
saphenous vein	UBERON:0007318	91.03	gold quality
seminal vesicle	UBERON:0000998	91.00	gold quality
epithelium of mammary gland	UBERON:0003244	90.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting DHX40, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4719	99.73	72.10	3329

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx40	ENSDARG00000041586
mus_musculus	Dhx40	ENSMUSG00000018425
rattus_norvegicus	Dhx40	ENSRNOG00000004549

Paralogs (18): DHX33 (ENSG00000005100), YTHDC2 (ENSG00000047188), DHX29 (ENSG00000067248), DHX8 (ENSG00000067596), DHX32 (ENSG00000089876), DHX35 (ENSG00000101452), DHX15 (ENSG00000109606), HELB (ENSG00000127311), DHX30 (ENSG00000132153), DHX34 (ENSG00000134815), DHX9 (ENSG00000135829), DHX38 (ENSG00000140829), DQX1 (ENSG00000144045), DHX37 (ENSG00000150990), TDRD9 (ENSG00000156414), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

Probable ATP-dependent RNA helicase DHX40 — Q8IX18 (reviewed: Q8IX18)

Alternative names: DEAH box protein 40, Protein PAD

All UniProt accessions (6): Q8IX18, F5H625, J3KS08, J3KSW6, J3KSX9, J3KTK0

UniProt curated annotations — full annotation on UniProt →

Function. Probable ATP-dependent RNA helicase.

Tissue specificity. Ubiquitously expressed.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IX18-1	1	yes
Q8IX18-2	2
Q8IX18-3	3
Q8IX18-4	4

RefSeq proteins (2): NP_001159773, NP_078888* (*=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
IPR048333	HA2_WH	Domain

Pfam: PF00270, PF00271, PF04408, PF07717, PF21010

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (17 total): splice variant 5, sequence conflict 4, domain 2, region of interest 2, chain 1, short sequence motif 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IX18-F1	83.51	0.54

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): 76–83

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GCM_GSPT1, SOX9_B1, MODULE_239, MARTINEZ_RB1_TARGETS_DN, ROZANOV_MMP14_TARGETS_UP, GOBP_RNA_SPLICING, TGANTCA_AP1_C, CCCNNNNNNAAGWT_UNKNOWN, AACTTT_UNKNOWN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, CREB_Q3, YRTCANNRCGC_UNKNOWN, LEF1_Q6, GCM_NF2

GO Biological Process (1): mRNA splicing, via spliceosome (GO:0000398)

GO Molecular Function (10): RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), 3’-5’ RNA helicase activity (GO:0034458), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), RNA helicase activity (GO:0003724), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): spliceosomal complex (GO:0005681)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
RNA helicase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

2346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX40	PON2	Q15165	765
DHX40	PON1	P27169	650
DHX40	TCEAL4	Q96EI5	637
DHX40	YPEL2	Q96QA6	629
DHX40	PON3	Q15166	589
DHX40	NSRP1	Q9H0G5	576
DHX40	FBXO38	Q6PIJ6	529
DHX40	SLC35F4	A4IF30	508
DHX40	RALGAPB	Q86X10	488
DHX40	CHCT1	Q86WR6	474
DHX40	MAGED2	Q9UNF1	456
DHX40	DDX24	Q9GZR7	451
DHX40	FLVCR2	Q9UPI3	449
DHX40	DDX49	Q9Y6V7	444
DHX40	DDX55	Q8NHQ9	438

IntAct

52 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
USP7	BCOR	psi-mi:“MI:0914”(association)	0.660
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
DHX38	DHX16	psi-mi:“MI:0914”(association)	0.630
PSTPIP1	DHX40	psi-mi:“MI:0915”(physical association)	0.560
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
IARS2	GAK	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
DHX40	TRIM27	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
USP7	STIL	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
G3BP1	HAT1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CLK2	PRPF4	psi-mi:“MI:0914”(association)	0.350
TRIM52	MEIOC	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	USP27X	psi-mi:“MI:0914”(association)	0.350
CAPN12	KIF2A	psi-mi:“MI:0914”(association)	0.350
AKR7L	KIF2A	psi-mi:“MI:0914”(association)	0.350
RNF7	SOCS2	psi-mi:“MI:0914”(association)	0.350
GPSM3	PHF1	psi-mi:“MI:0914”(association)	0.350
LMNB2	SPOP	psi-mi:“MI:0914”(association)	0.350
ECE2	KDM1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (278): DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Biochemical Activity), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS), DHX40 (Affinity Capture-MS)

ESM2 similar proteins: A0A193KX02, A0A397HK53, A1Y9I9, A4IG53, A5WWC6, B6CZ46, B6CZ56, B6CZ62, B8NR70, L0TAD5, O42898, P37059, P55205, P58781, P86243, Q0IIS3, Q0P464, Q28C60, Q28DI5, Q2KHV5, Q2VQV9, Q32LS6, Q3V1F8, Q4V339, Q5JTY5, Q5RIA9, Q5XI69, Q5XI79, Q66KL0, Q68EZ3, Q6DCK1, Q6GQ37, Q6PE54, Q6Q2C2, Q6TL19, Q7L592, Q7L5L3, Q8IUF1, Q8IX18, Q8NKC1

Diamond homologs: A1Z9L3, A2A4P0, B4GEU5, B4JT42, B4K5R2, B4RC48, D4A2Z8, F4HYJ7, F4IE66, F4IJV4, F4ILR7, F4IM84, F4JMJ3, F4JRJ6, F4K2E9, F4KGU4, O17438, O22243, O22899, O35286, O42643, O42945, O43143, O45244, O46072, O51767, O60114, O60231, O70133, O94536, P0C7L7, P0CE10, P15938, P20095, P24384, P34305, P34498, P36009, P37024, P43329

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2901 predictions. Top by Δscore:

Variant	Effect	Δscore
17:59566625:A:AG	acceptor_gain	1.0000
17:59566626:G:GG	acceptor_gain	1.0000
17:59566626:GAA:G	acceptor_gain	1.0000
17:59566626:GAAGA:G	acceptor_gain	1.0000
17:59566707:GCT:G	donor_gain	1.0000
17:59566750:G:GT	donor_gain	1.0000
17:59573965:GCG:G	donor_gain	1.0000
17:59575335:TTTA:T	acceptor_loss	1.0000
17:59575336:TTAG:T	acceptor_loss	1.0000
17:59575337:TA:T	acceptor_loss	1.0000
17:59575338:A:AG	acceptor_gain	1.0000
17:59575338:AGG:A	acceptor_loss	1.0000
17:59575339:G:GG	acceptor_gain	1.0000
17:59575339:GGCC:G	acceptor_gain	1.0000
17:59575339:GGCCA:G	acceptor_gain	1.0000
17:59575467:AACAG:A	donor_loss	1.0000
17:59575468:ACAGG:A	donor_loss	1.0000
17:59575470:AG:A	donor_loss	1.0000
17:59575471:GGT:G	donor_loss	1.0000
17:59575472:G:GA	donor_loss	1.0000
17:59575473:T:A	donor_loss	1.0000
17:59577253:A:AG	acceptor_gain	1.0000
17:59577254:T:G	acceptor_gain	1.0000
17:59577255:A:AG	acceptor_gain	1.0000
17:59577256:T:G	acceptor_gain	1.0000
17:59577257:A:AG	acceptor_gain	1.0000
17:59577258:T:G	acceptor_gain	1.0000
17:59577259:A:AG	acceptor_gain	1.0000
17:59577264:A:AG	acceptor_gain	1.0000
17:59577265:G:GA	acceptor_gain	1.0000

AlphaMissense

5110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:59577308:G:C	R339T	0.999
17:59577309:A:C	R339S	0.999
17:59577309:A:T	R339S	0.999
17:59577313:T:C	C341R	0.999
17:59574245:T:C	F278L	0.998
17:59574247:T:A	F278L	0.998
17:59574247:T:G	F278L	0.998
17:59577307:A:G	R339G	0.998
17:59577315:T:G	C341W	0.998
17:59577317:T:A	V342D	0.998
17:59577322:T:C	S344P	0.998
17:59579704:G:C	A390P	0.998
17:59579726:C:A	A397D	0.998
17:59574234:A:T	D274V	0.997
17:59577308:G:T	R339I	0.997
17:59579714:G:C	R393P	0.997
17:59579751:C:G	C405W	0.997
17:59579756:G:C	R407P	0.997
17:59574213:A:G	H267R	0.996
17:59574243:T:A	V277D	0.996
17:59575373:T:C	L292P	0.996
17:59575384:G:C	A296P	0.996
17:59577310:A:G	K340E	0.996
17:59577312:A:C	K340N	0.996
17:59577312:A:T	K340N	0.996
17:59577323:C:A	S344Y	0.996
17:59577323:C:T	S344F	0.996
17:59579480:T:A	V361E	0.996
17:59579482:G:C	D362H	0.996
17:59579723:G:C	R396P	0.996

dbSNP variants (sampled 300 via entrez): RS1000083997 (17:59568458 T>A), RS1000160867 (17:59596810 A>C), RS1000296399 (17:59597162 G>A), RS1000425024 (17:59573840 C>G,T), RS1000602625 (17:59598547 A>G), RS1000769166 (17:59570442 T>C), RS1000775022 (17:59604761 A>G), RS1000801627 (17:59570182 A>G), RS1000819083 (17:59585869 G>T), RS1000837753 (17:59603208 C>A), RS1000915468 (17:59586109 G>A,T), RS1000935457 (17:59573511 T>G), RS1000955080 (17:59603203 T>A), RS1000987378 (17:59565297 C>T), RS1001007337 (17:59591609 A>G)

Disease associations

OMIM: gene MIM:607570 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465330 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	increases abundance, decreases expression, affects expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
cobaltous chloride	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1
bisphenol S	decreases methylation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression, increases abundance	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5391280	Binding	Inhibition of N-terminal thioredoxin-tagged human recombinant DHX40 transformed in Escherichia coli BL21(DE3)pLysS cells	Development of small molecule inhibitors targeting RNA helicase DHX33 as anti-cancer agents. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XN29	HAP1 DHX40 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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