ZMIZ1

Summary

ZMIZ1 (zinc finger MIZ-type containing 1, HGNC:16493) is a protein-coding gene on chromosome 10q22.3, encoding Zinc finger MIZ domain-containing protein 1 (Q9ULJ6). Acts as a transcriptional coactivator.

This gene encodes a member of the PIAS (protein inhibitor of activated STAT) family of proteins. The encoded protein regulates the activity of various transcription factors, including the androgen receptor, Smad3/4, and p53. The encoded protein may also play a role in sumoylation. A translocation between this locus on chromosome 10 and the protein tyrosine kinase ABL1 locus on chromosome 9 has been associated with acute lymphoblastic leukemia.

Source: NCBI Gene 57178 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 115
• Clinical variants (ClinVar): 802 total — 19 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 61
• MANE Select transcript: NM_020338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16493
Approved symbol	ZMIZ1
Name	zinc finger MIZ-type containing 1
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	RP11-519K18.1, KIAA1224, FLJ13541, hZIMP10, Zimp10, MIZ
Ensembl gene	ENSG00000108175
Ensembl biotype	protein_coding
OMIM	607159
Entrez	57178

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000334512, ENST00000472035, ENST00000478357, ENST00000880200, ENST00000880201, ENST00000880202, ENST00000880203, ENST00000880204, ENST00000880205, ENST00000928253, ENST00000928254, ENST00000928255, ENST00000928256, ENST00000956708, ENST00000956709

RefSeq mRNA: 1 — MANE Select: NM_020338 NM_020338

CCDS: CCDS7357

Canonical transcript exons

ENST00000334512 — 25 exons

Exon	Start	End
ENSE00000986214	79297613	79297690
ENSE00000986215	79298406	79298580
ENSE00000986216	79299050	79299191
ENSE00000986222	79304015	79304175
ENSE00000986225	79305533	79305601
ENSE00000986226	79306100	79306344
ENSE00000986227	79307405	79307571
ENSE00000986228	79310924	79311184
ENSE00001249873	79296471	79296653
ENSE00001249890	79293381	79293653
ENSE00001338895	79216169	79216274
ENSE00001338902	79162053	79162133
ENSE00001457591	79139682	79139777
ENSE00001457593	79118915	79119024
ENSE00001457594	79068966	79069270
ENSE00001638843	79305164	79305231
ENSE00001656155	79302107	79302212
ENSE00001673417	79300732	79300942
ENSE00001763408	79208336	79208449
ENSE00001937263	79312642	79316519
ENSE00002270426	79201584	79201692
ENSE00003477099	79277181	79277325
ENSE00003556418	79289775	79289889
ENSE00003604990	79290959	79291176
ENSE00003662428	79292158	79292356

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.6665 / max 1035.8752, expressed in 1822 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105703	44.3709	1812
105702	8.0160	1648
105729	2.0094	577
105727	1.6861	553
105775	1.2239	257
105744	0.9468	537
105704	0.8888	615
105711	0.7577	493
105743	0.4872	265
105774	0.3245	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.86	gold quality
tibia	UBERON:0000979	98.57	gold quality
seminal vesicle	UBERON:0000998	98.48	gold quality
inferior olivary complex	UBERON:0002127	98.15	gold quality
ganglionic eminence	UBERON:0004023	98.14	gold quality
endothelial cell	CL:0000115	97.92	gold quality
cortical plate	UBERON:0005343	97.86	gold quality
synovial joint	UBERON:0002217	97.68	gold quality
urethra	UBERON:0000057	97.66	gold quality
mammalian vulva	UBERON:0000997	97.60	gold quality
hair follicle	UBERON:0002073	97.55	gold quality
caput epididymis	UBERON:0004358	97.50	gold quality
embryo	UBERON:0000922	97.44	gold quality
corpus epididymis	UBERON:0004359	97.41	gold quality
decidua	UBERON:0002450	97.39	gold quality
parotid gland	UBERON:0001831	97.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.38	gold quality
cartilage tissue	UBERON:0002418	97.30	gold quality
epithelium of mammary gland	UBERON:0003244	97.26	gold quality
visceral pleura	UBERON:0002401	97.23	gold quality
mammary duct	UBERON:0001765	97.22	gold quality
tongue squamous epithelium	UBERON:0006919	97.18	gold quality
ventricular zone	UBERON:0003053	97.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.17	gold quality
cervix squamous epithelium	UBERON:0006922	97.13	gold quality
cauda epididymis	UBERON:0004360	97.12	gold quality
epithelial cell of pancreas	CL:0000083	97.02	gold quality
lower lobe of lung	UBERON:0008949	97.00	gold quality
middle temporal gyrus	UBERON:0002771	96.98	gold quality
adult organism	UBERON:0007023	96.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.35

