HELZ

Summary

HELZ (helicase with zinc finger, HGNC:16878) is a protein-coding gene on chromosome 17q24.2, encoding ATP-dependent RNA helicase with zinc finger domain (P42694). ATP-dependent RNA helicase that promotes degradation of mRNAs via its association with the CCR4-NOT deadenylase complex, leading to deadenylation, decapping, and subsequent degradation of target mRNAs.

HELZ is a member of the superfamily I class of RNA helicases. RNA helicases alter the conformation of RNA by unwinding double-stranded regions, thereby altering the biologic activity of the RNA molecule and regulating access to other proteins (Wagner et al., 1999 [PubMed 10471385]).

Source: NCBI Gene 9931 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 246 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_014877

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16878
Approved symbol	HELZ
Name	helicase with zinc finger
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0054, HUMORF5, DHRC
Ensembl gene	ENSG00000198265
Ensembl biotype	protein_coding
OMIM	606699
Entrez	9931

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 non_stop_decay, 1 nonsense_mediated_decay

ENST00000358691, ENST00000417253, ENST00000578783, ENST00000578938, ENST00000579861, ENST00000579953, ENST00000580168, ENST00000580662, ENST00000580963, ENST00000581159, ENST00000582864, ENST00000584641, ENST00000873041, ENST00000873042, ENST00000913195, ENST00000913196, ENST00000913197, ENST00000913198, ENST00000913199

RefSeq mRNA: 2 — MANE Select: NM_014877 NM_001330447, NM_014877

CCDS: CCDS42374, CCDS82192

Canonical transcript exons

ENST00000358691 — 33 exons

Exon	Start	End
ENSE00000947857	67195419	67195470
ENSE00000947858	67193967	67194042
ENSE00000947859	67190157	67190355
ENSE00000947860	67189589	67189696
ENSE00000947861	67188319	67188616
ENSE00000947864	67166478	67166608
ENSE00000947865	67160897	67161076
ENSE00000947867	67151046	67151224
ENSE00000947868	67149867	67149985
ENSE00000947869	67148569	67148714
ENSE00000947870	67145743	67145890
ENSE00000947871	67137931	67138114
ENSE00000947872	67135970	67136198
ENSE00000947873	67128651	67128855
ENSE00001149266	67070444	67078586
ENSE00001149273	67167463	67167796
ENSE00001178752	67160261	67160362
ENSE00001361489	67239433	67239489
ENSE00001361503	67243784	67243839
ENSE00003481239	67109116	67109686
ENSE00003483335	67218595	67218822
ENSE00003504436	67123963	67124014
ENSE00003519992	67120405	67120612
ENSE00003525614	67086829	67087081
ENSE00003555857	67203319	67203443
ENSE00003568931	67178659	67178926
ENSE00003587869	67122970	67123160
ENSE00003591232	67107169	67107685
ENSE00003611765	67215899	67215935
ENSE00003654621	67114324	67114403
ENSE00003676370	67108492	67108726
ENSE00003690119	67201129	67201185
ENSE00003844132	67245148	67245196

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 95.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.7930 / max 531.0837, expressed in 1799 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167681	28.8036	1797
167683	1.0133	504
167674	0.6838	306
167682	0.1830	100
167678	0.0986	28
167679	0.0107	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	95.22	gold quality
calcaneal tendon	UBERON:0003701	95.20	gold quality
secondary oocyte	CL:0000655	94.68	gold quality
adrenal tissue	UBERON:0018303	94.49	gold quality
oocyte	CL:0000023	93.48	gold quality
bone marrow cell	CL:0002092	93.39	gold quality
deltoid	UBERON:0001476	92.01	silver quality
tibialis anterior	UBERON:0001385	92.00	gold quality
corpus callosum	UBERON:0002336	90.82	gold quality
cardia of stomach	UBERON:0001162	90.76	gold quality
bone marrow	UBERON:0002371	90.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.30	gold quality
caput epididymis	UBERON:0004358	90.03	gold quality
superficial temporal artery	UBERON:0001614	89.84	gold quality
ileal mucosa	UBERON:0000331	89.75	gold quality
trabecular bone tissue	UBERON:0002483	89.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.24	gold quality
pylorus	UBERON:0001166	88.96	gold quality
upper leg skin	UBERON:0004262	88.93	gold quality
endometrium epithelium	UBERON:0004811	88.85	gold quality
tibia	UBERON:0000979	88.75	gold quality
corpus epididymis	UBERON:0004359	88.74	gold quality
tonsil	UBERON:0002372	88.72	gold quality
biceps brachii	UBERON:0001507	88.52	gold quality
cauda epididymis	UBERON:0004360	88.45	gold quality
mononuclear cell	CL:0000842	87.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.96	gold quality
monocyte	CL:0000576	87.95	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.95	gold quality
CA1 field of hippocampus	UBERON:0003881	87.74	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

287 targeting HELZ, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 2)

• Results suggest that loss of expression of DRHC may play a role in human carcinogenesis. (PMID:12691822)
• Downregulation of HELZ reduced translational initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of ribosomal protein S6. (PMID:21765940)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	helz	ENSDARG00000030560
mus_musculus	Helz	ENSMUSG00000020721
rattus_norvegicus	Helz	ENSRNOG00000003213
drosophila_melanogaster	Helz	FBGN0036451
caenorhabditis_elegans	Y106G6D.5	WBGENE00014965
caenorhabditis_elegans	sosi-1	WBGENE00016565
caenorhabditis_elegans	eri-7	WBGENE00016566

Paralogs (10): UPF1 (ENSG00000005007), AQR (ENSG00000021776), MOV10L1 (ENSG00000073146), SETX (ENSG00000107290), ZNFX1 (ENSG00000124201), HELZ2 (ENSG00000130589), IGHMBP2 (ENSG00000132740), DNA2 (ENSG00000138346), MOV10 (ENSG00000155363), CT55 (ENSG00000169551)

Protein

Protein identifiers

ATP-dependent RNA helicase with zinc finger domain — P42694 (reviewed: P42694)

Alternative names: Down-regulated in human cancers protein

All UniProt accessions (6): A0A075B6R3, P42694, J3KS59, J3KT20, J3QRR8, J3QS41

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent RNA helicase that promotes degradation of mRNAs via its association with the CCR4-NOT deadenylase complex, leading to deadenylation, decapping, and subsequent degradation of target mRNAs. Can repress translation independently of mRNA decay in a manner dependent on both the CCR4-NOT complex and the helicase DDX6. Involved in promoting cell proliferation, translation initiation, and ribosomal protein S6 (RPS6) phosphorylation.

Subunit / interactions. Interacts with SMYD2. Interacts with POLR2A. Interacts with SMYD3; the interaction may bridge SMYD3 and RNA polymerase II. Interacts with PAN3, EDC4, PATL1 and with CCR4-NOT complex components CNOT1 and CNOT3. Interacts (via the PAM2 motif) with PABPC1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed predominantly in thymus and brain. Expression is down-regulated in 28 of 95 tested cancer cell lines.

Similarity. Belongs to the DNA2/NAM7 helicase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P42694-1	1	yes
P42694-2	2

RefSeq proteins (2): NP_001317376, NP_055692* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR014016	UvrD-like_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR041677	DNA2/NAM7_AAA_11	Domain
IPR041679	DNA2/NAM7-like_C	Domain
IPR045055	DNA2/NAM7-like	Family
IPR047187	SF1_C_Upf1	Domain
IPR049569	HELZ_DEAD-box_1	Domain

Pfam: PF00580, PF00642, PF13086, PF13087

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (42 total): region of interest 10, compositionally biased region 10, modified residue 8, short sequence motif 3, splice variant 3, sequence variant 3, mutagenesis site 2, chain 1, zinc finger region 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42694-F1	59.24	0.20

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): 668–675

Post-translational modifications (8): 248, 1163, 1245, 1614, 1645, 1738, 1741, 1766

Mutagenesis-validated functional residues (2):

Position	Phenotype
1107	loss of interaction with pabpc1.
1107	loss of interaction with pabpc1 but no effect on its ability to induce mrna degradation and deadenylation-independent tr

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_229, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_DEADENYLATION_DEPENDENT_DECAY

GO Biological Process (4): positive regulation of cell population proliferation (GO:0008284), negative regulation of translation (GO:0017148), regulatory ncRNA-mediated post-transcriptional gene silencing (GO:0035194), positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153)

GO Molecular Function (10): RNA binding (GO:0003723), helicase activity (GO:0004386), ATP binding (GO:0005524), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), CCR4-NOT complex binding (GO:1905762), nucleotide binding (GO:0000166), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), P granule (GO:0043186)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleic acid binding	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
post-transcriptional gene silencing	1
regulatory ncRNA-mediated gene silencing	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
positive regulation of mRNA catabolic process	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
ATP-dependent activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
catalytic activity	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
germ plasm	1

Protein interactions and networks

STRING

1568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HELZ	SMYD3	Q9H7B4	946
HELZ	NKX2-8	O15522	827
HELZ	CNOT1	A5YKK6	667
HELZ	HSCB	Q8IWL3	548
HELZ	PITPNC1	Q9UKF7	537
HELZ	GTF2E2	P29084	517
HELZ	LYRM7	Q5U5X0	499
HELZ	PATL1	Q86TB9	458
HELZ	ATXN2L	Q8WWM7	452
HELZ	HSP90AA1	P07900	446
HELZ	LYRM9	A8MSI8	424
HELZ	RC3H2	Q9HBD1	422
HELZ	SMYD2	Q9NRG4	420
HELZ	DEAF1	O75398	417
HELZ	SMYD5	Q6GMV2	398

IntAct

166 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
RACK1	HELZ	psi-mi:“MI:0914”(association)	0.770
RACK1	HELZ	psi-mi:“MI:0915”(physical association)	0.770
WRAP53	TCP1	psi-mi:“MI:0914”(association)	0.690
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RACK1	RIOK3	psi-mi:“MI:0914”(association)	0.640
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
HSCB	NQO2	psi-mi:“MI:0914”(association)	0.550
HSCB	HELZ	psi-mi:“MI:0915”(physical association)	0.550
CELA3A	POTEF	psi-mi:“MI:0914”(association)	0.530
BCAT1	ARNT	psi-mi:“MI:0914”(association)	0.530
PIGT	ZNF609	psi-mi:“MI:0914”(association)	0.530
HCFC2	SETD1A	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
PRKAG3	PFDN6	psi-mi:“MI:0914”(association)	0.530
ANGPTL7	TCP1	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
CLTC		psi-mi:“MI:0914”(association)	0.350
SEC16A	NCOR2	psi-mi:“MI:0914”(association)	0.350
Lgals3bp	CS	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A0G2QC33, A0FKG7, A6H7H7, F1N9S8, O95453, P0C0T1, P42694, P50747, P69341, Q0IIH8, Q0VGM9, Q13572, Q28559, Q4R528, Q5BJZ6, Q5F480, Q5R699, Q5RC51, Q5ZIA0, Q5ZIW7, Q640G7, Q6DDJ3, Q6DFV5, Q6DG88, Q6DJB3, Q6GR37, Q6NYU2, Q6PZ02, Q6PZ03, Q6PZ05, Q7T0P6, Q80UY1, Q80YV4, Q811C2, Q8BGE6, Q8BYN3, Q8C9S8, Q8N4J0, Q8VDG3, Q8WYN0

Diamond homologs: A0A1P8ASY1, E9QAM5, F1RCY6, O76512, P30771, P42694, Q09820, Q6DFV5, Q6NYU2, Q92900, Q98TR3, Q9BYK8, Q9EPU0, Q9FJR0, Q9HEH1, Q9VYS3, Q8GYD9, Q99MV5, P23249, Q0V8H6, Q0VGT4, Q1LXK4, Q1LXK5, Q54I89, Q5ZKD7, Q6J5K9, Q86YA3, Q9BXT6, Q9HCE1, O94387, Q92355, B6SFA4, D3ZG52, O94247, P40694, Q6ZQJ5, Q86AS0, Q9EQN5, A2AKX3, P34243

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transport	7	10.8×	1e-03
negative regulation of translation	8	9.2×	1e-03
mRNA processing	12	5.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	197
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
402158	NM_014877.4(HELZ):c.3322A>G (p.Ile1108Val)	Likely pathogenic

SpliceAI

5740 predictions. Top by Δscore:

Variant	Effect	Δscore
17:67087077:TCATA:T	acceptor_gain	1.0000
17:67087078:CATA:C	acceptor_gain	1.0000
17:67087078:CATAC:C	acceptor_gain	1.0000
17:67087079:ATA:A	acceptor_gain	1.0000
17:67087080:TA:T	acceptor_gain	1.0000
17:67087080:TAC:T	acceptor_loss	1.0000
17:67087082:C:A	acceptor_loss	1.0000
17:67087082:C:CC	acceptor_gain	1.0000
17:67087083:T:G	acceptor_loss	1.0000
17:67114318:GCATA:G	donor_loss	1.0000
17:67114319:CATA:C	donor_loss	1.0000
17:67114320:ATAC:A	donor_loss	1.0000
17:67114321:TA:T	donor_loss	1.0000
17:67114322:ACC:A	donor_loss	1.0000
17:67114323:CC:C	donor_loss	1.0000
17:67114400:TTACC:T	acceptor_loss	1.0000
17:67114401:TACCT:T	acceptor_loss	1.0000
17:67114402:ACCTA:A	acceptor_loss	1.0000
17:67114404:C:T	acceptor_loss	1.0000
17:67114405:T:G	acceptor_loss	1.0000
17:67120400:CTT:C	donor_gain	1.0000
17:67120400:CTTA:C	donor_loss	1.0000
17:67120401:TTA:T	donor_gain	1.0000
17:67120402:TA:T	donor_loss	1.0000
17:67120402:TAC:T	donor_gain	1.0000
17:67120403:A:AC	donor_gain	1.0000
17:67120403:AC:A	donor_gain	1.0000
17:67120403:ACCA:A	donor_loss	1.0000
17:67120404:C:CT	donor_gain	1.0000
17:67120404:CC:C	donor_gain	1.0000

AlphaMissense

12765 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:67128717:A:C	F1107L	1.000
17:67128717:A:T	F1107L	1.000
17:67128718:A:C	F1107C	1.000
17:67128718:A:G	F1107S	1.000
17:67128719:A:G	F1107L	1.000
17:67128739:A:G	L1100S	1.000
17:67128825:A:C	C1071W	1.000
17:67128826:C:T	C1071Y	1.000
17:67128846:C:A	W1064C	1.000
17:67128846:C:G	W1064C	1.000
17:67128848:A:G	W1064R	1.000
17:67128848:A:T	W1064R	1.000
17:67135972:G:C	C1060W	1.000
17:67135974:A:G	C1060R	1.000
17:67135979:C:T	G1058E	1.000
17:67135980:C:G	G1058R	1.000
17:67135980:C:T	G1058R	1.000
17:67135991:A:G	L1054P	1.000
17:67135994:G:T	A1053D	1.000
17:67136003:T:C	D1050G	1.000
17:67136006:C:A	G1049V	1.000
17:67136006:C:T	G1049D	1.000
17:67136007:C:A	G1049C	1.000
17:67136007:C:G	G1049R	1.000
17:67136015:G:T	A1046D	1.000
17:67136018:A:T	V1045D	1.000
17:67136021:A:G	L1044P	1.000
17:67136025:A:G	S1043P	1.000
17:67136032:T:A	R1040S	1.000
17:67136032:T:G	R1040S	1.000

dbSNP variants (sampled 300 via entrez): RS1000011650 (17:67155639 C>A,T), RS1000020750 (17:67077820 C>T), RS1000030591 (17:67077531 T>C), RS1000054868 (17:67201508 A>G), RS1000081050 (17:67103261 A>T), RS1000104945 (17:67237278 C>A,G), RS1000108037 (17:67167671 T>G), RS1000111945 (17:67148423 A>G), RS1000115772 (17:67210061 T>C), RS1000117838 (17:67162603 A>C,G), RS1000142943 (17:67148754 T>A,C), RS1000155607 (17:67116378 G>A), RS1000169321 (17:67071731 T>C), RS1000173147 (17:67090169 T>C), RS1000208305 (17:67109850 A>T)

Disease associations

OMIM: gene MIM:606699 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): pervasive developmental disorder (MONDO:0000594)

Orphanet (1): Rare pervasive developmental disorder (Orphanet:168778)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005083_7	Putamen volume	1.000000e-06
GCST008473_2	Visceral fat	2.000000e-06
GCST90002388_504	Lymphocyte count	5.000000e-09
GCST90002389_239	Lymphocyte percentage of white cells	7.000000e-11
GCST90002399_249	Neutrophil percentage of white cells	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002659	Child Development Disorders, Pervasive	F03.625.164

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066901 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.03	Kd	9.391	nM	CHEMBL3752910
8.03	ED50	9.391	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149867: Binding affinity to human HELZ incubated for 45 mins by Kinobead based pull down assay	kd	0.0094	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
jinfukang	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Diazinon	increases methylation	1
Ethyl Methanesulfonate	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
CHEMBL5652909	Binding	Binding affinity to human HELZ incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5EH	HEK293T-HELZ-null	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205699	PHASE4	COMPLETED	Metabolic Effects of Antipsychotics in Children
NCT01238575	PHASE4	COMPLETED	Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT00399698	PHASE3	COMPLETED	Study to Determine Whether There Are Any Cognitive or Motor Effects From Taking the Medicine Risperidone.
NCT00870727	PHASE3	COMPLETED	Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT00198055	PHASE2	COMPLETED	A Study of Aripiprazole in Children and Adolescents With Aspergers and Pervasive Developmental Disorder.
NCT00308074	PHASE2	COMPLETED	An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders
NCT01602016	PHASE2	TERMINATED	A Folinic Acid Intervention for Autism Spectrum Disorders
NCT05664841	PHASE2	RECRUITING	The Impact of a Virtual Magic Trick Training Program
NCT00325572	PHASE1	TERMINATED	Evaluation and Treatment of Copper/Zinc Imbalance in Children With Autism
NCT00773812	PHASE1	COMPLETED	Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders
NCT01243905	PHASE2/PHASE3	UNKNOWN	Group Psychoeducational Program for Mothers of Children With High Functional Pervasive Developmental Disorders
NCT00318162	PHASE1/PHASE2	UNKNOWN	Trial of Low-Dose Naltrexone for Children With Pervasive Developmental Disorder (PDD)
NCT00004458	Not specified	TERMINATED	Longitudinal and Biological Study of Childhood Disintegrative Disorder
NCT00025779	Not specified	COMPLETED	Methylphenidate in Children and Adolescents With Pervasive Developmental Disorders
NCT00464477	Not specified	COMPLETED	Advanced Grandparental Age as a Risk Factor for Autism
NCT00531830	Not specified	UNKNOWN	Assessment of Factors Which Predict Improvement in Children With PDD After a Year of Integrative Therapy
NCT00579267	Not specified	COMPLETED	Reliability and Validity of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)
NCT00902798	Not specified	COMPLETED	Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder
NCT01160783	Not specified	ACTIVE_NOT_RECRUITING	Genetic Contributions to Autism Spectrum Disorders
NCT01553240	Not specified	TERMINATED	Neurocircuitry of Autism- fMRI and Transcranial Magnetic Stimulation Studies
NCT01631851	Not specified	COMPLETED	Cognitive-Behavioral Therapy for Irritability in Adolescents With High Functioning Autism Spectrum Disorder
NCT01808066	Not specified	COMPLETED	GroundsKeeper: A Qualitative Study of Applied Game-based Interactives in Special Education Programs
NCT01921244	Not specified	COMPLETED	Shared Decision Making to Improve Care and Outcomes for Children With Autism
NCT03170453	Not specified	COMPLETED	Confirmatory Efficacy Trial of Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder
NCT03177590	Not specified	COMPLETED	Recording Facial and Vocal Emotional Productions in Children With Autism as Part of the JEMImE Project
NCT03560453	Not specified	COMPLETED	Facilitating Employment for Youth With Autism
NCT03602378	Not specified	UNKNOWN	QoL and Stress in Parents of Children With Developmental Disabilities and Chronic Disease
NCT04654260	Not specified	ACTIVE_NOT_RECRUITING	Behavior Therapy for Irritability in Autism
NCT04788537	Not specified	COMPLETED	Services to Enhance Social Functioning in Adults With Autism Spectrum Disorders