ZMAT3

Summary

ZMAT3 (zinc finger matrin-type 3, HGNC:29983) is a protein-coding gene on chromosome 3q26.32, encoding Zinc finger matrin-type protein 3 (Q9HA38). Acts as a bona fide target gene of p53/TP53.

This gene encodes a protein containing three zinc finger domains and a nuclear localization signal. The mRNA and the protein of this gene are upregulated by wildtype p53 and overexpression of this gene inhibits tumor cell growth, suggesting that this gene may have a role in the p53-dependent growth regulatory pathway. Alternative splicing of this gene results in two transcript variants encoding two isoforms differing in only one amino acid.

Source: NCBI Gene 64393 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 47 total
• GTEx eGene: eQTL in 19 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.76 (unconstrained)
• MANE Select transcript: NM_022470

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29983
Approved symbol	ZMAT3
Name	zinc finger matrin-type 3
Location	3q26.32
Locus type	gene with protein product
Status	Approved
Aliases	WIG1, MGC10613, FLJ12296, WIG-1, PAG608
Ensembl gene	ENSG00000172667
Ensembl biotype	protein_coding
OMIM	606452
Entrez	64393

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000311417

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 4: 1

ENST00000311417, ENST00000414084, ENST00000432729, ENST00000652290, ENST00000867369, ENST00000867370, ENST00000867371, ENST00000867372, ENST00000867373, ENST00000931263, ENST00000992683, ENST00000992684, ENST00001080681, ENST00001116476, ENST00001144612

RefSeq mRNA: 8 — MANE Select: NM_022470 NM_001375824, NM_001375825, NM_001375826, NM_001375827, NM_001375828, NM_001375829, NM_022470, NM_152240

CCDS: CCDS3224, CCDS46962

Canonical transcript exons

ENST00000311417 — 6 exons

Exon	Start	End
ENSE00001206616	179027423	179027523
ENSE00001206618	179027646	179027812
ENSE00001206621	179030880	179030999
ENSE00001206631	179017223	179025228
ENSE00001206636	179067483	179067809
ENSE00003843915	179071595	179071809

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.2319 / max 225.5099, expressed in 1814 samples.

Highest expression (Bgee): postcentral gyrus, Brodmann (1909) area 23, parietal lobe, entorhinal cortex, substantia nigra pars compacta.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ZMAT3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	4.7e-13	-0.20	3:179032427:G:A
Brain Hypothalamus	eqtl	6.5e-06	+0.23	3:179004026:A:G
Spleen	eqtl	4.3e-05	+0.31	3:179035359:C:T
Esophagus Mucosa	eqtl	1.8e-04	+0.19	3:178946267:A:AT
Adrenal Gland	eqtl	1.3e-03	-0.60	3:178956184:G:T
Artery Tibial	eqtl	4.8e-03	+0.37	3:179485530:G:A
Cells Cultured fibroblasts	eqtl	5.4e-03	+0.09	3:179034990:G:A
Pituitary	eqtl	5.9e-03	-0.26	3:178963453:C:T
Lung	sqtl	9.3e-03	+0.32	3:179520980:A:C
Brain Nucleus accumbens basal ganglia	eqtl	1.5e-02	-0.39	3:179017424:T:C
Brain Anterior cingulate cortex BA24	eqtl	1.6e-02	+0.60	3:179735104:C:T
Cells EBV-transformed lymphocytes	eqtl	1.6e-02	-0.14	3:178976298:T:G
Artery Tibial	sqtl	1.8e-02	+0.28	3:179680439:G:A
Muscle Skeletal	eqtl	2.2e-02	-0.12	3:179013232:G:A
Brain Putamen basal ganglia	eqtl	2.4e-02	-0.18	3:179944735:A:T
Pituitary	sqtl	2.6e-02	-2.02	3:179248402:G:A
Brain Frontal Cortex BA9	eqtl	2.7e-02	-0.68	3:178274944:T:C
Brain Hippocampus	eqtl	2.7e-02	-0.18	3:178657400:G:A
Skin Sun Exposed Lower leg	eqtl	3.2e-02	+0.11	3:179035359:C:T
Thyroid	eqtl	3.2e-02	-0.18	3:179249918:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
45709	19.7864	1795
45708	10.4612	1544
45710	1.1312	753
45711	0.8232	514
45712	0.7065	400
45707	0.2424	124
45713	0.0809	16