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
MYC	Activation
RHOA	Activation

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

237 targeting ZMIZ1, 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-4455	100.00	65.48	1587
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
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-6748-5P	100.00	65.81	1057
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068

Literature-anchored findings (GeneRIF, showing 30)

• First line of evidence demonstrates a physiological role for endogenous Zimp10 in regulating Smad3/4-mediated transcription. (PMID:16777850)
• (RAI17) was found to be upregulated in WT-Add1 vs MUT-Add1 overexpressing cells, possibly representing a key molecule/axis for the functional Add1-induced effect (PMID:17512505)
• Expression of exogenous hZimp10 enhances the transcriptional activity of p53 and knockdown of endogenous hZimp10 reduces the transcriptional activity of p53. (PMID:17584785)
• provides evidence to demonstrate a crucial role for Zimp10 in vasculogenesis (PMID:17967885)
• Fusion of ZMIZ1 to ABL1 is associated with a B-cell acute lymphoblastic leukemia with a t(9;10)(q34;q22.3) translocation (PMID:18007576)
• ZMIZ1 and activated NOTCH1 are coexpressed in a subset of human T-ALL patients and cell lines. (PMID:23161489)
• ZMIZ1 is overexpressed in a significant percentage of human breast, ovarian, and colon cancers in addition to human squamous cell carcinomas, suggesting that ZMIZ1 may play a broader role in epithelial cancers. (PMID:23426136)
• ZMIZ1 is a susceptibility gene for vitiligo in Chinese population. (PMID:24667117)
• This case represents the first constitutional balanced translocation disrupting and fusing both MIZ-type containing and proline-rich 12 and provides clues for the potential function and effects of these in the central nervous system. (PMID:26163108)
• the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. (PMID:26403403)
• Targeting the NOTCH1-ZMIZ1 interaction might combat leukemic growth. (PMID:26522984)
• At the ZMIZ1 locus, we show that perturbation of ZMIZ1 expression in human islets and beta-cells influences exocytosis and insulin secretion, highlighting a novel role for ZMIZ1 in the maintenance of glucose homeostasis. (PMID:26624892)
• we have identified a molecular phenotype of MS defined by expression of the MS risk gene ZMIZ1 in blood, and by other genes, especially transcription factors. ZMIZ1 expression is affected by, and interacts with, the environmental risk factors EBV and Vitamin D. (PMID:28063629)
• In a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in Chinese women, analysis provided evidence of a significant (P<5 x 10(-8)) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. (PMID:28447608)
• rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to Inflammatory Bowel Disease in Han-Chinese patients. (PMID:28456797)
• data supports a role for regulation of these genes in mononuclear phagocytic cells by vitamin D as contributing to autoimmunity (PMID:30285234)
• ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder (PMID:30639322)
• ZMIZ1 as a prognostic marker in cancer. (PMID:31373686)
• circular RNA ZMIZ1 is upregulated in prostate cancer cells and promotes cell proliferation (PMID:31686520)
• Autosomal dominant inheritance in a recently described ZMIZ1-related neurodevelopmental disorder: Case report of siblings and an affected parent. (PMID:31833199)
• Long non-coding RNA ZMIZ1-AS1 promotes osteosarcoma progression by stabilization of ZMIZ1. (PMID:34508303)
• Compound Heterozygote of Point Mutation and Chromosomal Microdeletion Involving OTUD6B Coinciding with ZMIZ1 Variant in Syndromic Intellectual Disability. (PMID:34680978)
• Zmiz1 is required for mature beta-cell function and mass expansion upon high fat feeding. (PMID:36307047)
• Clinical report and genetic analysis of a novel variant in ZMIZ1 causing neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies in a Chinese family. (PMID:38117436)
• Decreased ZMIZ1 suppresses melanogenesis in vitiligo by regulating mTOR/AKT/GSK-3beta-mediated glucose uptake. (PMID:38117454)
• ZMIZ1 Regulates Proliferation, Autophagy and Apoptosis of Colon Cancer Cells by Mediating Ubiquitin-Proteasome Degradation of SIRT1. (PMID:38214831)
• Knockdown of circZMIZ1 enhances the anti-tumor activity of CD8[+] T cells to alleviate hepatocellular carcinoma. (PMID:38332346)
• Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function. (PMID:38718095)
• Targeting the ZMIZ1-Notch1 signaling axis for the treatment of tongue squamous cell carcinoma. (PMID:38866828)
• Association of LPP and ZMIZ1 Gene Polymorphism with Celiac Disease in Subjects from Punjab, Pakistan. (PMID:39062631)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zmiz1a	ENSDARG00000074502
danio_rerio	zmiz1b	ENSDARG00000102279
mus_musculus	Zmiz1	ENSMUSG00000007817
rattus_norvegicus	Zmiz1	ENSRNOG00000010488
drosophila_melanogaster	tna	FBGN0026160
caenorhabditis_elegans		WBGENE00011259

Paralogs (5): PIAS1 (ENSG00000033800), PIAS2 (ENSG00000078043), PIAS4 (ENSG00000105229), ZMIZ2 (ENSG00000122515), PIAS3 (ENSG00000131788)

Protein

Protein identifiers

Zinc finger MIZ domain-containing protein 1 — Q9ULJ6 (reviewed: Q9ULJ6)

Alternative names: PIAS-like protein Zimp10, Retinoic acid-induced protein 17

All UniProt accessions (1): Q9ULJ6

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional coactivator. Increases ligand-dependent transcriptional activity of AR and promotes AR sumoylation. The stimulation of AR activity is dependent upon sumoylation. Also functions as a transcriptional coactivator in the TGF-beta signaling pathway by increasing the activity of the SMAD3/SMAD4 transcriptional complex. Involved in transcriptional activation of a subset of NOTCH1 target genes including MYC. Involved in thymocyte and T cell development. Involved in the regulation of postmitotic positioning of pyramidal neurons in the developing cerebral cortex.

Subunit / interactions. Interacts with AR, but not with ESR1, NR3C1, PGR, THRB nor VDR. Interacts with NOTCH1 and RBPJ. Interacts with SMARCA4. Interacts (via SP-RING-type domain) with SMAD3 and SMAD4 (via MH2 domain).

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm.

Tissue specificity. Expressed most abundantly in ovary and, at lower levels, in prostate, spleen and testis. Weak expression, if any, in thymus, small intestine, colon and peripheral blood leukocytes.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA) [MIM:618659] An autosomal dominant disorder characterized by intellectual disability, developmental delay, poor language acquisition, behavioral abnormalities, growth failure, feeding difficulties, microcephaly, facial dysmorphism, and mild skeletal anomalies of the hands and feet. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The SP-RING-type domain mediates interaction with SMAD3 and SMAD4. The C-terminal proline-rich domain possesses a significant intrinsic transcriptional activity. This activity is inhibited by the N-terminus in the full-length protein.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULJ6-1	1	yes
Q9ULJ6-3	3

RefSeq proteins (1): NP_065071* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004181	Znf_MIZ	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR040797	ZMIZ1_N	Domain
IPR057847	ZMIZ1/ZMIZ2_GBD-like	Domain

Pfam: PF02891, PF18028, PF25527

UniProt features (40 total): compositionally biased region 10, sequence variant 7, helix 7, region of interest 5, binding site 4, cross-link 3, chain 1, zinc finger region 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5AIZ	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULJ6-F1	58.36	0.29

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 (4): 758; 760; 781; 784

Post-translational modifications (3): 91, 834, 843

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 592 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_ACTIVATION, FXR_IR1_Q6, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_CELLULAR_RESPONSE_TO_LIPID, GCANCTGNY_MYOD_Q6, MODULE_45, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_GROWTH, MODULE_493, GENTILE_RESPONSE_CLUSTER_D3

GO Biological Process (17): vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), heart morphogenesis (GO:0003007), regulation of transcription by RNA polymerase II (GO:0006357), transforming growth factor beta receptor signaling pathway (GO:0007179), vitellogenesis (GO:0007296), protein sumoylation (GO:0016925), pyramidal neuron migration to cerebral cortex (GO:0021852), androgen receptor signaling pathway (GO:0030521), positive regulation of T cell differentiation (GO:0045582), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), developmental growth (GO:0048589), artery morphogenesis (GO:0048844), SMAD protein signal transduction (GO:0060395), cellular senescence (GO:0090398)

GO Molecular Function (5): transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), SMAD binding (GO:0046332), SUMO ligase activity (GO:0061665), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
blood vessel morphogenesis	2
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
cell differentiation	1
chordate embryonic development	1
heart development	1
animal organ morphogenesis	1
regulation of DNA-templated transcription	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cytoplasm organization	1
female gamete generation	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
cerebral cortex radial glia-guided migration	1
pyramidal neuron development	1
radial glia-guided pyramidal neuron migration	1
nuclear receptor-mediated steroid hormone signaling pathway	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
positive regulation of signal transduction	1
regulation of transcription by RNA polymerase II	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
developmental process	1
growth	1
artery development	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
intracellular signaling cassette	1
cellular process	1
cellular response to stress	1
transcription coregulator activity	1
transition metal ion binding	1
protein binding	1

Protein interactions and networks

STRING

1686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZMIZ1	AR	P10275	726
ZMIZ1	SUMO1	P55856	635
ZMIZ1	SUMO2	P55855	552
ZMIZ1	SMARCE1	Q969G3	520
ZMIZ1	YDJC	A8MPS7	514
ZMIZ1	RBPJ	Q06330	512
ZMIZ1	MYC	P01106	502
ZMIZ1	NOTCH1	P46531	483
ZMIZ1	RCSD1	Q6JBY9	477
ZMIZ1	PIAS2	O75928	465
ZMIZ1	KLHL42	Q9P2K6	447
ZMIZ1	TLE3	Q04726	439
ZMIZ1	ANKRD16	Q6P6B7	431
ZMIZ1	CNTNAP2	Q9UHC6	420
ZMIZ1	CNTN2	P78432	410

IntAct

22 interactions, top by confidence:

A	B	Type	Score
Dlg4	ZMIZ1	psi-mi:“MI:0407”(direct interaction)	0.440
TBC1D4	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.370
CNTNAP2	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.370
CACHD1	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.370
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
ETV4	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TBR1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.000
ZMIZ1	polA	psi-mi:“MI:0915”(physical association)	0.000
gpmI	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.000
ZMIZ1		psi-mi:“MI:0915”(physical association)	0.000
ZMIZ1	flgH2	psi-mi:“MI:0915”(physical association)	0.000
ZMIZ1	gptB	psi-mi:“MI:0915”(physical association)	0.000
tnpA	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.000
ZMIZ1	glsA1	psi-mi:“MI:0915”(physical association)	0.000
chbG	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (65): SETD4 (Co-fractionation), ZMIZ1 (Affinity Capture-MS), MAML1 (Affinity Capture-MS), RBPJ (Affinity Capture-MS), NOTCH1 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), SATB1 (Affinity Capture-MS), NFATC3 (Affinity Capture-MS), CTNNB1 (Affinity Capture-MS), ZEB1 (Affinity Capture-MS), CCR7 (Affinity Capture-MS), BRCA1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), TCF7 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS)

ESM2 similar proteins: A7EYK3, A7SEP9, A8NYM5, A8XW44, B0JYS7, B7Q2M2, C0NN85, C7YRT4, D3ZCL3, D5GDH4, E0VI98, E1C6F0, E2RGI3, E3X5D6, F6TFD9, F7ARS3, P09234, P33240, P90815, Q03369, Q15637, Q16IW3, Q1K7T5, Q1RLC9, Q298E0, Q32PA0, Q4WQM6, Q562A2, Q5BBX9, Q5RDA3, Q5U231, Q62241, Q64213, Q6GPM1, Q6P1E1, Q6PCR6, Q7PXU6, Q8BIQ5, Q8C7E9, Q8CIE2

Diamond homologs: A0A0A7EPL0, F4JYG0, O94451, Q04195, Q6P1E1, Q8CIE2, Q8N2W9, Q8NF64, Q94361, Q9JM05, Q9ULJ6, F1R4C4, O54714, O70260, O75925, O75928, O88907, Q12216, Q680Q4, Q6ASW7, Q6AZ28, Q6L4L4, Q8C5D8, Q9Y6X2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ZMIZ1	“up-regulates activity”	AR	binding
ZMIZ1	“up-regulates activity”	NOTCH1	binding
NOTCH1	“up-regulates activity”	ZMIZ1	binding
ZMIZ1	up-regulates	Chromatine_condensation
ZMIZ1	“up-regulates quantity by expression”	MYC	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	29
Uncertain significance	362
Likely benign	272
Benign	58

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071297	NM_020338.4(ZMIZ1):c.783del (p.Ala262fs)	Pathogenic
1071555	NM_020338.4(ZMIZ1):c.816del (p.Pro273fs)	Pathogenic
2446496	NM_020338.4(ZMIZ1):c.2038C>T (p.Gln680Ter)	Pathogenic
2692559	NM_020338.4(ZMIZ1):c.1557dup (p.Met520fs)	Pathogenic
3193716	NM_020338.4(ZMIZ1):c.2194G>T (p.Glu732Ter)	Pathogenic
3251935	NM_020338.4(ZMIZ1):c.2615_2628del (p.Tyr872fs)	Pathogenic
3254944	NM_020338.4(ZMIZ1):c.1792C>T (p.Gln598Ter)	Pathogenic
3361817	NM_020338.4(ZMIZ1):c.2218_2219del (p.Leu740fs)	Pathogenic
3572496	NM_020338.4(ZMIZ1):c.320del (p.Leu107fs)	Pathogenic
3780968	NM_020338.4(ZMIZ1):c.881C>T (p.Thr294Ile)	Pathogenic
3819528	NM_020338.4(ZMIZ1):c.40C>T (p.Arg14Ter)	Pathogenic
3907761	NM_020338.4(ZMIZ1):c.2614del (p.Tyr872fs)	Pathogenic
4074993	NM_020338.4(ZMIZ1):c.857_872del (p.Ala286fs)	Pathogenic
4082022	NM_020338.4(ZMIZ1):c.1538del (p.Pro513fs)	Pathogenic
548962	NM_020338.4(ZMIZ1):c.2758dup (p.Gln920fs)	Pathogenic
694588	NM_020338.4(ZMIZ1):c.899C>T (p.Thr300Met)	Pathogenic
984582	NM_020338.4(ZMIZ1):c.253C>T (p.Arg85Ter)	Pathogenic
985126	NM_020338.4(ZMIZ1):c.1372C>T (p.Gln458Ter)	Pathogenic
996613	NM_020338.4(ZMIZ1):c.887C>T (p.Thr296Ile)	Pathogenic
1205213	NM_020338.4(ZMIZ1):c.425+1G>A	Likely pathogenic
1285409	NM_020338.4(ZMIZ1):c.1131dup (p.Phe378fs)	Likely pathogenic
1334448	NM_020338.4(ZMIZ1):c.1030_1031dup (p.Ser345fs)	Likely pathogenic
1478592	NM_020338.4(ZMIZ1):c.845_862dup (p.Ala282_Ala287dup)	Likely pathogenic
1480952	NM_020338.4(ZMIZ1):c.1230+2T>C	Likely pathogenic
2136139	NM_020338.4(ZMIZ1):c.3150del (p.Asp1051fs)	Likely pathogenic
2499825	NM_020338.4(ZMIZ1):c.2710G>A (p.Gly904Arg)	Likely pathogenic
2503420	NM_020338.4(ZMIZ1):c.328C>T (p.Arg110Ter)	Likely pathogenic
2572573	NM_020338.4(ZMIZ1):c.969_970del (p.Gln324fs)	Likely pathogenic
2576011	NM_020338.4(ZMIZ1):c.1566del (p.Ser524fs)	Likely pathogenic
2577982	NM_020338.4(ZMIZ1):c.1489dup (p.Arg497fs)	Likely pathogenic

SpliceAI

5279 predictions. Top by Δscore:

Variant	Effect	Δscore
10:79118909:CCATA:C	acceptor_loss	1.0000
10:79118910:CATA:C	acceptor_loss	1.0000
10:79118912:TA:T	acceptor_loss	1.0000
10:79118913:A:AT	acceptor_loss	1.0000
10:79119021:GCAG:G	donor_gain	1.0000
10:79119022:CAGG:C	donor_loss	1.0000
10:79119023:AGGT:A	donor_loss	1.0000
10:79119024:GGTA:G	donor_loss	1.0000
10:79119025:G:C	donor_loss	1.0000
10:79119026:T:A	donor_loss	1.0000
10:79201579:CGCA:C	acceptor_loss	1.0000
10:79201580:GCAG:G	acceptor_loss	1.0000
10:79201582:A:AC	acceptor_loss	1.0000
10:79201582:A:AG	acceptor_gain	1.0000
10:79201582:AG:A	acceptor_gain	1.0000
10:79201582:AGGCT:A	acceptor_gain	1.0000
10:79201583:G:GC	acceptor_gain	1.0000
10:79201583:GG:G	acceptor_gain	1.0000
10:79201583:GGC:G	acceptor_gain	1.0000
10:79201583:GGCT:G	acceptor_gain	1.0000
10:79201583:GGCTG:G	acceptor_gain	1.0000
10:79201689:GCAG:G	donor_gain	1.0000
10:79201691:AGGT:A	donor_loss	1.0000
10:79201691:AGGTG:A	donor_gain	1.0000
10:79201693:G:GA	donor_loss	1.0000
10:79208333:C:G	acceptor_gain	1.0000
10:79208334:A:AG	acceptor_gain	1.0000
10:79208335:G:GA	acceptor_gain	1.0000
10:79208335:GC:G	acceptor_gain	1.0000
10:79208335:GCA:G	acceptor_gain	1.0000

AlphaMissense

7067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:79201672:C:G	R14G	1.000
10:79201673:G:C	R14P	1.000
10:79201676:T:A	L15Q	1.000
10:79201676:T:C	L15P	1.000
10:79201676:T:G	L15R	1.000
10:79201681:T:C	C17R	1.000
10:79201685:T:A	I18N	1.000
10:79208340:T:C	L22S	1.000
10:79208357:T:C	F28L	1.000
10:79208358:T:C	F28S	1.000
10:79208358:T:G	F28C	1.000
10:79208359:C:A	F28L	1.000
10:79208359:C:G	F28L	1.000
10:79208369:G:C	A32P	1.000
10:79208370:C:A	A32D	1.000
10:79208375:G:A	E34K	1.000
10:79208379:T:A	L35Q	1.000
10:79208379:T:C	L35P	1.000
10:79208379:T:G	L35R	1.000
10:79208382:T:C	L36P	1.000
10:79208387:T:A	W38R	1.000
10:79208387:T:C	W38R	1.000
10:79208388:G:C	W38S	1.000
10:79208389:G:C	W38C	1.000
10:79208389:G:T	W38C	1.000
10:79208390:T:C	C39R	1.000
10:79208391:G:A	C39Y	1.000
10:79208392:C:G	C39W	1.000
10:79208406:C:A	A44D	1.000
10:79208408:T:C	F45L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001186 (10:79196558 C>A,T), RS1000032175 (10:79274602 C>T), RS1000038447 (10:79233239 G>A), RS1000042508 (10:79077048 A>G), RS1000044280 (10:79194834 C>T), RS1000057814 (10:79200228 C>T), RS1000058571 (10:79242800 C>T), RS1000061933 (10:79209127 T>C), RS1000097784 (10:79184068 G>A), RS1000097999 (10:79282157 A>C,G), RS1000102542 (10:79239628 G>A,T), RS1000115830 (10:79202988 C>T), RS1000120982 (10:79299301 C>T), RS1000127896 (10:79114560 G>A), RS1000145951 (10:79082953 C>T)

Disease associations

OMIM: gene MIM:607159 | disease phenotypes: MIM:618659, MIM:618660

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies	Strong	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (6): neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (MONDO:0032855), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), hemolytic anemia due to glutathione reductase deficiency (MONDO:0019531), syndromic intellectual disability (MONDO:0000508)

Orphanet (3): Hemolytic anemia due to glutathione reductase deficiency (Orphanet:90030), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000483	Astigmatism
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000582	Upslanted palpebral fissure
HP:0000589	Coloboma
HP:0000646	Amblyopia
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001156	Brachydactyly
HP:0001182	Tapered finger
HP:0001249	Intellectual disability

GWAS associations

115 associations (top):

Study	Trait	p-value
GCST000424_14	Multiple sclerosis	2.000000e-06
GCST000531_4	Inflammatory bowel disease (early onset)	6.000000e-09
GCST000612_25	Celiac disease	9.000000e-10
GCST000678_9	Breast cancer	4.000000e-09
GCST000692_3	Vitiligo	8.000000e-07
GCST000879_3	Crohn’s disease	1.000000e-30
GCST001198_41	Multiple sclerosis	6.000000e-09
GCST001341_11	Multiple sclerosis	4.000000e-07
GCST001473_1	Crohn’s disease and psoriasis	7.000000e-14
GCST001877_56	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	5.000000e-06
GCST001937_4	Breast cancer	7.000000e-22
GCST001956_38	Height	2.000000e-09
GCST002352_59	Type 2 diabetes	2.000000e-10
GCST002408_8	Response to methotrexate in juvenile idiopathic arthritis	1.000000e-06
GCST002408_9	Response to methotrexate in juvenile idiopathic arthritis	7.000000e-06
GCST002454_5	Colorectal cancer	2.000000e-08
GCST002647_37	Height	5.000000e-14
GCST002702_88	Height	8.000000e-08
GCST002930_17	Cobalt levels	7.000000e-06
GCST003097_21	Pediatric autoimmune diseases	1.000000e-08
GCST003268_14	Psoriasis vulgaris	1.000000e-07
GCST003400_49	Type 2 diabetes	3.000000e-08
GCST004131_86	Inflammatory bowel disease	4.000000e-12
GCST004132_102	Crohn’s disease	9.000000e-15
GCST004562_142	Waist circumference adjusted for body mass index	9.000000e-09
GCST004562_241	Waist circumference adjusted for body mass index	2.000000e-06
GCST004562_37	Waist circumference adjusted for body mass index	6.000000e-09
GCST004563_119	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-07
GCST004563_123	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	5.000000e-08
GCST004564_179	Waist circumference adjusted for BMI in active individuals	3.000000e-07

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0007987	granulocyte count
EFO:0007984	platelet component distribution width
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0003924	hair color
EFO:0009779	tri-iodothyronine/thyroxine ratio measurement
EFO:0009924	Drugs used in diabetes use measurement
EFO:0004531	urate measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004462	PR interval
EFO:0004644	TPE interval measurement
EFO:0004327	electrocardiography
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs117484357	ZMIZ1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects expression, affects methylation	6
methylmercuric chloride	increases expression, affects cotreatment	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	increases methylation, decreases methylation, decreases expression, affects cotreatment	2
Arsenic	affects methylation, increases abundance, increases expression	2
Cisplatin	decreases expression	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Valproic Acid	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
trichostatin A	decreases expression	1
2-butenal	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	affects methylation	1
versicolorin A	decreases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6NC	COG-LL-394h	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder