DHX57

Summary

DHX57 (DExH-box helicase 57, HGNC:20086) is a protein-coding gene on chromosome 2p22.1, encoding Putative ATP-dependent RNA helicase DHX57 (Q6P158). Probable ATP-binding RNA helicase.

Enables RNA binding activity.

Source: NCBI Gene 90957 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 257 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_198963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20086
Approved symbol	DHX57
Name	DExH-box helicase 57
Location	2p22.1
Locus type	gene with protein product
Status	Approved
Aliases	DDX57
Ensembl gene	ENSG00000163214
Ensembl biotype	protein_coding
Entrez	90957

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000442331, ENST00000452978, ENST00000457308, ENST00000474104, ENST00000477981, ENST00000479345, ENST00000492042, ENST00000497514, ENST00000619207, ENST00000620517, ENST00000622155, ENST00000896807, ENST00000896808, ENST00000896809, ENST00000896810, ENST00000934861, ENST00000934862, ENST00000934863, ENST00000934864, ENST00000934865

RefSeq mRNA: 2 — MANE Select: NM_198963 NM_001329963, NM_198963

CCDS: CCDS1800

Canonical transcript exons

ENST00000457308 — 24 exons

Exon	Start	End
ENSE00003469500	38860999	38861837
ENSE00003496885	38862145	38862333
ENSE00003508799	38856340	38856461
ENSE00003515801	38863361	38863519
ENSE00003524091	38815521	38815655
ENSE00003538343	38806559	38806693
ENSE00003564915	38858661	38858836
ENSE00003567885	38819049	38819144
ENSE00003604085	38826516	38826689
ENSE00003605523	38837831	38837947
ENSE00003620409	38813821	38813895
ENSE00003621008	38802715	38802915
ENSE00003623204	38822993	38823269
ENSE00003624899	38854054	38854178
ENSE00003642471	38828340	38828436
ENSE00003645477	38818877	38818960
ENSE00003675573	38843005	38843210
ENSE00003675906	38848269	38848402
ENSE00003677960	38847019	38847073
ENSE00003682247	38825847	38826047
ENSE00003722429	38875787	38875934
ENSE00003738961	38797729	38798442
ENSE00003739735	38855057	38855252
ENSE00003745132	38868182	38868411

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3655 / max 215.3042, expressed in 1755 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27894	11.3220	1755
27892	0.0318	4
27893	0.0059	3
27891	0.0058	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.98	gold quality
buccal mucosa cell	CL:0002336	97.05	gold quality
male germ cell	CL:0000015	93.80	gold quality
right testis	UBERON:0004534	92.47	gold quality
left testis	UBERON:0004533	92.39	gold quality
cortical plate	UBERON:0005343	91.51	gold quality
ventricular zone	UBERON:0003053	90.95	gold quality
ganglionic eminence	UBERON:0004023	90.49	gold quality
tendon of biceps brachii	UBERON:0008188	90.14	gold quality
testis	UBERON:0000473	89.73	gold quality
adenohypophysis	UBERON:0002196	87.33	gold quality
monocyte	CL:0000576	87.24	gold quality
mononuclear cell	CL:0000842	87.07	gold quality
leukocyte	CL:0000738	86.99	gold quality
tibia	UBERON:0000979	86.82	gold quality
pituitary gland	UBERON:0000007	86.71	gold quality
embryo	UBERON:0000922	86.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.33	gold quality
visceral pleura	UBERON:0002401	85.31	gold quality
stromal cell of endometrium	CL:0002255	85.19	gold quality
right uterine tube	UBERON:0001302	84.99	gold quality
sural nerve	UBERON:0015488	84.68	gold quality
right adrenal gland cortex	UBERON:0035827	84.39	gold quality
granulocyte	CL:0000094	84.32	gold quality
left adrenal gland cortex	UBERON:0035825	84.15	gold quality
left adrenal gland	UBERON:0001234	84.13	gold quality
right lobe of thyroid gland	UBERON:0001119	84.12	gold quality
right ovary	UBERON:0002118	84.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.97	gold quality
adrenal cortex	UBERON:0001235	83.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx57	ENSDARG00000057660
mus_musculus	Dhx57	ENSMUSG00000035051
rattus_norvegicus	Dhx57	ENSRNOG00000054272
drosophila_melanogaster	CG1582	FBGN0030246

Paralogs (18): DHX33 (ENSG00000005100), YTHDC2 (ENSG00000047188), DHX29 (ENSG00000067248), 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), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

Putative ATP-dependent RNA helicase DHX57 — Q6P158 (reviewed: Q6P158)

Alternative names: DEAH box protein 57

All UniProt accessions (5): A0A087WW12, A0A087WZ11, Q6P158, H7BZ23, H7C109

UniProt curated annotations — full annotation on UniProt →

Function. Probable ATP-binding RNA helicase.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P158-1	1	yes
Q6P158-2	2
Q6P158-3	3

