ATOX1

Summary

ATOX1 (antioxidant 1 copper chaperone, HGNC:798) is a protein-coding gene on chromosome 5q33.1, encoding Copper transport protein ATOX1 (O00244). Binds and deliver cytosolic copper to the copper ATPase proteins.

This gene encodes a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network for later incorporation to the ceruloplasmin. This protein also functions as an antioxidant against superoxide and hydrogen peroxide, and therefore, may play a significant role in cancer carcinogenesis. Because of its cytogenetic location, this gene represents a candidate gene for 5q-syndrome.

Source: NCBI Gene 475 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_004045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:798
Approved symbol	ATOX1
Name	antioxidant 1 copper chaperone
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	HAH1
Ensembl gene	ENSG00000177556
Ensembl biotype	protein_coding
OMIM	602270
Entrez	475

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000313115, ENST00000520382, ENST00000521264, ENST00000522145, ENST00000522314, ENST00000522710, ENST00000524142, ENST00000857606, ENST00000914440, ENST00000914441, ENST00000914442

RefSeq mRNA: 1 — MANE Select: NM_004045 NM_004045

CCDS: CCDS47317

Canonical transcript exons

ENST00000313115 — 4 exons

Exon	Start	End
ENSE00001532783	151758546	151758631
ENSE00002132415	151742822	151742959
ENSE00003892073	151751704	151751779
ENSE00003893116	151746279	151746449

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 97.2275 / max 558.1106, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64435	97.2275	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.52	gold quality
right lobe of liver	UBERON:0001114	98.41	gold quality
right adrenal gland	UBERON:0001233	98.12	gold quality
right adrenal gland cortex	UBERON:0035827	98.01	gold quality
left adrenal gland cortex	UBERON:0035825	98.00	gold quality
left adrenal gland	UBERON:0001234	97.99	gold quality
left lobe of thyroid gland	UBERON:0001120	97.96	gold quality
stromal cell of endometrium	CL:0002255	97.92	gold quality
right lobe of thyroid gland	UBERON:0001119	97.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.86	gold quality
spinal cord	UBERON:0002240	97.82	gold quality
left coronary artery	UBERON:0001626	97.76	gold quality
ascending aorta	UBERON:0001496	97.70	gold quality
thoracic aorta	UBERON:0001515	97.69	gold quality
amygdala	UBERON:0001876	97.67	gold quality
metanephros cortex	UBERON:0010533	97.67	gold quality
thyroid gland	UBERON:0002046	97.60	gold quality
nucleus accumbens	UBERON:0001882	97.54	gold quality
adrenal cortex	UBERON:0001235	97.47	gold quality
coronary artery	UBERON:0001621	97.46	gold quality
descending thoracic aorta	UBERON:0002345	97.39	gold quality
right frontal lobe	UBERON:0002810	97.38	gold quality
cingulate cortex	UBERON:0003027	97.38	gold quality
lower esophagus mucosa	UBERON:0035834	97.33	gold quality
anterior cingulate cortex	UBERON:0009835	97.32	gold quality
skin of leg	UBERON:0001511	97.28	gold quality
aorta	UBERON:0000947	97.27	gold quality
right coronary artery	UBERON:0001625	97.27	gold quality
apex of heart	UBERON:0002098	97.26	gold quality
adult mammalian kidney	UBERON:0000082	97.22	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	57.07
E-MTAB-6701	yes	49.88
E-MTAB-9467	yes	47.78
E-CURD-46	yes	21.03
E-HCAD-13	yes	20.71
E-ANND-3	yes	15.60
E-MTAB-10042	yes	10.40
E-CURD-88	yes	9.23
E-MTAB-6524	no	233.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

11 targeting ATOX1, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-5002-3P	95.75	67.04	542

Literature-anchored findings (GeneRIF, showing 40)

• transfers copper to the NH2-terminal domain of the Wilson’s disease protein and regulates its catalytic activity (PMID:12029094)
• Gene structure of ATOX1. (PMID:12594858)
• A copper-dependent interaction of Atox1 with the metal binding sites of menkes protein was observed (PMID:12679332)
• X-ray absorption spectroscopy of this copper chaperone reveals a copper center capable of formation with exogenous thiols and phosphines (PMID:12686548)
• Regulates the function of ATP7B in Wilson’s disease (PMID:12763797)
• handling of copper by Atox1 and copper transfer between Atox1 and WND are under kinetic rather than thermodynamic control (PMID:14709553)
• Detailed structural and dynamic characterization of the behavior of human HAH1 in solution, in the physiologically relevant reduced apo and copper(I)-bound forms (PMID:15476398)
• interaction between the human copper(I) chaperone, HAH1, and one of its two physiological partners, the Menkes disease protein (ATP7A), was investigated in solution using heteronuclear NMR (PMID:15670166)
• Atox1 functions not only as a copper chaperone for SOD3 but also as a positive regulator for SOD3 transcription and may have an important role in modulating oxidative stress in the cardiovascular system. (PMID:15761197)
• a three-domain construct of ATP7A interacts with copper(I) and copper(I)-HAH1 (PMID:16172131)
• Wilson disease protein is an acceptor of oopper from HAH1 protein. (PMID:16571664)
• localization of ATP7A between the trans-Golgi network and the plasma membrane may be regulated by the accumulation of the adducts with HAH1, whereas the main role of domains 5 and 6 is to assist copper(I) translocation (PMID:17545667)
• The results from the quantum mechanical (QM) and MD simulations suggest that either a two- or three-coordinate exchange reaction is preferred and that it is unlikely that a four-coordinate Cu(I) species plays a role in copper exchange. (PMID:17616150)
• Divergent energetic properties of Atox1 apo- and holo-forms may be linked to conformational changes that facilitate copper transfer to the target. (PMID:17881304)
• Atox1 functions as a novel transcription factor that, when activated by copper, undergoes nuclear translocation, DNA binding, and transactivation, thereby contributing to cell proliferation. (PMID:18245776)
• No major role can be attributed to Atox1 in the pathophysiology or clinical variation of Wilson disease. (PMID:18416466)
• Forms a ocomplex with some domains of ATP7B, an interesting property of this class of proteins which have a signaling role in the function of the ATPases. (PMID:18558714)
• Conserved residues modulate copper release in human copper chaperone Atox1. (PMID:18685091)
• Atox1 residues have been conserved to ensure backbone-loop flexibility, electrostatic copper site stabilization, and proper core packing. (PMID:19146392)
• The interaction between the human copper(I)-chaperone HAH1 (human ATX1 homologue) and a metal-binding domain in one of its partners, namely the P-type copper-transporting ATPase, ATP7A, was characterized. (PMID:19453293)
• Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins: detection probes and affinity standards. (PMID:21258123)
• By binding to Atox1 in the cytoplasm, cisPt transport to DNA may be blocked. In agreement with this model, cell line studies demonstrate a correlation between Atox1 expression levels, and cisplatin resistance. (PMID:21482801)
• thermodynamic parameters of copper (Cu) transfer from the human copper chaperone Atox1 to the fourth metal-binding domain of the Wilson disease protein (PMID:22574136)
• GSSG oxidizes copper-coordinating cysteines of Atox1 with formation of an intramolecular disulfide. GSH alone is sufficient to reduce the disulfide, restoring the ability of Atox1 to bind copper; glutaredoxin 1 facilitates this reaction when GSH is low (PMID:22648419)
• No major role can be attributed to Atox1 and COMMD in the pathophysiology or clinical variation of Wilson disease. (PMID:22677543)
• different effects of ATX1 unfolding on Cu(I) affinity (PMID:23169585)
• Based on structural analysis, this work determines that the protein possesses two distinct conformations referred to as “in” and “out” due to the relative positioning of Cys12 (one of Cu(I) binding residues). (PMID:23553875)
• Knockdown of ATOX1 in non-small cell lung cancer cells was associated with reduction in copper-stimulated cell proliferation. These findings suggest that ATOX1 plays an important role in copper-stimulated proliferation of non-small cell lung cancer cells. (PMID:23624903)
• Binding of free cisplatin and reaction with the cisplatin-loaded Atox1 produce the same protein-bound platinum intermediate in the transfer of metal-binding domain (repeat) (MBD)2 from Atox1. (PMID:23751120)
• the primary coordination site of Atox1 for interaction wtih cisplatin is at the cysteine residues in the Cu(I)-binding sequence Cys(12)GlyGlyCys(15) (PMID:23778981)
• Atox1 contains positive residues that mediate membrane association and aid subsequent copper loading. (PMID:24036897)
• CTR1 silencing increased the protein levels of copper chaperone ATOX1 and copper chaperone for superoxide dismutase 1 (CCS-1), but decreased copper chaperone for cytochrome c oxidase (COX17). (PMID:24343031)
• Atox1 has a role in copper transport to tumor cell nuclei. (PMID:24445997)
• These results indicate that the roles of Atox1 in the regulation of cellular trafficking of platinum drugs are dependent on the coordination configurations. (PMID:24469739)
• Human Grx1 can catalyse reduction of Atox1 by glutathione but only in the presence of Cu(I). (PMID:24522867)
• The Cu-binding motif in Atox1, as well as in target Cu-binding domains of ATP7A/B, consists of a MX1CXXC motif where X1 = T. (PMID:24824562)
• The data collected here shows that the Atox1 keeps its dimer nature also in the presence of the CTR1 c-terminal domain; however, two geometrical states are assumed by the Atox1. (PMID:24837030)
• Cisplatin is one of the most used anticancer drugs. Its cellular influx and delivery to target DNA may involve the copper chaperone Atox1 protein. (PMID:25111319)
• Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro (PMID:25673218)
• Studied the localization of Atox1 in HeLa cells using fluorescence imaging in combination with in vitro binding experiments to fluorescently labeled DNA duplexes harboring the proposed promotor sequence. (PMID:25962064)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atox1	ENSMUSG00000018585
rattus_norvegicus	Atox1	ENSRNOG00000013118