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
postcentral gyrus	UBERON:0002581	96.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.37	gold quality
parietal lobe	UBERON:0001872	96.05	gold quality
entorhinal cortex	UBERON:0002728	95.12	gold quality
substantia nigra pars compacta	UBERON:0001965	95.10	gold quality
cauda epididymis	UBERON:0004360	95.03	gold quality
medial globus pallidus	UBERON:0002477	94.95	gold quality
superior frontal gyrus	UBERON:0002661	94.42	gold quality
globus pallidus	UBERON:0001875	94.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.09	gold quality
middle temporal gyrus	UBERON:0002771	93.85	gold quality
superior vestibular nucleus	UBERON:0007227	93.47	gold quality
germinal epithelium of ovary	UBERON:0001304	92.62	gold quality
ventral tegmental area	UBERON:0002691	92.54	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.37	gold quality
inferior vagus X ganglion	UBERON:0005363	92.30	gold quality
pons	UBERON:0000988	91.68	gold quality
lateral globus pallidus	UBERON:0002476	91.30	gold quality
occipital lobe	UBERON:0002021	91.01	gold quality
dorsal root ganglion	UBERON:0000044	90.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.72	gold quality
visceral pleura	UBERON:0002401	90.66	gold quality
trigeminal ganglion	UBERON:0001675	90.51	gold quality
stromal cell of endometrium	CL:0002255	90.39	gold quality
primary visual cortex	UBERON:0002436	90.27	gold quality
nipple	UBERON:0002030	90.16	gold quality
mammary duct	UBERON:0001765	90.04	gold quality
parietal pleura	UBERON:0002400	89.91	gold quality
caput epididymis	UBERON:0004358	89.83	gold quality
subthalamic nucleus	UBERON:0001906	89.67	gold quality
pleura	UBERON:0000977	89.58	gold quality
corpus epididymis	UBERON:0004359	89.50	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.19	gold quality
tibia	UBERON:0000979	88.91	gold quality
epithelium of mammary gland	UBERON:0003244	88.40	gold quality
temporal lobe	UBERON:0001871	88.20	gold quality
skin of hip	UBERON:0001554	88.10	gold quality
renal medulla	UBERON:0000362	87.42	gold quality
saphenous vein	UBERON:0007318	87.31	gold quality
pigmented layer of retina	UBERON:0001782	87.18	gold quality
superficial temporal artery	UBERON:0001614	87.13	gold quality
medulla oblongata	UBERON:0001896	86.92	gold quality
cerebellar vermis	UBERON:0004720	86.90	gold quality
orbitofrontal cortex	UBERON:0004167	86.65	gold quality
seminal vesicle	UBERON:0000998	86.55	gold quality
cerebral cortex	UBERON:0000956	86.33	gold quality
frontal cortex	UBERON:0001870	86.21	gold quality
prefrontal cortex	UBERON:0000451	86.07	gold quality
Ammon’s horn	UBERON:0001954	86.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.85	gold quality
telencephalon	UBERON:0001893	85.82	gold quality
epithelium of nasopharynx	UBERON:0001951	85.67	gold quality
neocortex	UBERON:0001950	85.61	gold quality
midbrain	UBERON:0001891	85.01	gold quality
adult organism	UBERON:0007023	84.97	gold quality
lower lobe of lung	UBERON:0008949	84.96	gold quality
esophagus squamous epithelium	UBERON:0006920	84.93	gold quality
endothelial cell	CL:0000115	84.82	gold quality
forebrain	UBERON:0001890	84.78	gold quality
thoracic mammary gland	UBERON:0005200	84.64	gold quality
mammary gland	UBERON:0001911	84.54	gold quality
nucleus accumbens	UBERON:0001882	84.38	gold quality
substantia nigra	UBERON:0002038	84.19	gold quality
anterior cingulate cortex	UBERON:0009835	84.18	gold quality
cingulate cortex	UBERON:0003027	84.13	gold quality
palpebral conjunctiva	UBERON:0001812	84.10	gold quality
left ventricle myocardium	UBERON:0006566	84.06	silver quality
heart right ventricle	UBERON:0002080	83.91	gold quality
amniotic fluid	UBERON:0000173	83.89	gold quality
amygdala	UBERON:0001876	83.80	gold quality
CA1 field of hippocampus	UBERON:0003881	83.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.61	gold quality
mammalian vulva	UBERON:0000997	83.57	gold quality
brain	UBERON:0000955	83.54	gold quality
hypothalamus	UBERON:0001898	83.52	gold quality
caudate nucleus	UBERON:0001873	83.49	gold quality
upper leg skin	UBERON:0004262	83.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.39	gold quality
islet of Langerhans	UBERON:0000006	83.15	gold quality
pylorus	UBERON:0001166	83.00	gold quality
putamen	UBERON:0001874	82.98	gold quality
myocardium	UBERON:0002349	82.93	silver quality
buccal mucosa cell	CL:0002336	82.63	gold quality
secondary oocyte	CL:0000655	82.62	gold quality
corpus callosum	UBERON:0002336	82.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.44	gold quality
oral cavity	UBERON:0000167	82.43	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.42	gold quality
pericardium	UBERON:0002407	82.20	gold quality
monocyte	CL:0000576	82.18	gold quality
mononuclear cell	CL:0000842	82.10	gold quality
leukocyte	CL:0000738	81.95	gold quality
epithelium of esophagus	UBERON:0001976	81.91	gold quality
smooth muscle tissue	UBERON:0001135	81.87	gold quality
urethra	UBERON:0000057	81.72	gold quality
ventricular zone	UBERON:0003053	81.47	gold quality
blood vessel layer	UBERON:0004797	81.44	gold quality
right frontal lobe	UBERON:0002810	81.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.21	gold quality
gingiva	UBERON:0001828	81.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29
E-GEOD-124858	no	506.90

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	89.2	high
Somatosensory cortex	tissue	89.2
Occipital cortex	tissue	85.5
Motor cortex	tissue	82.3
Putamen	tissue	80.9
Prefrontal cortex	tissue	78.9
Pons	tissue	77.1
Retrosplenial and cingulate cortex	tissue	76.3
Thalamus	tissue	75.2
Hippocampal formation	tissue	74.6
Entorhinal cortex	tissue	74.6
Temporal cortex	tissue	70.7
Retrosplenial cortex	tissue	69.9
Midbrain	tissue	67.3
Superior colliculi	tissue	66.1
Substantia nigra	tissue	65.3
Insular cortex	tissue	65.3
Periaqueductal gray	tissue	63.4
Hypothalamus	tissue	63.2
Septum	tissue	63.2
Medulla oblongata	tissue	61.8
Ventral forebrain	tissue	61.2
Postcentral gyrus	tissue	60.3
Locus coeruleus	tissue	59.9
Amygdala	tissue	59.6
Basal ganglia	tissue	57.6	medium
Spinal cord	tissue	55.8
Nucleus accumbens	tissue	53.1
Hippocampus	tissue	49.5	medium
Choroid plexus	tissue	39.2
Cerebellum	tissue	33.2	medium
Olfactory bulb	tissue	32.5
Corpus callosum	tissue	31.3
Frontal cortex	tissue	26.5
Caudate putamen	tissue	25.9
Liver	tissue	11.8	not detected
Smooth muscle	tissue	10.5	medium
Thymus	tissue	9.5
Parathyroid gland	tissue	8.3	medium
Gallbladder	tissue	8.3	low
Rectum	tissue	8.0	medium
Adrenal gland	tissue	7.5	medium
Seminal vesicle	tissue	7.2	low
Thyroid gland	tissue	7.0	medium
Lymph node	tissue	6.9	medium
Spleen	tissue	6.5	low
Esophagus	tissue	6.3	low
Tonsil	tissue	6.0	low
Colon	tissue	5.9	low
Epididymis	tissue	5.9	low
Skin 1	tissue	5.8	low
Urinary bladder	tissue	5.8	low
Kidney	tissue	5.8	medium
Heart muscle	tissue	5.7	low
Retina	tissue	5.7
Breast	tissue	5.5	low
Lung	tissue	5.5	medium
Prostate	tissue	5.5	low
Cervix	tissue	5.4	medium
Fallopian tube	tissue	5.4	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Subiculum (72.8), Ventral hippocampus (65.5), Dorsal hippocampus (64.1), Precentral gyrus, middle (62.9), Temporal pole (61.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, ZNF91

miRNA regulators (miRDB)

Targeting ZMAT3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 334 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955

Functional genomics

gnomAD constraint: pLI 0.00831, LOEUF 0.759, missense Z 0.906 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000311417 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 17)

• Results demonstrate that human Wig-1 can bind different types of double-stranded RNAs (dsRNAs), including dsRNAs resembling small interfering RNAs and microRNAs, and indicate that dsRNA binding has a role in Wig-1-mediated regulation of cell growth. (PMID:16844115)
• Wig-1-binding proteins, hnRNP A2/B1 and RNA Helicase A, both of which are involved in RNA processing, were identified. (PMID:18519039)
• Data demonstrated a direct interaction between Dicer and Wig-1 and both may play a common role in dsRNA-related gene regulation. (PMID:19127773)
• the p53 target Wig-1 is a previously undescribed AU-rich element-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response (PMID:19805223)
• The cellular distribution of the nuclear matrix protein matrin 3 is altered by novel phosphorylation induced by the alphaherpesvirus US3 kinase family. (PMID:20962082)
• WIG-1 might be a novel modifier in esophageal carcinogenesis, and the WIG-1 MAb should be useful in further study of the mechanism in WIG-1-related physiological reactions. (PMID:21050045)
• WIG-1 might be involved in the zinc-induced cell cycle arrest and apoptosis of human esophageal squamous cell carcinoma cells (PMID:21559779)
• Wig-1 knockdown causes a dramatic inhibition of N-Myc expression and triggers differentiation in neuroblastoma cells carrying amplified N-Myc. (PMID:22513872)
• The data indicated a novel role for Wig1 in RNA-induced silencing complex target accessibility, which is a key step in RNA-mediated gene silencing. Fine tuning of p21 levels by Wig1 was essential for the prevention of cellular senescence. (PMID:23085987)
• PSF and MATR3 are cellular host factors that bind viral RNA and promote Rev activity. (PMID:23158102)
• Results suggest a role of Wig-1 as a survival factor that directs the p53 stress response toward cell cycle arrest rather than apoptosis through the regulation of FAS and 14-3-3sigma mRNA levels. (PMID:24469038)
• expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma (PMID:25379706)
• we propose that Wig1, a key p53 downstream molecule in HD condition, play an important role in stabilizing mutant Htt mRNA and thereby accelerating HD pathology in the mHtt-p53-Wig1 positive feedback manner (PMID:27206983)
• WIG1 governs the miRNA-dependent and the miRNA-independent recruitment of AGO2 to lower the stability of and suppress the translation of ACOT7 mRNA. (PMID:28472401)
• Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program. (PMID:33157015)
• The p53-induced RNA-binding protein ZMAT3 is a splicing regulator that inhibits the splicing of oncogenic CD44 variants in colorectal carcinoma. (PMID:33334821)
• eIF5B regulates the expression of PD-L1 in prostate cancer cells by interacting with Wig1. (PMID:34525951)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zmat3	ENSDARG00000080021
mus_musculus	Zmat3	ENSMUSG00000027663
rattus_norvegicus	Zmat3	ENSRNOG00000063864
drosophila_melanogaster	CG1231	FBGN0035134
drosophila_melanogaster	dbf	FBGN0287630

Paralogs (9): ZNF346 (ENSG00000113761), ZNF385B (ENSG00000144331), ZMAT2 (ENSG00000146007), ZNF385D (ENSG00000151789), ZNF385A (ENSG00000161642), ZMAT4 (ENSG00000165061), ZMAT1 (ENSG00000166432), KRCC1 (ENSG00000172086), ZNF385C (ENSG00000187595)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0VD35	97.8%	Diamond
Xenopus tropicalis	B0JZ85	84.7%	Diamond
Xenopus laevis	Q8AVN9	84.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KCNMB3	protein-coding	27094
PIK3CA	protein-coding	5290
LINC01014	ncRNA	100874330
KCNMB2-AS1	ncRNA	104797538
KCNMB2	protein-coding	10242
PIK3CA-DT	ncRNA	101928739
ZNF639	protein-coding	51193

Protein

Protein identifiers

Zinc finger matrin-type protein 3 — Q9HA38 (reviewed: Q9HA38)

Alternative names: Zinc finger protein WIG-1, p53-activated gene 608 protein

All UniProt accessions (3): A0A494C120, C9J8H5, Q9HA38

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a bona fide target gene of p53/TP53. May play a role in the TP53-dependent growth regulatory pathway. May contribute to TP53-mediated apoptosis by regulation of TP53 expression and translocation to the nucleus and nucleolus.

Subunit / interactions. Interacts with dsRNA.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Highly expressed in adult brain, and moderately in adult kidney and testis. Not detected in fetal brain, heart, pancreas, adrenal gland, liver or small intestine.

Induction. By DNA damage in a p53/TP53-dependent manner. Up-regulated following ionizing radiation in primary squamous cell carcinoma of the lung and in various colon cancer cell lines.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HA38-1	1	yes
Q9HA38-2	2

RefSeq proteins (8): NP_001362753, NP_001362754, NP_001362755, NP_001362756, NP_001362757, NP_001362758, NP_071915, NP_689426 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR013087	Zf-C2H2_type	Domain
IPR022755	Znf_C2H2_jaz	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR052644	ZMAT3	Family

Pfam: PF12171, PF12874

UniProt features (10 total): zinc finger region 3, compositionally biased region 3, region of interest 2, chain 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HA38-F1	69.64	0.27

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 304 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, TGCGCANK_UNKNOWN, GCANCTGNY_MYOD_Q6, GOLDRATH_IMMUNE_MEMORY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, TGACCTY_ERR1_Q2, AAAYRNCTG_UNKNOWN, chr3q26, CAGCTG_AP4_Q5, TANG_SENESCENCE_TP53_TARGETS_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GROSS_ELK3_TARGETS_UP, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN

GO Biological Process (3): apoptotic process (GO:0006915), DNA damage response (GO:0006974), protein transport (GO:0015031)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

15 GO namespaces:

Category	Terms
binding	2
nuclear lumen	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 474 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZMAT3	TP53	P04637	696
ZMAT3	SESN1	Q9Y6P5	567
ZMAT3	CDKN1A	P38936	512
ZMAT3	PHLDA3	Q9Y5J5	500
ZMAT3	MDM4	O15151	498
ZMAT3	CCNG1	P51959	497
ZMAT3	AEN	Q8WTP8	495
ZMAT3	RPS27L	Q71UM5	492
ZMAT3	BBC3	Q96PG8	482
ZMAT3	MDM2	Q00987	472
ZMAT3	DDB2	Q92466	469
ZMAT3	PERP	Q96FX8	456
ZMAT3	TIGAR	Q9NQ88	455
ZMAT3	FDXR	P22570	442
ZMAT3	PMAIP1	Q13794	441

IntAct

Human interaction partners of ZMAT3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
AGO2	direct interaction	0.600	5
PRKRA	physical association	0.560	3
SIAH1	physical association	0.560	3
STAU1	physical association	0.560	3
TARBP2	physical association	0.560	3
ACTA2	association	0.530	2
DHX9	physical association	0.520	3
HNRNPA2B1	physical association	0.520	3
NS	physical association	0.370	2

BioGRID (46 interactions; top human partners by supporting records): TARBP2 (Affinity Capture-MS; 4 records), ACTA2 (Affinity Capture-MS; 3 records), DCAF17 (Affinity Capture-MS; 3 records), FTO (Affinity Capture-MS; 3 records), DHX9 (Affinity Capture-Western; 2 records), HNRNPA2B1 (Affinity Capture-Western; 2 records), ISCA1 (Affinity Capture-MS; 2 records), SUPV3L1 (Affinity Capture-MS; 2 records), APP (Reconstituted Complex), CHD8 (Affinity Capture-MS), CNOT6 (Affinity Capture-Western), DICER1 (Affinity Capture-MS), ELAVL1 (Affinity Capture-RNA), EMC2 (Affinity Capture-MS), EZH2 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ZMAT3: 47 ClinVar records (0 pathogenic / likely pathogenic); 11 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 587):

Position(s)	Effect	Δscore	Sites
3:179025046	donor_gain	1.0000
3:179027699	donor_gain	1.0000
3:179030878–179030879	donor_loss	1.0000	6
3:179070850	donor_gain	1.0000
3:179025013	donor_gain	0.9900
3:179027421–179027422	donor_loss	0.9900	5
3:179027489	donor_gain	0.9900
3:179027524–179027525	acceptor_loss	0.9900	6
3:179027654	donor_gain	0.9900
3:179027813–179027814	acceptor_loss	0.9900	6

AlphaMissense

749 missense substitutions predicted likely pathogenic (of 1,882 scored), across 152 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M283	9	0.927	0.988
M238	9	0.879	0.988
H88	8	0.999	1.000
H165	8	0.999	1.000
H171	8	0.999	1.000
H94	8	0.998	1.000
H270	8	0.997	0.999
F156	8	0.996	1.000
H264	8	0.994	0.999
D235	8	0.989	0.997
F261	8	0.985	1.000
D147	8	0.962	0.990
N80	8	0.948	0.998
N170	8	0.948	0.998
D153	8	0.942	0.995
N93	8	0.941	0.998
S157	8	0.932	0.999
S243	8	0.882	0.997
C72	7	1.000	1.000
C75	7	1.000	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	1.16e-05
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	2.22e-05
Lung Adenocarcinoma (validation)	unfavorable	0.000105

Disease associations

OMIM: gene MIM:606452 | disease phenotypes:

GWAS associations

11 associations:

Study	Trait	p-value
GCST90002390_91	Mean corpuscular hemoglobin	1e-21
GCST90002392_345	Mean corpuscular volume	1e-20
GCST90002397_684	Mean spheric corpuscular volume	3e-15
GCST90002395_282	Mean platelet volume	5e-15
GCST90002401_435	Platelet distribution width	3e-14
GCST004603_185	Platelet count	4e-12
GCST004630_133	Mean corpuscular hemoglobin	3e-10
GCST010002_445	Refractive error	2e-9
GCST004602_89	Mean corpuscular volume	6e-9
GCST002037_18	Post-traumatic stress disorder (asjusted for relatedness)	2e-6
GCST009391_767	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects cotreatment, increases expression	6
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	6
Cisplatin	affects expression, decreases expression, increases expression, affects cotreatment	5
methylmercuric chloride	increases expression, affects cotreatment	4
Doxorubicin	affects expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
mercuric bromide	affects cotreatment, increases expression	2
nutlin 3	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Daunorubicin	increases expression	2
Mitoxantrone	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases expression, affects expression, affects cotreatment, increases abundance	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
benzo(b)fluoranthene	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
salinomycin	decreases expression	1
cobaltous chloride	increases expression	1
potassium bromate	increases expression	1
zinc chromate	increases abundance, increases expression	1
fludarabine	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	decreases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2LR	Abcam HeLa ZMAT3 KO	Cancer cell line	Female
CVCL_D8YE	Ubigene HCT 116 ZMAT3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	Phase 4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide
NCT02405858	Phase 4	COMPLETED	A Study of Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer Participants Who Responded Poorly to the First-line Combined Androgen Blockade Therapy
NCT02441517	Phase 4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
NCT02441894	Phase 4	COMPLETED	Combination of Cabazitaxel With Prednisolone With Primary Prophylaxis With PEG-G-CSF in Treatment of Patients With Prostate Cancer
NCT02475057	Phase 4	COMPLETED	Endothelial Function in Prostate Cancer Patients on Degarelix vs. Luteinizing Hormone-Releasing Hormone Agonists
NCT02511665	Phase 4	UNKNOWN	Metformin And Longevity
NCT02651948	Phase 4	COMPLETED	Transperineal, MRI-guided, Prostate Biopsy
NCT02721433	Phase 4	COMPLETED	4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases
NCT02726009	Phase 4	COMPLETED	A Trial to Evaluate Safety of Firmagon® (Degarelix) in Indian Patients Diagnosed With Advanced Hormone-dependent Prostate Cancer
NCT02749825	Phase 4	TERMINATED	Comparison of Trelstar Versus Lupron or Zoladex in Advanced Prostate Cancer
NCT02757365	Phase 4	UNKNOWN	Efficiency Study of Aspirin to Prevent the Occurrence of Prostate Cancer
NCT02773251	Phase 4	COMPLETED	The Effect of Guardix-solution for the Prevention of Postoperative Intestinal Adhesion and Intestinal Obstruction After Laparoscopic Pelvic Cavity Surgery
NCT02812186	Phase 4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery