DHX33

Summary

DHX33 (DEAH-box helicase 33, HGNC:16718) is a protein-coding gene on chromosome 17p13.2, encoding ATP-dependent RNA helicase DHX33 (Q9H6R0). Implicated in nucleolar organization, ribosome biogenesis, protein synthesis and cytoplasmic dsRNA sensing. It is a common-essential gene (DepMap: required in 97.1% of cancer cell lines).

This gene encodes a member of the DEAD box protein family. The DEAD box proteins are 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 56919 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 125 total
• Cancer dependency (DepMap): dependent in 97.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_020162

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16718
Approved symbol	DHX33
Name	DEAH-box helicase 33
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21972, DKFZp762F2011
Ensembl gene	ENSG00000005100
Ensembl biotype	protein_coding
OMIM	614405
Entrez	56919

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000225296, ENST00000433302, ENST00000572490, ENST00000574023, ENST00000575153

RefSeq mRNA: 2 — MANE Select: NM_020162 NM_001199699, NM_020162

CCDS: CCDS11072

Canonical transcript exons

ENST00000225296 — 12 exons

Exon	Start	End
ENSE00001061461	5463529	5463689
ENSE00001822064	5440917	5444513
ENSE00002658896	5468571	5468982
ENSE00003461421	5455997	5456182
ENSE00003476099	5462319	5462546
ENSE00003523291	5455160	5455271
ENSE00003527641	5448809	5448895
ENSE00003565509	5453821	5453980
ENSE00003588905	5450203	5450406
ENSE00003591447	5460939	5461109
ENSE00003610333	5453580	5453668
ENSE00003630897	5450807	5450934

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1005 / max 110.0044, expressed in 1737 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164032	5.1023	1641
164028	1.6440	1143
164030	1.0840	505
164031	1.0574	508
164029	0.2128	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.66	gold quality
oviduct epithelium	UBERON:0004804	94.78	gold quality
tibialis anterior	UBERON:0001385	93.33	gold quality
ileal mucosa	UBERON:0000331	90.21	gold quality
oocyte	CL:0000023	89.36	gold quality
kidney epithelium	UBERON:0004819	88.88	silver quality
deltoid	UBERON:0001476	87.00	gold quality
middle temporal gyrus	UBERON:0002771	86.94	gold quality
cauda epididymis	UBERON:0004360	86.81	gold quality
caput epididymis	UBERON:0004358	86.33	gold quality
corpus epididymis	UBERON:0004359	86.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.77	silver quality
tibia	UBERON:0000979	85.76	gold quality
upper arm skin	UBERON:0004263	84.79	gold quality
postcentral gyrus	UBERON:0002581	84.61	gold quality
cerebellar vermis	UBERON:0004720	84.58	gold quality
epithelial cell of pancreas	CL:0000083	84.34	gold quality
nipple	UBERON:0002030	84.11	gold quality
skin of hip	UBERON:0001554	83.87	gold quality
entorhinal cortex	UBERON:0002728	83.84	gold quality
parietal lobe	UBERON:0001872	83.60	gold quality
pancreatic ductal cell	CL:0002079	83.47	silver quality
cartilage tissue	UBERON:0002418	83.43	gold quality
superior frontal gyrus	UBERON:0002661	83.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.31	gold quality
esophagus squamous epithelium	UBERON:0006920	82.90	gold quality
primary visual cortex	UBERON:0002436	82.76	gold quality
fallopian tube	UBERON:0003889	82.74	gold quality
epithelium of mammary gland	UBERON:0003244	82.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting DHX33, 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-4673	100.00	66.64	1490
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-2681-5P	99.75	67.64	1655

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• we show the mechanistic importance of DHX33 in rRNA transcription and proliferation (PMID:21930779)
• results directly implicate DHX33 as a crucial player in establishing rRNA synthesis rates in the face of Ras(V12) or ARF signals, adjusting ribosome biogenesis to match the appropriate growth or antigrowth signals. (PMID:23401854)
• Data indicate that DHX33 forms the inflammasome complex with NLRP3 following stimulation with cytosolic RNA. (PMID:23871209)
• The results reveal a newly recognized function of DHX33 in mRNA translation initiation, further solidifying its central role in promoting cell growth and proliferation. (PMID:26100019)
• Our data therefore suggest DHX33 is overexpressed in HCC and serves as a promising prognostic biomarker for this deadly disease. (PMID:27073163)
• Study demonstrates that DHX33 acts as a direct transcriptional regulator to promote cell cycle progression and plays an important role in driving cell proliferation during both embryo development and tumorigenesis. (PMID:27601587)
• In clinical samples, the expression of Rab1A or DHX33 was reversely correlated with miR-634. Re-expression of Rab1A or DHX33 abrogated the miR-634-mediated inhibition of cell proliferation and migration. Collectively, our data suggest a tumor suppressor role of miR-634 in hepatocellular carcinoma. (PMID:27693040)
• High expression of DHX33 is associated with non-Hodgkin’s lymphoma and acute myeloid leukemia. (PMID:28498893)
• DHX33 doublet is due to alternative translation initiation by two in-frame initiation codons. DHX33 translation initiation from either AUG codon happens at equal efficiency. Short DHX33 protein has similar cellular location and functions with full-length DHX33. Leaky scanning normally occurs in DHX33 mRNA translation, which may serve as a safeguard mechanism to ensure optimal DHX33 translation efficiency. (PMID:29864424)
• This study highlights that DHX33 protein is critical in glioblastoma cell proliferation and its potential as a novel therapeutic drug target. (PMID:30552990)
• Results reveal that DHX33 represses apoptosis through the direct upregulation of Bcl-2 gene transcription. AP-2beta is a binding partner for DHX33 and that DHX33 acts as a coactivator for AP-2beta to promote the transcription of antiapoptotic Bcl-2 gene. (PMID:31182639)
• DHX33 is highly expressed in human colon cancers. DHX33 and Wnt/beta-catenin reciprocally regulate each other. (PMID:32004669)
• DHX33 Recruits Gadd45a To Cause DNA Demethylation and Regulates a Subset of Gene Transcription. (PMID:32312884)
• Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes. (PMID:32617965)
• Long non-coding RNA HOTAIR promotes hepatocellular carcinoma progression by regulating miR-526b-3p/DHX33 axis. (PMID:33843021)
• GSK-3beta phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation. (PMID:36403931)
• Comprehensive analysis of immune implication and prognostic value of DHX33 in sarcoma. (PMID:37115050)
• Systematic analysis of the prognostic and immunological role of DHX33 in pan-cancer. (PMID:37256545)
• RNA helicase DHX33 regulates HMGB family genes in human cancer cells. (PMID:37543097)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx33	ENSDARG00000051785
mus_musculus	Dhx33	ENSMUSG00000040620
rattus_norvegicus	Dhx33	ENSRNOG00000007054
drosophila_melanogaster	ath	FBGN0032194
caenorhabditis_elegans	let-355	WBGENE00020263

Paralogs (18): 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), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

ATP-dependent RNA helicase DHX33 — Q9H6R0 (reviewed: Q9H6R0)

Alternative names: DEAH box protein 33

All UniProt accessions (4): Q9H6R0, I3L0M5, I3L1L6, Q05BE5

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in nucleolar organization, ribosome biogenesis, protein synthesis and cytoplasmic dsRNA sensing. Stimulates RNA polymerase I transcription of the 47S precursor rRNA. Associates with ribosomal DNA (rDNA) loci where it is involved in POLR1A recruitment. In the cytoplasm, promotes elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Senses cytosolic dsRNA mediating NLRP3 inflammasome formation in macrophages and type I interferon production in myeloid dendritic cells. Required for NLRP3 activation induced by viral dsRNA and bacterial RNA. In dendritic cells, required for induction of type I interferon production induced by cytoplasmic dsRNA via the activation of MAPK and NF-kappa-B signaling pathways.

Subunit / interactions. Interacts with UBTF. Interacts with DDX3X, EIF3G and EIF3H; the interaction is independent of RNA. Interacts (via HA2 region and Helicase C-terminal domain) with the components of the large ribosomal subunit RPL3, RPL7, RPL26 and RPL27. Interacts (via DEAH box) with NLRP3 (via NACHT domain). Binds to mRNA. Binds to double-stranded RNA (via the helicase C-terminal domain). Interacts (via the helicase C-terminal domain) with MAVS.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Cytoplasm. Inflammasome.

Post-translational modifications. Ubiquitinated, leading to its degradation by the proteasome. Deubiquitinated by USP36.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H6R0-1	1	yes
Q9H6R0-2	2

RefSeq proteins (2): NP_001186628, NP_064547* (*=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 (19 total): sequence conflict 4, region of interest 3, domain 2, sequence variant 2, short sequence motif 2, compositionally biased region 2, chain 1, binding site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6R0-F1	85.90	0.58

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): 97–104

Mutagenesis-validated functional residues (1):

Position	Phenotype
103	no effect on inflammasome activation upon dsrna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 193 (showing top): GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_TRANSLATIONAL_INITIATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1

GO Biological Process (6): translational initiation (GO:0006413), positive regulation of type I interferon production (GO:0032481), positive regulation of MAPK cascade (GO:0043410), positive regulation of transcription by RNA polymerase I (GO:0045943), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227)

GO Molecular Function (14): rDNA binding (GO:0000182), RNA binding (GO:0003723), RNA helicase activity (GO:0003724), double-stranded RNA binding (GO:0003725), mRNA binding (GO:0003729), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ribosomal large subunit binding (GO:0043023), DNA-binding transcription factor binding (GO:0140297), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), NLRP3 inflammasome complex (GO:0072559), canonical inflammasome complex (GO:0061702)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	2
ATP-dependent activity	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
positive regulation of DNA-templated transcription	1
positive regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
positive regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
sequence-specific double-stranded DNA binding	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
ribonucleoside triphosphate phosphatase activity	1
ribosome binding	1
transcription factor binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
canonical inflammasome complex	1

Protein interactions and networks

STRING

2330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX33	NLRP3	Q96P20	983
DHX33	MAVS	Q7Z434	927
DHX33	DDX1	Q92499	711
DHX33	RNASEL	Q05823	664
DHX33	DDX21	Q9NR30	649
DHX33	DDX56	Q9NY93	633
DHX33	DDX60	Q8IY21	584
DHX33	DDX19A	Q9NUU7	572
DHX33	DDX24	Q9GZR7	564
DHX33	DDX3X	O00571	545
DHX33	DDX50	Q9BQ39	541
DHX33	UBTF	P17480	519
DHX33	RIGI	O95786	516
DHX33	DDX41	Q9UJV9	513
DHX33	DDX23	Q9BUQ8	501

IntAct

69 interactions, top by confidence:

A	B	Type	Score
DHX33	USP36	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
USP36	NPM1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
NPM1	WDR46	psi-mi:“MI:0914”(association)	0.480
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
PRPF4		psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
USP36	NPM1	psi-mi:“MI:0914”(association)	0.350
USP36	STK25	psi-mi:“MI:0914”(association)	0.350
PRKCB	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): DHX33 (Affinity Capture-Western), DHX33 (Biochemical Activity), TRIM33 (Affinity Capture-Western), NLRP3 (Affinity Capture-Western), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS), DHX33 (Affinity Capture-MS)

ESM2 similar proteins: A0A0L0P6P7, A4I2L4, A5PKR8, A8D8P8, A9U328, A9VB27, A9ZSZ2, D3TQJ5, F4IE66, F4ISQ7, O22899, O43143, O54747, O60126, O61660, O70157, O76922, O95985, O96651, P13099, P54358, P90829, P97283, Q07803, Q08BB1, Q0J0S6, Q13472, Q20875, Q22307, Q23223, Q4P1V1, Q5R9V1, Q5RAZ4, Q5RBD4, Q5XQC7, Q7K3M5, Q80VY9, Q8K0D5, Q8T2T7, Q96RP9

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

1 interactions.

A	Effect	B	Mechanism
USP36	“up-regulates quantity by stabilization”	DHX33	deubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
rRNA modification in the nucleus and cytosol	5	19.1×	7e-04
SARS-CoV-1-host interactions	5	17.9×	7e-04
rRNA processing in the nucleus and cytosol	5	16.4×	7e-04
rRNA processing	5	14.9×	7e-04
Major pathway of rRNA processing in the nucleolus and cytosol	11	13.9×	7e-08
Peptide chain elongation	5	12.9×	9e-04
Viral mRNA Translation	5	12.9×	9e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	5	12.8×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	8	24.6×	5e-07
cytoplasmic translation	6	15.0×	6e-04
negative regulation of translation	5	13.2×	4e-03
translation	7	9.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1749 predictions. Top by Δscore:

Variant	Effect	Δscore
17:5448803:CGATA:C	donor_loss	1.0000
17:5448804:GATA:G	donor_loss	1.0000
17:5448806:TAC:T	donor_loss	1.0000
17:5448807:ACCT:A	donor_loss	1.0000
17:5448808:C:CT	donor_loss	1.0000
17:5450197:GCTCA:G	donor_loss	1.0000
17:5450198:CTCAC:C	donor_loss	1.0000
17:5450199:TCA:T	donor_loss	1.0000
17:5450200:CACCT:C	donor_loss	1.0000
17:5450201:A:AC	donor_gain	1.0000
17:5450201:A:AT	donor_loss	1.0000
17:5450202:C:CA	donor_loss	1.0000
17:5450202:C:CC	donor_gain	1.0000
17:5450805:A:AC	donor_gain	1.0000
17:5450806:C:CC	donor_gain	1.0000
17:5450850:C:A	donor_gain	1.0000
17:5451504:A:AC	donor_gain	1.0000
17:5451505:C:CC	donor_gain	1.0000
17:5453575:CTTA:C	donor_loss	1.0000
17:5453578:A:AC	donor_gain	1.0000
17:5453578:A:AG	donor_loss	1.0000
17:5453579:C:A	donor_loss	1.0000
17:5453579:C:CT	donor_gain	1.0000
17:5453666:CAC:C	acceptor_gain	1.0000
17:5453667:ACCTG:A	acceptor_loss	1.0000
17:5453670:T:A	acceptor_loss	1.0000
17:5453816:CCTA:C	donor_loss	1.0000
17:5453817:CTAC:C	donor_loss	1.0000
17:5453818:TACC:T	donor_loss	1.0000
17:5453819:ACCTC:A	donor_loss	1.0000

AlphaMissense

4596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:5455237:G:T	A357D	1.000
17:5453881:C:G	R416P	0.999
17:5453886:G:C	C414W	0.999
17:5453887:C:T	C414Y	0.999
17:5453893:C:T	G412D	0.999
17:5453908:C:T	G407D	0.999
17:5453911:G:T	A406D	0.999
17:5453913:C:A	R405S	0.999
17:5453913:C:G	R405S	0.999
17:5453914:C:A	R405M	0.999
17:5453914:C:G	R405T	0.999
17:5453923:C:G	R402P	0.999
17:5453924:G:T	R402S	0.999
17:5453925:C:A	Q401H	0.999
17:5453925:C:G	Q401H	0.999
17:5453933:C:G	A399P	0.999
17:5455189:C:T	G373D	0.999
17:5455196:C:G	D371H	0.999
17:5455198:A:T	V370D	0.999
17:5455265:G:T	R348S	0.999
17:5456150:G:C	F294L	0.999
17:5456150:G:T	F294L	0.999
17:5456152:A:G	F294L	0.999
17:5456157:A:G	L292P	0.999
17:5462401:C:G	R199P	0.999
17:5462410:G:T	A196D	0.999
17:5462413:T:A	E195V	0.999
17:5462414:C:T	E195K	0.999
17:5462416:T:A	D194V	0.999
17:5462416:T:G	D194A	0.999

dbSNP variants (sampled 300 via entrez): RS1000230318 (17:5444585 G>A), RS1000334367 (17:5445886 C>T), RS1000342569 (17:5450770 T>C), RS1000343103 (17:5462693 TGAGA>T), RS1000450321 (17:5446128 C>T), RS1000832112 (17:5457375 C>T), RS1000835713 (17:5445816 C>A,T), RS1000950104 (17:5450962 C>G), RS1001041922 (17:5463032 T>A,C), RS1001130489 (17:5451187 C>T), RS1001221777 (17:5457294 C>A,T), RS1001308878 (17:5445442 C>T), RS1001344625 (17:5452238 G>C), RS1001547053 (17:5467860 CT>C), RS1001581968 (17:5469913 G>A)

Disease associations

OMIM: gene MIM:614405 | 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
GCST012490_579	Femur bone mineral density x serum urate levels interaction	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate 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
Acetaminophen	decreases expression	2
Estradiol	increases expression	2
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	affects cotreatment, decreases methylation	1
deoxynivalenol	increases expression	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	increases expression	1
Estrogens	decreases reaction, increases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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