RefSeq proteins (2): NP_001316892, NP_945314* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR006575	RWD_dom	Domain
IPR007502	Helicase-assoc_dom	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR011709	DEAD-box_helicase_OB_fold	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR015940	UBA	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR042615	DHX57_UBA	Domain
IPR048333	HA2_WH	Domain
IPR059023	RNA_hel_CTD	Domain

Pfam: PF00270, PF00271, PF00642, PF04408, PF05773, PF07717, PF21010, PF26026

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (29 total): modified residue 5, splice variant 5, compositionally biased region 4, domain 3, sequence variant 3, sequence conflict 2, region of interest 2, chain 1, binding site 1, zinc finger region 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P158-F1	76.68	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): 567–574

Post-translational modifications (5): 127, 132, 475, 477, 480

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): CCAWYNNGAAR_UNKNOWN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, CACCAGC_MIR138, ACTGCAG_MIR173P, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CAGCAGG_MIR370, AAACCAC_MIR140, RFX1_02, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CAGCCTC_MIR4855P, GGATCCG_MIR127, GOBP_POSITIVE_REGULATION_OF_TRANSLATION, PARENT_MTOR_SIGNALING_UP, GOBP_REGULATION_OF_TRANSLATION

GO Biological Process (1): positive regulation of translation (GO:0045727)

GO Molecular Function (12): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), helicase activity (GO:0004386), ATP binding (GO:0005524), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), RNA polymerase binding (GO:0070063), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
binding	2
translation	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
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
enzyme binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

3000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX57	DDX54	Q8TDD1	662
DHX57	DDX46	Q7L014	576
DHX57	MLST8	Q9BVC4	518
DHX57	KIF13A	Q9H1H9	500
DHX57	DHX58	Q96C10	473
DHX57	FANCM	Q8IYD8	467
DHX57	DICER1	Q9UPY3	464
DHX57	DDX19A	Q9NUU7	450
DHX57	ARHGEF33	A8MVX0	447
DHX57	STXBP4	Q6ZWJ1	443
DHX57	NHLRC1	Q6VVB1	427
DHX57	DDX60	Q8IY21	427
DHX57	DHX34	Q14147	426
DHX57	DDX1	Q92499	424
DHX57	SCGN	O76038	418

IntAct

274 interactions, top by confidence:

A	B	Type	Score
DHX57	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
DHX57	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
DHX57	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	DHX57	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	DHX57	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	DHX57	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
	DHX57	psi-mi:“MI:0915”(physical association)	0.560
DHX57		psi-mi:“MI:0915”(physical association)	0.560
DHX57	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
DHX57	CBX2	psi-mi:“MI:0915”(physical association)	0.560
DHX57	ZNF473	psi-mi:“MI:0915”(physical association)	0.560
DHX57	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
CEP44	DHX57	psi-mi:“MI:0915”(physical association)	0.560
ZNF473	DHX57	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (328): DHX57 (Two-hybrid), DHX57 (Two-hybrid), DHX57 (Two-hybrid), DHX57 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), DHX57 (Affinity Capture-MS), DHX57 (Affinity Capture-MS), DHX57 (Affinity Capture-MS), DHX57 (Affinity Capture-MS), DHX57 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0WGX7, A2BGR3, A3KFM7, A3KMI0, A4IHD2, A4PBL4, A6QQR4, B0R061, D3Z9Z9, D3ZA12, E1B7X9, F4I2H2, F4I9Q5, F4J9M5, F4JTF6, F4K128, F8VPZ5, G5EDG2, O14139, O18017, O42861, P0CQ66, P0CQ67, P32657, P32849, P32863, P40352, P87114, Q03468, Q04692, Q0D622, Q0PCS3, Q0WVW7, Q2NKX8, Q5FWR0, Q60EX7, Q6P158, Q6PGC1, Q7F2E4, Q7Z478

Diamond homologs: A1Z9L3, A2A4P0, B3QAB0, B4JT42, B4PRJ9, B4RC48, B6IVG3, D4A2Z8, F4HYJ7, F4IE66, F4IJV4, F4ILR7, F4IM84, F4JMJ3, F4JRJ6, F4K2E9, F4KGU4, O17438, O22899, O35286, O42643, O42945, O43143, O45244, O46072, O51767, O60231, P0C7L7, P0CE10, P15938, P20095, P24384, P24785, P34305, P34498, P36009, P37024, P43329, P45018, P53131

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 162 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
Eukaryotic Translation Initiation	7	20.6×	5e-07
Cap-dependent Translation Initiation	7	20.6×	5e-07
SARS-CoV-1 modulates host translation machinery	7	20.6×	5e-07
Formation of the ternary complex, and subsequently, the 43S complex	10	20.5×	9e-10
Formation of a pool of free 40S subunits	18	19.2×	1e-16
Eukaryotic Translation Elongation	7	18.6×	1e-06
SRP-dependent cotranslational protein targeting to membrane	19	18.1×	1e-16
Peptide chain elongation	15	18.1×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	40.1×	1e-05
chromosome condensation	6	36.1×	2e-06
cytoplasmic translation	18	23.8×	3e-17
ribosomal small subunit biogenesis	11	17.9×	6e-09
translational initiation	6	15.4×	2e-04
translation	17	12.5×	1e-11
rRNA processing	11	11.1×	9e-07
regulation of alternative mRNA splicing, via spliceosome	6	10.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	208
Likely benign	16
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4262 predictions. Top by Δscore:

Variant	Effect	Δscore
2:38802713:A:AG	donor_loss	1.0000
2:38802772:T:A	donor_gain	1.0000
2:38802911:CTCAC:C	acceptor_gain	1.0000
2:38802915:CCTG:C	acceptor_loss	1.0000
2:38806594:AT:A	donor_gain	1.0000
2:38806626:G:C	donor_gain	1.0000
2:38816093:A:AC	donor_gain	1.0000
2:38816094:C:CC	donor_gain	1.0000
2:38816097:AGG:A	donor_gain	1.0000
2:38818959:CC:C	acceptor_gain	1.0000
2:38818960:CC:C	acceptor_gain	1.0000
2:38819045:TTA:T	donor_loss	1.0000
2:38819046:TA:T	donor_loss	1.0000
2:38819047:A:AC	donor_gain	1.0000
2:38819047:AC:A	donor_gain	1.0000
2:38819048:C:CT	donor_gain	1.0000
2:38819048:CC:C	donor_gain	1.0000
2:38819048:CCT:C	donor_gain	1.0000
2:38819048:CCTT:C	donor_gain	1.0000
2:38819048:CCTTA:C	donor_gain	1.0000
2:38819140:GATAC:G	acceptor_gain	1.0000
2:38819141:ATAC:A	acceptor_gain	1.0000
2:38819142:TAC:T	acceptor_gain	1.0000
2:38819143:AC:A	acceptor_gain	1.0000
2:38819143:ACC:A	acceptor_loss	1.0000
2:38819144:CC:C	acceptor_gain	1.0000
2:38819144:CCTAA:C	acceptor_loss	1.0000
2:38819145:C:CC	acceptor_gain	1.0000
2:38819145:CTAAA:C	acceptor_loss	1.0000
2:38819146:T:G	acceptor_loss	1.0000

AlphaMissense

9068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:38802853:G:C	F1293L	1.000
2:38802853:G:T	F1293L	1.000
2:38802855:A:G	F1293L	1.000
2:38806582:G:C	H1265D	1.000
2:38815603:A:G	F1175S	1.000
2:38823078:C:T	G1069D	1.000
2:38825978:C:A	R961S	1.000
2:38825978:C:G	R961S	1.000
2:38825979:C:A	R961M	1.000
2:38825979:C:G	R961T	1.000
2:38826582:G:T	A916D	1.000
2:38826672:A:G	L886P	1.000
2:38828379:A:G	L867P	1.000
2:38828420:A:C	F853L	1.000
2:38828420:A:T	F853L	1.000
2:38828422:A:G	F853L	1.000
2:38855085:C:T	G626E	1.000
2:38855133:G:T	A610D	1.000
2:38798396:A:G	L1355P	0.999
2:38798399:A:G	L1354P	0.999
2:38798420:A:G	L1347P	0.999
2:38802890:A:G	L1281P	0.999
2:38806573:A:G	S1268P	0.999
2:38806580:G:C	H1265Q	0.999
2:38806580:G:T	H1265Q	0.999
2:38806581:T:C	H1265R	0.999
2:38815602:A:C	F1175L	0.999
2:38815602:A:T	F1175L	0.999
2:38815604:A:G	F1175L	0.999
2:38815621:A:G	L1169P	0.999

dbSNP variants (sampled 300 via entrez): RS1000008139 (2:38839024 C>T), RS1000053160 (2:38821631 T>C), RS1000085753 (2:38803460 C>G), RS1000120840 (2:38805087 C>T), RS1000124861 (2:38821384 G>A), RS1000152604 (2:38845061 G>A,T), RS1000161155 (2:38827372 G>A), RS1000189556 (2:38848018 G>A,C), RS1000257920 (2:38860154 G>A,C), RS1000281182 (2:38798393 T>C), RS1000350024 (2:38870149 T>C,G), RS1000359558 (2:38839197 T>C), RS1000399898 (2:38865315 G>A,C), RS1000414809 (2:38828732 A>T), RS1000435762 (2:38865064 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_614	Obesity-related traits	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004697	estradiol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases activity, increases abundance, increases expression	3
Valproic Acid	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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