CIZ1

Summary

CIZ1 (CDKN1A interacting zinc finger protein 1, HGNC:16744) is a protein-coding gene on chromosome 9q34.11, encoding Cip1-interacting zinc finger protein (Q9ULV3). May regulate the subcellular localization of CIP/WAF1.

The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 25792 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dystonia 23 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 530 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 17
• MANE Select transcript: NM_001131016

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16744
Approved symbol	CIZ1
Name	CDKN1A interacting zinc finger protein 1
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	LSFR1, ZNF356
Ensembl gene	ENSG00000148337
Ensembl biotype	protein_coding
OMIM	611420
Entrez	25792

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 34 protein_coding, 14 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000277465, ENST00000324544, ENST00000357558, ENST00000372938, ENST00000372948, ENST00000372954, ENST00000415526, ENST00000420484, ENST00000461765, ENST00000467178, ENST00000471773, ENST00000471839, ENST00000474442, ENST00000475471, ENST00000476239, ENST00000476541, ENST00000476727, ENST00000485001, ENST00000485862, ENST00000488559, ENST00000491487, ENST00000491954, ENST00000498156, ENST00000538431, ENST00000629610, ENST00000634501, ENST00000634901, ENST00000651955, ENST00000866500, ENST00000866501, ENST00000866502, ENST00000866503, ENST00000866504, ENST00000866505, ENST00000866506, ENST00000866507, ENST00000866508, ENST00000866509, ENST00000866510, ENST00000866511, ENST00000866512, ENST00000866513, ENST00000937742, ENST00000937743, ENST00000965482, ENST00000965483, ENST00000965484, ENST00000965485, ENST00000965486

RefSeq mRNA: 7 — MANE Select: NM_001131016 NM_001131015, NM_001131016, NM_001131017, NM_001131018, NM_001257975, NM_001257976, NM_012127

CCDS: CCDS48033, CCDS48034, CCDS59147, CCDS6894, CCDS75910

Canonical transcript exons

ENST00000372938 — 17 exons

Exon	Start	End
ENSE00001109798	128178709	128179415
ENSE00001228966	128177566	128177763
ENSE00003476396	128178369	128178490
ENSE00003477285	128185547	128185776
ENSE00003490393	128169406	128169519
ENSE00003496048	128170020	128170107
ENSE00003506440	128187863	128187934
ENSE00003531815	128166759	128166880
ENSE00003564330	128166065	128166406
ENSE00003566878	128167095	128167164
ENSE00003571217	128176351	128176475
ENSE00003588138	128190329	128190444
ENSE00003605051	128180415	128180523
ENSE00003664412	128180721	128180814
ENSE00003691540	128169052	128169201
ENSE00003750254	128190688	128190862
ENSE00003760687	128191432	128191572

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.0974 / max 341.4775, expressed in 1821 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102673	56.9017	1820
102674	4.5773	1478
102671	0.8296	530
102679	0.5157	294
102672	0.1709	56
102675	0.0799	15
102676	0.0224	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.45	gold quality
cerebellar hemisphere	UBERON:0002245	98.30	gold quality
right ovary	UBERON:0002118	98.29	gold quality
left ovary	UBERON:0002119	98.29	gold quality
cerebellar cortex	UBERON:0002129	98.22	gold quality
tibial nerve	UBERON:0001323	98.10	gold quality
endocervix	UBERON:0000458	98.04	gold quality
body of pancreas	UBERON:0001150	97.96	gold quality
skin of leg	UBERON:0001511	97.96	gold quality
body of uterus	UBERON:0009853	97.95	gold quality
skin of abdomen	UBERON:0001416	97.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.84	gold quality
sural nerve	UBERON:0015488	97.81	gold quality
lower esophagus mucosa	UBERON:0035834	97.81	gold quality
right frontal lobe	UBERON:0002810	97.73	gold quality
apex of heart	UBERON:0002098	97.65	gold quality
lower esophagus	UBERON:0013473	97.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.51	gold quality
ectocervix	UBERON:0012249	97.50	gold quality
body of stomach	UBERON:0001161	97.35	gold quality
cerebellum	UBERON:0002037	97.35	gold quality
ganglionic eminence	UBERON:0004023	97.26	gold quality
left testis	UBERON:0004533	97.24	gold quality
right uterine tube	UBERON:0001302	97.23	gold quality
mucosa of stomach	UBERON:0001199	97.21	gold quality
popliteal artery	UBERON:0002250	97.18	gold quality
tibial artery	UBERON:0007610	97.18	gold quality
left uterine tube	UBERON:0001303	97.15	gold quality
minor salivary gland	UBERON:0001830	97.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting CIZ1, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-8055	97.62	66.09	1023

Literature-anchored findings (GeneRIF, showing 19)

• data indicate that Ciz1 is localized in the nucleus and is expressed in a wide range of tissues, especially the pancreas and the brain; formulated a consensus DNA sequence, ARYSR(0-2)YYAC, recognized by Ciz1 (PMID:12824700)
• Findings revealed the inherent role of Ciz1, a novel DNA binding and ER coactivator, in amplifying estrogenic responses and promoting breast cancer tumorigenesis. (PMID:17108141)
• conditional exclusion of exon 4 influences the spatial distribution of the Ciz1 protein within the nucleus, showing that CIZ1 alternative splicing could influence organized patterns of DNA replication (PMID:17508423)
• Ciz1 is a nuclear zinc finger protein interacting with p21, and is a DNA replication factor. The region of Ciz1 necessary for the interaction with ERH spans residues 531-644, encompassing its first zinc finger motif (PMID:18081865)
• An isoform of CIZ1 which lacks a glutamine-rich region, due to alternative splicing in exon 8, is upregulated in Alzheimer’s brains relative to the full-length CIZ1 protein. (PMID:18583151)
• alternatively spliced variant of Ciz1 is associated with cancer. (PMID:20831784)
• Mutations in CIZ1 may cause adult onset, primary cervical dystonia (PMID:22447717)
• Variant Ciz1 is a strong candidate for a cancer-specific single marker capable of identifying early-stage lung cancer. (PMID:23074256)
• This study suggested that No mutations in CIZ1 in twelve adult-onset primary cervical dystonia families. (PMID:23813719)
• CIZ1 may be involved in colon cancer progression by regulating cell proliferation, cell cycle, apoptosis and colony formation. (PMID:24126760)
• Our study demonstrated that CIZ1 played an oncogenic role in the progression of GBC and CIZ1 might be a promising target for the treatment of GBC (PMID:25427641)
• CIZ1 is a kinase sensor that promotes initiation of DNA replication at low kinase levels, when in a hypophosphorylated state that is permissive for cyclin-A-CDK2 interaction and delivery to licensed origins. (PMID:25736292)
• The results of this study showed CIZ1 will play a less important role in dystonia patient diagnosis than previously thought because variants of unclear significance are observed in approximately 1% of adult-onset sporadic dystonia patients in Germany. (PMID:25778706)
• CIZ1 activates YAP/TAZ signaling in human hepatocellular carcinoma cells. (PMID:26515335)
• our study demonstrated that CIZ1 is a positive regulator of YAP signaling, and CIZ1 might be a therapeutic target for hepatocellular carcinoma (PMID:26906552)
• data reveal that CIZ1 plays a major role in ensuring stable association of Xist RNA within the Xi territory. (PMID:28923964)
• High CIZ1 expression is associated with Hemangioma of the Tongue. (PMID:30456533)
• silencing of CIZ1 suppressed bladder cancer cell proliferation through inducing apoptosis and reducing cell cycle progression (PMID:31252164)
• Upregulation of lncRNA DANCR functions as an oncogenic role in non-small lung cancer by regulating miR-214-5p/CIZ1 axis. (PMID:32196604)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ciz1b	ENSDARG00000089461
danio_rerio	ciz1a	ENSDARG00000089781
mus_musculus	Ciz1	ENSMUSG00000039205
rattus_norvegicus	Ciz1	ENSRNOG00000013442
drosophila_melanogaster	Pep	FBGN0004401
drosophila_melanogaster	Ciz1	FBGN0027567

Protein

Protein identifiers

Cip1-interacting zinc finger protein — Q9ULV3 (reviewed: Q9ULV3)

Alternative names: CDKN1A-interacting zinc finger protein 1, Nuclear protein NP94, Zinc finger protein 356

All UniProt accessions (8): Q9ULV3, A0A0U1RQR2, A0A494C0L7, F5H2X7, F6VD24, F6WSM2, H0Y5D5, Q5SYW2

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the subcellular localization of CIP/WAF1.

Subunit / interactions. Interacts with CIP/WAF1.

Subcellular location. Nucleus.

Disease relevance. Defects in CIZ1 may be a cause of adult onset primary cervical dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Cervical dystonia or spasmodic torticollis, the most common form of focal dystonia, is characterized by involuntary contractions of the neck muscles, which produce abnormal posturing of the head upon the trunk.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9ULV3-1	1	yes
Q9ULV3-2	2, NP94B
Q9ULV3-3	3
Q9ULV3-4	4
Q9ULV3-5	5

RefSeq proteins (7): NP_001124487, NP_001124488, NP_001124489, NP_001124490, NP_001244904, NP_001244905, NP_036259 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000690	Matrin/U1-C_Znf_C2H2	Domain
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR013087	Znf_C2H2_type	Domain
IPR022755	Znf_C2H2_jaz	Domain
IPR026811	CIZ1	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR056345	Znf-C2H2_CIZ1	Domain

Pfam: PF12171, PF23330

UniProt features (66 total): sequence conflict 16, sequence variant 11, compositionally biased region 10, cross-link 9, modified residue 7, region of interest 5, splice variant 4, strand 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7X39	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULV3-F1	53.51	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (16): 209, 244, 350, 547, 567, 821, 838, 280, 340, 401, 549, 588, 680, 705, 830, 879

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 172 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, PAX4_01, TGCGCANK_UNKNOWN, GCM_GSPT1, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, AREB6_03, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_MAINTENANCE_OF_LOCATION, BLALOCK_ALZHEIMERS_DISEASE_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_MAINTENANCE_OF_PROTEIN_LOCALIZATION_IN_ORGANELLE, GCM_NUMA1, LAU_APOPTOSIS_CDKN2A_UP

GO Biological Process (3): positive regulation of DNA-templated DNA replication initiation (GO:0032298), maintenance of protein location in nucleus (GO:0051457), random inactivation of X chromosome (GO:0060816)

GO Molecular Function (5): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), cyclin binding (GO:0030332), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
DNA replication initiation	1
regulation of DNA-templated DNA replication initiation	1
positive regulation of DNA-templated DNA replication	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
dosage compensation by inactivation of X chromosome	1
transition metal ion binding	1
protein binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2023 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIZ1	CDKN1A	P38936	987
CIZ1	ANO3	Q9BYT9	787
CIZ1	THAP1	Q9NVV9	764
CIZ1	MCM3	P25205	736
CIZ1	GNAL	P38405	720
CIZ1	SPEN	Q96T58	668
CIZ1	TOR1A	O14656	656
CIZ1	PRRT2	Q7Z6L0	624
CIZ1	SGCE	O43556	606
CIZ1	TUBB4A	P04350	596
CIZ1	RBM15	Q96T37	594
CIZ1	ERH	P70659	592
CIZ1	MMP7	P09237	557
CIZ1	CDK2	P24941	557
CIZ1	HPCA	P32076	507

IntAct

51 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CCDC97	SF3B1	psi-mi:“MI:0914”(association)	0.730
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
SS18L2	SMARCA2	psi-mi:“MI:0914”(association)	0.570
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
SAFB2	DHPS	psi-mi:“MI:0914”(association)	0.530
DYNLL1	SHMT2	psi-mi:“MI:0914”(association)	0.510
DYNLL2	SHMT2	psi-mi:“MI:0914”(association)	0.510
SH3BP4	CIZ1	psi-mi:“MI:0915”(physical association)	0.510
SS18L2	ARID1A	psi-mi:“MI:0914”(association)	0.480
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
ERH	BCLAF3	psi-mi:“MI:0914”(association)	0.350
PTBP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
CCT8L2	DVL2	psi-mi:“MI:0914”(association)	0.350
CHTOP	PRMT5	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
TMED7	ATP9A	psi-mi:“MI:0914”(association)	0.350
TRIOBP	SKAP2	psi-mi:“MI:0914”(association)	0.350
L3MBTL2	MTA2	psi-mi:“MI:0914”(association)	0.350
ACP5	HSPA5	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Proximity Label-MS), CIZ1 (Proximity Label-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YWL9, A0A0J9YY54, A5D7L8, A6NJ88, D3YZV8, E9Q6E9, F1LWT0, O14686, O15069, P18583, P51843, P62521, P79386, Q0P6D6, Q13342, Q2EG98, Q3V3Q4, Q4R729, Q5HY64, Q5JRC9, Q5QGU6, Q6ITT4, Q6PDK2, Q70KF4, Q8CHD8, Q8N1P7, Q8N660, Q8N693, Q8N7U7, Q8NA70, Q8NDZ2, Q8TCU4, Q96JM3, Q99KW3, Q9BE18, Q9BG93, Q9BG94, Q9BG96, Q9BG97, Q9BXX2

Diamond homologs: E9PT37, O95758, P0DW16, P17225, P26599, Q00438, Q14966, Q29099, Q3UQS8, Q5T481, Q61464, Q66H20, Q8BHD7, Q8WN55, Q91Z31, Q9FGL9, Q9UKA9, Q9ULV3, Q9Z118, P43243, P43244, Q8K310

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	5	14.7×	2e-03
Epigenetic regulation of gene expression	6	10.7×	2e-03
Chromatin organization	5	10.2×	4e-03
Chromatin modifying enzymes	5	9.0×	7e-03
Metabolism of RNA	6	6.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	8	11.9×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	251
Likely benign	155
Benign	65

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1056169	NC_000009.11:g.(?129376729)(131016993_?)del	Pathogenic
2500126	NM_004408.4(DNM1):c.97C>T (p.Gln33Ter)	Pathogenic
968753	NM_004408.4(DNM1):c.128G>A (p.Gly43Asp)	Pathogenic
430565	NM_004408.4(DNM1):c.132G>T (p.Lys44Asn)	Likely pathogenic
4845385	NM_004408.4(DNM1):c.131A>G (p.Lys44Arg)	Likely pathogenic

SpliceAI

3110 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128163441:A:AG	acceptor_gain	1.0000
9:128163441:AGAAT:A	acceptor_loss	1.0000
9:128163442:G:GA	acceptor_gain	1.0000
9:128163442:GA:G	acceptor_gain	1.0000
9:128163442:GAA:G	acceptor_gain	1.0000
9:128163442:GAAT:G	acceptor_gain	1.0000
9:128166402:TATTT:T	acceptor_gain	1.0000
9:128166407:C:CC	acceptor_gain	1.0000
9:128166753:GCTCA:G	donor_loss	1.0000
9:128166754:CTCA:C	donor_loss	1.0000
9:128166755:TCACC:T	donor_loss	1.0000
9:128166756:CACCT:C	donor_loss	1.0000
9:128166757:A:C	donor_loss	1.0000
9:128166758:C:A	donor_loss	1.0000
9:128166877:ACACC:A	acceptor_loss	1.0000
9:128166878:CAC:C	acceptor_gain	1.0000
9:128166879:ACC:A	acceptor_loss	1.0000
9:128166880:CCTG:C	acceptor_loss	1.0000
9:128166881:C:CA	acceptor_loss	1.0000
9:128166882:T:A	acceptor_loss	1.0000
9:128169065:T:TA	donor_gain	1.0000
9:128169068:T:TA	donor_gain	1.0000
9:128169074:A:C	donor_gain	1.0000
9:128169092:T:TA	donor_gain	1.0000
9:128169197:TTCAG:T	acceptor_gain	1.0000
9:128169198:TCAG:T	acceptor_gain	1.0000
9:128169199:CAG:C	acceptor_gain	1.0000
9:128169199:CAGC:C	acceptor_gain	1.0000
9:128169200:AG:A	acceptor_gain	1.0000
9:128169201:GC:G	acceptor_loss	1.0000

AlphaMissense

5844 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128169492:A:G	C687R	1.000
9:128166834:G:C	C804W	0.999
9:128166836:A:G	C804R	0.999
9:128166843:G:C	C801W	0.999
9:128166845:A:G	C801R	0.999
9:128169442:G:C	H703Q	0.999
9:128169442:G:T	H703Q	0.999
9:128169452:A:G	F700S	0.999
9:128169481:G:C	C690W	0.999
9:128169482:C:T	C690Y	0.999
9:128169483:A:G	C690R	0.999
9:128169490:G:C	C687W	0.999
9:128169491:C:T	C687Y	0.999
9:128170039:C:G	R671P	0.999
9:128170040:G:T	R671S	0.999
9:128170076:A:G	C659R	0.999
9:128170083:G:C	C656W	0.999
9:128170084:C:G	C656S	0.999
9:128170085:A:G	C656R	0.999
9:128170085:A:T	C656S	0.999
9:128176471:A:G	F608S	0.999
9:128177601:A:G	C595R	0.999
9:128177729:A:G	I552T	0.999
9:128177729:A:T	I552N	0.999
9:128166763:A:G	L828P	0.998
9:128166835:C:T	C804Y	0.998
9:128166844:C:T	C801Y	0.998
9:128169141:C:G	A736P	0.998
9:128169143:T:A	D735V	0.998
9:128169152:A:C	I732S	0.998

dbSNP variants (sampled 300 via entrez): RS1000018120 (9:128172112 C>G,T), RS1000079023 (9:128165715 C>A,T), RS1000193021 (9:128166021 GC>G,GCC), RS1000215034 (9:128200582 A>C,G), RS1000248079 (9:128192097 C>A), RS1000380960 (9:128203908 C>T), RS1000389908 (9:128185394 T>C), RS1000415989 (9:128185737 G>A,C), RS1000437875 (9:128194564 C>A,G), RS1000716865 (9:128186836 A>G), RS1000749293 (9:128187159 C>T), RS1000857328 (9:128179947 C>G,T), RS1000913785 (9:128175865 T>C), RS1001059537 (9:128193410 C>A,G), RS1001186118 (9:128181926 T>C)

Disease associations

OMIM: gene MIM:611420 | disease phenotypes: MIM:616346, MIM:620352, MIM:614860

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia 23	Moderate	Unknown
inherited dystonia	Limited	Autosomal dominant

Mondo (8): dystonic disorder (MONDO:0003441), developmental and epileptic encephalopathy, 31A (MONDO:0014598), developmental and epileptic encephalopathy (MONDO:0100620), cerebellar ataxia (MONDO:0000437), stereotypic movement disorder (MONDO:0002265), developmental and epileptic encephalopathy, 31B (MONDO:0957248), dystonia 23 (MONDO:0013928), inherited dystonia (MONDO:0044807)

Orphanet (3): Lennox-Gastaut syndrome (Orphanet:2382), Rare ataxia (Orphanet:102002), Adult-onset cervical dystonia, DYT23 type (Orphanet:420492)

HPO phenotypes

17 total (18 of 17 shown, HPO-id order):

HPO	Term
HP:0000473	Torticollis
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001336	Myoclonus
HP:0001618	Dysphonia
HP:0002120	Cerebral cortical atrophy
HP:0002317	Unsteady gait
HP:0002346	Head tremor
HP:0002356	Writer’s cramp
HP:0002530	Axial dystonia
HP:0002883	Hyperventilation
HP:0004373	Focal dystonia
HP:0005115	Supraventricular arrhythmia
HP:0012179	Craniofacial dystonia
HP:0012893	Neck muscle hypertrophy
HP:0025269	Panic attack
HP:0200085	Limb tremor
HP:0001332	Dystonia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_65	Body mass index	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D020821	Dystonic Disorders	C10.228.662.300
D019956	Stereotypic Movement Disorder	F03.625.984

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
Cisplatin	decreases reaction, increases expression, decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Methotrexate	affects response to substance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
NCT01433757	PHASE1	COMPLETED	Ampicillin for DYT-1 Dystonia Motor Symptoms
NCT01698450	PHASE1	COMPLETED	Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
NCT02982304	PHASE1	UNKNOWN	Multi-Target Pallidal and Thalamic Deep Brain Stimulation for Hemi-Dystonia
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06554288	PHASE1	RECRUITING	Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT00004421	PHASE2/PHASE3	COMPLETED	Deep Brain Stimulation in Treating Patients With Dystonia
NCT00272246	PHASE2/PHASE3	UNKNOWN	Bilateral Internal Pallidum Stimulation in Primary Generalized Dystonia
NCT00608231	PHASE2/PHASE3	WITHDRAWN	Dexmedetomidine Effects on Microelectrode Recording in Deep Brain Stimulation
NCT04277247	PHASE2/PHASE3	UNKNOWN	Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson’s Disease
NCT02015039	PHASE1/PHASE2	COMPLETED	Pilot Trial of Botulinum Toxin and Occupational Therapy for Writer’s Cramp
NCT02911103	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Deep Brain Stimulation Surgery for Focal Hand Dystonia
NCT04727177	EARLY_PHASE1	UNKNOWN	Precision-targeted Transcranial Magnetic Stimulation in the Treatment of Primary Dystonia
NCT00006336	Not specified	COMPLETED	Sensory Training to Treat Focal Dystonia
NCT00017875	Not specified	COMPLETED	Transcranial Magnetic Stimulation (TMS) Studies of Dystonia
NCT00029601	Not specified	COMPLETED	Surround Inhibition in Patients With Dystonia
NCT00031369	Not specified	TERMINATED	Brain Anatomy in Dystonia
NCT00047957	Not specified	COMPLETED	Brain Inhibition of Muscle Movement in Normal Volunteers
NCT00050024	Not specified	COMPLETED	Transcranial Magnetic Stimulation and Electrical Stimulation of Nerves to Study Focal Dystonia
NCT00072956	Not specified	COMPLETED	The Physiology of Tricks
NCT00082615	Not specified	COMPLETED	Neurophysiological Markers in Patients With Craniofacial Dystonia and Their Relatives
NCT00102999	Not specified	COMPLETED	Brain Function in Focal Dystonia
NCT00285870	Not specified	COMPLETED	Quantification of Upper Extremity Hypertonia
NCT00355927	Not specified	UNKNOWN	Sedation During Microelectrode Recordings Before Deep Brain Stimulation for Movement Disorders.