HELZ2

Summary

HELZ2 (helicase with zinc finger 2, HGNC:30021) is a protein-coding gene on chromosome 20q13.33, encoding 3’-5’ exoribonuclease HELZ2 (Q9BYK8). Can degrade highly structured RNAs through its concerted ATP-dependent RNA helicase and 3’ to 5’ exoribonuclease activities.

The protein encoded by this gene is a nuclear transcriptional co-activator for peroxisome proliferator activated receptor alpha. The encoded protein contains a zinc finger and is a helicase that appears to be part of the peroxisome proliferator activated receptor alpha interacting complex. This gene is a member of the DNA2/NAM7 helicase gene family. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 85441 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 677 total — 1 pathogenic
• MANE Select transcript: NM_001037335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30021
Approved symbol	HELZ2
Name	helicase with zinc finger 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	PDIP1, PRIC285, KIAA1769
Ensembl gene	ENSG00000130589
Ensembl biotype	protein_coding
OMIM	611265
Entrez	85441

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 retained_intron, 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370082, ENST00000427522, ENST00000467148, ENST00000478861, ENST00000479540, ENST00000850915

RefSeq mRNA: 2 — MANE Select: NM_001037335 NM_001037335, NM_033405

CCDS: CCDS33508

Canonical transcript exons

ENST00000467148 — 20 exons

Exon	Start	End
ENSE00000663486	63570504	63570611
ENSE00000991891	63569148	63569665
ENSE00000991892	63568358	63568999
ENSE00000991901	63566844	63567627
ENSE00001817615	63572108	63573221
ENSE00003481377	63570685	63570868
ENSE00003964223	63574184	63574239
ENSE00004282726	63561823	63561984
ENSE00004282727	63562072	63562203
ENSE00004282728	63566378	63566453
ENSE00004282729	63558086	63559370
ENSE00004282730	63561082	63561274
ENSE00004282731	63560171	63560327
ENSE00004282732	63561350	63561466
ENSE00004282733	63561601	63561745
ENSE00004282734	63562288	63562382
ENSE00004282735	63560479	63560697
ENSE00004282736	63559928	63560095
ENSE00004282737	63560795	63560929
ENSE00004282738	63562520	63566231

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 91.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1277 / max 411.1320, expressed in 1770 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188390	14.8796	1768
188389	0.2480	118

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.71	gold quality
bone marrow cell	CL:0002092	88.90	gold quality
blood	UBERON:0000178	85.82	gold quality
sural nerve	UBERON:0015488	84.58	gold quality
leukocyte	CL:0000738	83.93	gold quality
vermiform appendix	UBERON:0001154	83.86	gold quality
monocyte	CL:0000576	83.33	gold quality
stromal cell of endometrium	CL:0002255	83.01	gold quality
spleen	UBERON:0002106	82.86	gold quality
apex of heart	UBERON:0002098	82.49	gold quality
upper lobe of left lung	UBERON:0008952	82.28	gold quality
gall bladder	UBERON:0002110	81.55	gold quality
body of stomach	UBERON:0001161	81.14	gold quality
ileal mucosa	UBERON:0000331	81.07	gold quality
right lung	UBERON:0002167	80.93	gold quality
upper lobe of lung	UBERON:0008948	80.78	gold quality
left uterine tube	UBERON:0001303	80.60	gold quality
decidua	UBERON:0002450	80.10	gold quality
tibialis anterior	UBERON:0001385	79.74	silver quality
right lobe of liver	UBERON:0001114	79.57	gold quality
esophagus mucosa	UBERON:0002469	79.47	gold quality
lower esophagus mucosa	UBERON:0035834	79.30	gold quality
stomach	UBERON:0000945	79.20	gold quality
mucosa of stomach	UBERON:0001199	79.20	gold quality
lymph node	UBERON:0000029	79.18	gold quality
mucosa of transverse colon	UBERON:0004991	78.91	gold quality
omental fat pad	UBERON:0010414	78.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.62	gold quality
colonic epithelium	UBERON:0000397	78.61	gold quality
peritoneum	UBERON:0002358	78.58	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-53	yes	1101.94
E-ANND-3	yes	3.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting HELZ2, 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-5193	100.00	67.26	1744
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-1913	97.07	66.20	1417

Literature-anchored findings (GeneRIF, showing 5)

• Genetic polymorphisms in PRIC285 gene is associated with autoimmune disease. (PMID:22446964)
• Thrap3 could play indispensable roles in terminal differentiation of adipocytes by enhancing PPARgamma-mediated gene activation cooperatively with Helz2. (PMID:23525231)
• HELZ2 promotes K63-linked polyubiquitination of c-Myc to induce retinoblastoma tumorigenesis. (PMID:34761308)
• The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction. (PMID:36639706)
• HELZ2: a new, interferon-regulated, human 3’-5’ exoribonuclease of the RNB family is expressed from a non-canonical initiation codon. (PMID:37602378)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-183d5.1	ENSDARG00000012446
danio_rerio	helz2b	ENSDARG00000012600
danio_rerio	helz2a	ENSDARG00000016527
mus_musculus	Helz2	ENSMUSG00000027580
rattus_norvegicus	Helz2	ENSRNOG00000013267
drosophila_melanogaster	Setx	FBGN0035842
caenorhabditis_elegans		WBGENE00014208

Paralogs (10): UPF1 (ENSG00000005007), AQR (ENSG00000021776), MOV10L1 (ENSG00000073146), SETX (ENSG00000107290), ZNFX1 (ENSG00000124201), IGHMBP2 (ENSG00000132740), DNA2 (ENSG00000138346), MOV10 (ENSG00000155363), CT55 (ENSG00000169551), HELZ (ENSG00000198265)

Protein

Protein identifiers

3’-5’ exoribonuclease HELZ2 — Q9BYK8 (reviewed: Q9BYK8)

Alternative names: ATP-dependent RNA helicase PRIC285, Helicase with zinc finger 2, transcriptional coactivator, Helicase with zinc finger domain 2, PPAR-alpha-interacting complex protein 285, PPAR-gamma DNA-binding domain-interacting protein 1, Peroxisomal proliferator-activated receptor A-interacting complex 285 kDa protein

All UniProt accessions (2): Q9BYK8, A0AAA9XBX5

UniProt curated annotations — full annotation on UniProt →

Function. Can degrade highly structured RNAs through its concerted ATP-dependent RNA helicase and 3’ to 5’ exoribonuclease activities. Shows a strong preference for pyrimidine over purine residues for its nuclease activity. Acts as a transcriptional coactivator for a number of nuclear receptors including PPARA, PPARG, THRA, THRB and RXRA.

Subunit / interactions. Interacts with PPARA (via DNA-binding domain) and PPARG; the interaction stimulates the transcriptional activity of PPARA and PPARG. Interacts with THRAP3; the interaction is direct and HELZ2 and THRAP3 synergistically enhance the transcriptional activity of PPARG. It is probably part of the peroxisome proliferator activated receptor alpha interacting complex (PRIC).

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in various tissues including heart, pancreas, skeletal muscle, colon, spleen, liver, kidney, lung, peripheral blood and placenta.

Domain organisation. Contains 5 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. These motifs are not required for interaction with PPARG.

Induction. By interferon.

Similarity. Belongs to the DNA2/NAM7 helicase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYK8-1	1, PDIP1-beta	yes
Q9BYK8-2	2, PDIP1-alpha

RefSeq proteins (2): NP_001032412, NP_208384 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR001900	RNase_II/R	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR022966	RNase_II/R_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR041677	DNA2/NAM7_AAA_11	Domain
IPR041679	DNA2/NAM7-like_C	Domain
IPR047187	SF1_C_Upf1	Domain
IPR050534	Coronavir_polyprotein_1ab	Family
IPR056787	OB_HELZ2	Domain

Pfam: PF00773, PF13086, PF13087, PF25049

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (44 total): sequence variant 10, sequence conflict 8, short sequence motif 6, mutagenesis site 5, zinc finger region 4, domain 3, binding site 2, splice variant 2, region of interest 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9BYK8 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (2): 791–798; 2421–2428

Post-translational modifications (1): 1253

Mutagenesis-validated functional residues (5):

Position	Phenotype
1598	loss of 3’-5’ exoribonuclease activity. no effect on atp-dependent rna helicase activity.
1601	loss of 3’-5’ exoribonuclease activity.
1920	no effect on 3’-5’ exoribonuclease and atp-dependent rna helicase activity.
1923	no effect on 3’-5’ exoribonuclease and atp-dependent helicase activity.
2151	loss of 3’-5’ exoribonuclease activity. no effect on atp-dependent rna helicase activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-1989781	PPARA activates gene expression
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression

MSigDB gene sets: 245 (showing top): AHRARNT_01, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, CMYB_01, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, EFC_Q6, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, RICKMAN_METASTASIS_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, TGCTGAY_UNKNOWN, MODULE_171, ZIC1_01

GO Biological Process (2): regulatory ncRNA-mediated post-transcriptional gene silencing (GO:0035194), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (17): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), RNA helicase activity (GO:0003724), ATP binding (GO:0005524), zinc ion binding (GO:0008270), exoribonuclease II activity (GO:0008859), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), 3’-5’-RNA exonuclease activity (GO:0000175), helicase activity (GO:0004386), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), RNA nuclease activity (GO:0004540), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), P granule (GO:0043186)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Circadian clock	3
Regulation of lipid metabolism by PPARalpha	1
Mitochondrial biogenesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Adipogenesis	1
Metabolism of lipids	1
Cellular response to chemical stress	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of DNA-templated transcription	2
nucleic acid binding	2
catalytic activity, acting on RNA	2
ATP-dependent activity	2
catalytic activity, acting on a nucleic acid	2
nuclease activity	2
post-transcriptional gene silencing	1
regulatory ncRNA-mediated gene silencing	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
transcription coregulator activity	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
3’-5’-RNA exonuclease activity	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid conformation isomerase activity	1
hydrolase activity, acting on ester bonds	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
germ plasm	1

Protein interactions and networks

STRING

2994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HELZ2	PPARA	Q07869	761
HELZ2	CREBBP	Q92793	707
HELZ2	PARP9	Q8IXQ6	596
HELZ2	IFIT3	O14879	586
HELZ2	NCOA1	Q15788	578
HELZ2	IFI44L	Q53G44	567
HELZ2	TXNRD2	Q9NNW7	564
HELZ2	THRA	P10827	562
HELZ2	IFITM3	Q01628	552
HELZ2	IFI44	Q8TCB0	551
HELZ2	PPARD	Q03181	549
HELZ2	TRIM22	Q8IYM9	543
HELZ2	EIF2AK2	P19525	530
HELZ2	XAF1	Q6GPH4	525
HELZ2	THRB	P10828	518

IntAct

59 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
HELZ2	NUMA1	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
APOBEC3D	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CRY1	IGKV2D-30	psi-mi:“MI:0914”(association)	0.350
N	MRPL45	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
XPC	NOP56	psi-mi:“MI:0914”(association)	0.350
PACSIN2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PURG	ZNF320	psi-mi:“MI:0914”(association)	0.350
ABT1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
OASL	ZNF316	psi-mi:“MI:0914”(association)	0.350
RPS16	ZNF724	psi-mi:“MI:0914”(association)	0.350
PABPC5	APOBEC3DE	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	HECTD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-RNA), HELZ2 (Affinity Capture-MS), HELZ2 (Affinity Capture-MS), HELZ2 (Proximity Label-MS), HELZ2 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A7YSY2, D3KCC4, D3ZU57, D4A2B7, O08644, O15197, O19179, O43542, O75064, O95382, P0C0K6, P0C0K7, P51840, P52785, P52824, P54777, Q02846, Q05932, Q13470, Q13608, Q1HG60, Q3ZBE0, Q4KM32, Q5JZY3, Q643R3, Q6MG64, Q6NVG1, Q6ZPS2, Q76MJ5, Q7TNJ2, Q80SX8, Q8BYG9, Q8IZY2, Q8NFF5, Q8R5G7, Q8TDZ2, Q8WWN8, Q91V24

Diamond homologs: A0A1P8ASY1, E9QAM5, F1RCY6, O76512, P30771, P42694, Q09820, Q6DFV5, Q6NYU2, Q92900, Q98TR3, Q9BYK8, Q9EPU0, Q9FJR0, Q9HEH1, Q9VYS3, B6SFA4, D3ZG52, E1BMP7, O94247, O94387, P23249, P32644, P38935, P40694, P51530, Q00416, Q09449, Q0V8H6, Q0VGT4, Q1LXK4, Q54I89, Q57568, Q60560, Q86AS0, Q86YA3, Q8GYD9, Q8QHA5, Q8R151, Q92355

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
SARS-CoV-1 modulates host translation machinery	5	35.9×	3e-05
Nonsense-Mediated Decay (NMD)	5	27.1×	5e-05
rRNA processing in the nucleus and cytosol	6	22.4×	3e-05
rRNA processing	6	20.4×	3e-05
SARS-CoV-1-host interactions	5	20.4×	2e-04
SARS-CoV-1 Infection	5	16.6×	3e-04
Peptide chain elongation	5	14.8×	4e-04
Viral mRNA Translation	5	14.8×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	5	16.5×	5e-03
cytoplasmic translation	5	13.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	549
Likely benign	71
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
830535	NC_000020.10:g.(?61977556)(62562941_?)del	Pathogenic

SpliceAI

2600 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63559922:CCTCA:C	donor_loss	1.0000
20:63559923:CTCA:C	donor_loss	1.0000
20:63559924:TCA:T	donor_loss	1.0000
20:63559925:CAC:C	donor_loss	1.0000
20:63559927:C:CG	donor_loss	1.0000
20:63559945:T:TA	donor_gain	1.0000
20:63559972:A:AC	donor_gain	1.0000
20:63559973:C:CC	donor_gain	1.0000
20:63560006:T:TA	donor_gain	1.0000
20:63560092:CTCC:C	acceptor_gain	1.0000
20:63560094:CC:C	acceptor_gain	1.0000
20:63560095:CC:C	acceptor_gain	1.0000
20:63560095:CCTGC:C	acceptor_loss	1.0000
20:63560096:C:CC	acceptor_gain	1.0000
20:63560165:CCTCA:C	donor_loss	1.0000
20:63560166:CTCAC:C	donor_loss	1.0000
20:63560167:TCA:T	donor_loss	1.0000
20:63560168:CACCC:C	donor_loss	1.0000
20:63560169:A:AC	donor_gain	1.0000
20:63560169:AC:A	donor_gain	1.0000
20:63560170:C:CA	donor_gain	1.0000
20:63560170:C:CC	donor_gain	1.0000
20:63560170:C:G	donor_loss	1.0000
20:63560323:CGGAC:C	acceptor_gain	1.0000
20:63560328:CTGA:C	acceptor_loss	1.0000
20:63560337:C:CT	acceptor_gain	1.0000
20:63560337:C:T	acceptor_gain	1.0000
20:63560472:CACT:C	donor_loss	1.0000
20:63560473:ACTC:A	donor_loss	1.0000
20:63560474:C:CG	donor_loss	1.0000

AlphaMissense

17058 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63560067:G:C	S2562R	0.998
20:63560067:G:T	S2562R	0.998
20:63560069:T:G	S2562R	0.998
20:63566203:G:C	S873R	0.996
20:63566203:G:T	S873R	0.996
20:63566205:T:G	S873R	0.996
20:63567355:T:A	E668V	0.996
20:63568372:G:C	C572W	0.996
20:63561146:T:A	E2361V	0.995
20:63566221:G:C	F867L	0.995
20:63566221:G:T	F867L	0.995
20:63566223:A:G	F867L	0.995
20:63567358:T:A	D667V	0.995
20:63560913:T:A	D2388V	0.994
20:63567554:G:T	R602S	0.994
20:63568438:C:A	K550N	0.994
20:63568438:C:G	K550N	0.994
20:63568450:A:C	F546L	0.994
20:63568450:A:T	F546L	0.994
20:63568452:A:G	F546L	0.994
20:63559338:A:G	W2620R	0.993
20:63559338:A:T	W2620R	0.993
20:63559992:G:C	F2587L	0.993
20:63559992:G:T	F2587L	0.993
20:63559994:A:G	F2587L	0.993
20:63565008:A:G	W1272R	0.993
20:63565008:A:T	W1272R	0.993
20:63565204:G:C	C1206W	0.993
20:63565313:T:A	D1170V	0.993
20:63566085:C:A	G913W	0.993

dbSNP variants (sampled 300 via entrez): RS1000070693 (20:63566417 G>A), RS1000230439 (20:63558447 G>A,T), RS1000364542 (20:63562883 T>C), RS1000568893 (20:63564420 G>A), RS1000708819 (20:63559958 T>A,C,G), RS1001125454 (20:63566780 C>A,G,T), RS1001315218 (20:63560404 C>A,T), RS1001784938 (20:63566666 C>A,T), RS1001948564 (20:63575319 G>A,C), RS1002229039 (20:63575836 C>T), RS1002561450 (20:63574630 T>G), RS1003068950 (20:63565144 G>A), RS1003250031 (20:63560392 C>T), RS1003546186 (20:63573794 G>C), RS1003710635 (20:63558688 G>A)

Disease associations

OMIM: gene MIM:611265 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy (MONDO:0100620)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001942_22	Prostate cancer	4.000000e-16
GCST004632_79	Lymphocyte percentage of white cells	8.000000e-10
GCST010002_71	Refractive error	1.000000e-14
GCST011494_103	Daytime nap	1.000000e-12
GCST012490_477	Femur bone mineral density x serum urate levels interaction	1.000000e-09
GCST90002379_165	Basophil count	5.000000e-09
GCST90002396_70	Mean reticulocyte volume	3.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007828	daytime rest measurement
EFO:0004531	urate measurement
EFO:0005090	basophil count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, affects reaction, increases reaction, decreases expression	3
bisphenol A	affects binding, affects folding, decreases reaction	2
sodium arsenite	increases expression	2
bisphenol AF	affects folding, decreases reaction, affects binding	2
Lipopolysaccharides	increases expression, affects response to substance	2
Nickel	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
alpha phellandrene	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
bisphenol S	affects binding, decreases reaction	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Acetaminophen	increases expression	1
Aflatoxins	decreases expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Coumestrol	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1FH	Abcam A-549 HELZ2 KO 1	Cancer cell line	Male
CVCL_B2N1	Abcam A-549 HELZ2 KO 2	Cancer cell line	Male
CVCL_E1Z2	HAP1 HELZ2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).