Protein

Protein identifiers

Copper transport protein ATOX1 — O00244 (reviewed: O00244)

Alternative names: Metal transport protein ATX1

All UniProt accessions (3): E5RGN3, E5RIM7, O00244

UniProt curated annotations — full annotation on UniProt →

Function. Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense.

Subunit / interactions. Homodimer. Interacts with ATP7B. Interacts with ATP7A. Interacts (via dimer form) with SLC31A1 (via C-terminal domain); this interaction improves ATOX1 stability and controls intracellular Cu(I) levels.

Tissue specificity. Ubiquitous.

Domain organisation. The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion via the cysteine residues within the CXXC motif. The transfer of Cu(+) ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu(+)-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu(+) ion.

Similarity. Belongs to the ATX1 family.

RefSeq proteins (1): NP_004036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006121	HMA_dom	Domain
IPR017969	Heavy-metal-associated_CS	Conserved_site
IPR036163	HMA_dom_sf	Homologous_superfamily
IPR051881	Copper_transport_ATOX1-like	Family

Pfam: PF00403

UniProt features (18 total): strand 4, mutagenesis site 4, helix 2, turn 2, binding site 2, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3IWL	X-RAY DIFFRACTION	1.6
4YDX	X-RAY DIFFRACTION	1.6
1FE0	X-RAY DIFFRACTION	1.75
1FE4	X-RAY DIFFRACTION	1.75
7DC1	X-RAY DIFFRACTION	1.75
1FEE	X-RAY DIFFRACTION	1.8
3CJK	X-RAY DIFFRACTION	1.8
7ZC3	X-RAY DIFFRACTION	1.9
3IWX	X-RAY DIFFRACTION	2.14
4YEA	X-RAY DIFFRACTION	2.14
4QOT	X-RAY DIFFRACTION	2.2
5F0W	X-RAY DIFFRACTION	2.7
5T7L	X-RAY DIFFRACTION	2.83
1TL4	SOLUTION NMR
1TL5	SOLUTION NMR
2K1R	SOLUTION NMR
2LQ9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00244-F1	97.62	0.96

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): 12; 15

Post-translational modifications (2): 47, 60

Mutagenesis-validated functional residues (4):

Position	Phenotype
15	impairs cu(+)-bridged heterodimer formation with atp7a.
21	has no overall effect on cu(+)-bridged heterodimer formation with atp7a.
22	has no overall effect on cu(+)-bridged heterodimer formation with atp7a.
58	has no overall effect on cu(+)-bridged heterodimer formation with atp7a.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-6803544	Ion influx/efflux at host-pathogen interface
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2262752	Cellular responses to stress
R-HSA-6803157	Antimicrobial peptides
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 214 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, ZHAN_LATE_DIFFERENTIATION_GENES_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_RAB5A, GOBP_TRANSITION_METAL_ION_TRANSPORT, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, HSIAO_HOUSEKEEPING_GENES, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, GOBP_COPPER_ION_TRANSPORT, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (6): copper ion transport (GO:0006825), intracellular copper ion homeostasis (GO:0006878), response to oxidative stress (GO:0006979), negative regulation of apoptotic process (GO:0043066), copper ion export (GO:0060003), monoatomic ion transport (GO:0006811)

GO Molecular Function (8): copper ion binding (GO:0005507), metallochaperone activity (GO:0016530), copper chaperone activity (GO:0016531), copper-dependent protein binding (GO:0032767), ATPase binding (GO:0051117), cuprous ion binding (GO:1903136), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cellular response to chemical stress	1
Antimicrobial peptides	1
Immune System	1
Cellular responses to stimuli	1
Innate Immune System	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
copper ion binding	2
transition metal ion transport	1
intracellular monoatomic cation homeostasis	1
copper ion homeostasis	1
response to stress	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
copper ion transmembrane transport	1
transport	1
transition metal ion binding	1
metal ion binding	1
molecular carrier activity	1
metallochaperone activity	1
protein binding	1
enzyme binding	1
binding	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATOX1	ATP7B	P35670	981
ATOX1	ATP7A	Q04656	978
ATOX1	CCS	O14618	950
ATOX1	COX17	Q14061	945
ATOX1	SOD1	P00441	915
ATOX1	SLC31A1	O15431	883
ATOX1	SCO2	O43819	821
ATOX1	COMMD1	Q8N668	813
ATOX1	SLC31A2	O15432	810
ATOX1	SCO1	O75880	789
ATOX1	COX11	Q9Y6N1	777
ATOX1	PRDX3	P30048	761
ATOX1	CP	P00450	723
ATOX1	GLRX	P35754	693
ATOX1	CHCHD4	Q8N4Q1	670

IntAct

33 interactions, top by confidence:

A	B	Type	Score
FAM118A	ATOX1	psi-mi:“MI:0915”(physical association)	0.720
ATOX1	FAM118A	psi-mi:“MI:0915”(physical association)	0.720
CFAP410	ATOX1	psi-mi:“MI:0915”(physical association)	0.560
GGPS1	ATOX1	psi-mi:“MI:0915”(physical association)	0.560
ATOX1	GGPS1	psi-mi:“MI:0915”(physical association)	0.560
ATOX1	COMP	psi-mi:“MI:0915”(physical association)	0.560
ATOX1	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
ATOX1	ATP7B	psi-mi:“MI:0915”(physical association)	0.540
ATOX1	ATP7B	psi-mi:“MI:0407”(direct interaction)	0.540
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
HTRA4	ATOX1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
INSR	ATOX1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
ATP7A	ATOX1	psi-mi:“MI:2364”(proximity)	0.270
LOX	ATOX1	psi-mi:“MI:2364”(proximity)	0.270
ATOX1	COMP	psi-mi:“MI:0915”(physical association)	0.000
ATOX1	NECAB1	psi-mi:“MI:0915”(physical association)	0.000
ATOX1	FAM118A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): C21orf2 (Two-hybrid), GGPS1 (Two-hybrid), FAM118A (Two-hybrid), ATOX1 (Co-fractionation), ATOX1 (Co-fractionation), ATOX1 (Co-fractionation), ATOX1 (Co-fractionation), ATOX1 (Co-fractionation), ATOX1 (Co-fractionation), ATOX1 (Co-fractionation), GSTT1 (Co-fractionation), ATOX1 (Affinity Capture-RNA), ATOX1 (Two-hybrid), ATOX1 (Two-hybrid), ATOX1 (Two-hybrid)

ESM2 similar proteins: B0BN85, B4G0F3, B8BKI7, C6JS30, O00244, O08997, O74735, O76003, O81187, P07178, P07311, P13439, P19356, P22907, P24540, P31754, P38636, P41500, P55142, P55143, P56376, Q0V9A9, Q28C69, Q28ID3, Q2KIK0, Q2R483, Q3T0E0, Q53H82, Q54PZ2, Q5R514, Q5RAL9, Q5XGR8, Q5XJ54, Q5XK67, Q61035, Q6DBT3, Q8L8T2, Q8W1X2, Q94BT9, Q96EK6

Diamond homologs: O00244, O08997, O74735, Q3T0E0, Q54PZ2, Q6PWT7, Q7XTY9, Q9LD47, Q9TT99, Q9WU84, Q9WUC4, Q9XT28, O82089, Q94BT9, Q9JK72, P38636, A2RVM8, A5IVY3, A5IVY4, A6QK47, A6QK48, A6U4T8, A6U4T9, A7X6S1, A7X6S3, A8Z3F8, A8Z3F9, B3H6D0, P0C885, Q2FDU9, Q2FDV0, Q2FV63, Q2FV64, Q2YWA3, Q4A0G1, Q5HCZ2, Q5HCZ3, Q6G6B6, Q6G6B7, Q6GDP0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1718 predictions. Top by Δscore:

Variant	Effect	Δscore
5:151746331:AAGG:A	donor_gain	1.0000
5:151746355:T:A	donor_gain	1.0000
5:151751700:TCAC:T	donor_loss	1.0000
5:151751701:CACCT:C	donor_loss	1.0000
5:151751702:A:C	donor_loss	1.0000
5:151772412:C:A	donor_gain	1.0000
5:151744842:T:TA	donor_gain	0.9900
5:151744843:C:A	donor_gain	0.9900
5:151746296:T:TA	donor_gain	0.9900
5:151746331:AAGGC:A	donor_gain	0.9900
5:151746447:CTC:C	acceptor_gain	0.9900
5:151751698:A:AC	donor_gain	0.9900
5:151751699:C:CC	donor_gain	0.9900
5:151751702:ACCT:A	donor_gain	0.9900
5:151751703:CCTC:C	donor_gain	0.9900
5:151751777:CTT:C	acceptor_gain	0.9900
5:151751780:C:CC	acceptor_gain	0.9900
5:151766358:C:CC	acceptor_gain	0.9900
5:151772028:GCCGC:G	donor_gain	0.9900
5:151746331:A:AC	donor_gain	0.9800
5:151746332:A:C	donor_gain	0.9800
5:151746449:CCTG:C	acceptor_loss	0.9800
5:151746450:C:CA	acceptor_loss	0.9800
5:151746451:T:C	acceptor_loss	0.9800
5:151751697:CACT:C	donor_loss	0.9800
5:151751698:ACTC:A	donor_loss	0.9800
5:151751703:CCT:C	donor_gain	0.9800
5:151751775:TGCTT:T	acceptor_gain	0.9800
5:151751778:TT:T	acceptor_gain	0.9800
5:151765625:A:C	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000023217 (5:151743840 T>C,G), RS1000084165 (5:151749846 C>G,T), RS1000176831 (5:151757962 CG>C,CGG), RS1000754403 (5:151758250 C>A), RS1000792448 (5:151756067 G>A), RS1000851255 (5:151751085 C>T), RS1001066430 (5:151745425 C>T), RS1001089371 (5:151751279 A>T), RS1001129012 (5:151751630 C>T), RS1001435237 (5:151745101 A>G), RS1001523883 (5:151747983 T>C,G), RS1001591821 (5:151743567 G>T), RS1001759683 (5:151756869 T>C), RS1001991757 (5:151754940 G>A,C), RS1002062876 (5:151754547 A>G)

Disease associations

OMIM: gene MIM:602270 | disease phenotypes: MIM:149400

GenCC curated gene-disease

Mondo (1): hereditary hyperekplexia (MONDO:0021022)

Orphanet (1): Hereditary hyperekplexia (Orphanet:3197)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003825_5	Systolic blood pressure change trajectory	1.000000e-08
GCST005984_17	Glomerular filtration rate	2.000000e-08
GCST005985_19	Creatinine levels	1.000000e-09
GCST90002404_218	Red cell distribution width	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006944	systolic blood pressure change measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Copper	affects transport, affects binding, decreases reaction, increases abundance, increases expression (+4 more)	11
bisphenol A	decreases methylation, increases expression, affects expression, decreases expression	4
Valproic Acid	increases expression, affects expression	4
Cisplatin	increases metabolic processing, increases reaction, increases expression, affects binding	3
sodium arsenite	affects expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
lead acetate	increases expression	1
arsenite	affects binding, increases reaction	1
1,6-hexamethylene diisocyanate	increases methylation	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium bisulfide	decreases expression, decreases reaction	1
cupric chloride	increases expression, decreases response to substance, increases abundance	1
tetraethylenepentamine	increases expression	1
cyfluthrin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cuprous sulfide	decreases expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
trans-(PtCl2(NH3)(thiazole))	affects binding, increases reaction	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Oxaliplatin	affects response to substance	1
Air Pollutants	increases abundance, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2SC	Abcam HEK293T ATOX1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01476514	Not specified	TERMINATED	Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing
NCT05168969	Not specified	COMPLETED	Hyperekplexia in Patients With CTNNB1 Mutation
NCT05652101	Not specified	RECRUITING	Hyperekplexia : Adaptative Skills and Neurodevelopmental Trajectory
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening