ZNF423

Summary

ZNF423 (zinc finger protein 423, HGNC:16762) is a protein-coding gene on chromosome 16q12.1, encoding Zinc finger protein 423 (Q2M1K9). Transcription factor that can both act as an activator or a repressor depending on the context.

The protein encoded by this gene is a nuclear protein that belongs to the family of Kruppel-like C2H2 zinc finger proteins. It functions as a DNA-binding transcription factor by using distinct zinc fingers in different signaling pathways. Thus, it is thought that this gene may have multiple roles in signal transduction during development. Mutations in this gene are associated with nephronophthisis-14 and Joubert syndrome-19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23090 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephronophthisis 14 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 32
• Clinical variants (ClinVar): 969 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 43
• MANE Select transcript: NM_001379286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16762
Approved symbol	ZNF423
Name	zinc finger protein 423
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0760, OAZ, hOAZ, Ebfaz, Zfp104, NPHP14, JBTS19
Ensembl gene	ENSG00000102935
Ensembl biotype	protein_coding
OMIM	604557
Entrez	23090

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000535559, ENST00000561648, ENST00000562520, ENST00000562871, ENST00000563137, ENST00000567169, ENST00000568094

RefSeq mRNA: 4 — MANE Select: NM_001379286 NM_001271620, NM_001330533, NM_001379286, NM_015069

CCDS: CCDS32445, CCDS61930, CCDS81979, CCDS92157

Canonical transcript exons

ENST00000563137 — 8 exons

Exon	Start	End
ENSE00001207205	49626170	49626254
ENSE00001218718	49523624	49523739
ENSE00001593800	49525363	49525494
ENSE00002600103	49855735	49856112
ENSE00002603121	49487524	49491304
ENSE00003571874	49730771	49730971
ENSE00003640476	49789487	49789546
ENSE00003650454	49635660	49638874

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.40.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7346 / max 789.4488, expressed in 700 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157295	4.9648	661
157293	0.3080	179
157288	0.1664	77
157294	0.1328	85
157289	0.1112	56
157290	0.0324	6
157302	0.0192	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.40	gold quality
biceps brachii	UBERON:0001507	96.15	gold quality
cartilage tissue	UBERON:0002418	95.02	gold quality
cauda epididymis	UBERON:0004360	94.25	gold quality
ganglionic eminence	UBERON:0004023	93.86	gold quality
skin of hip	UBERON:0001554	93.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.62	gold quality
embryo	UBERON:0000922	93.56	gold quality
cranial nerve II	UBERON:0000941	92.99	gold quality
vastus lateralis	UBERON:0001379	92.46	gold quality
buccal mucosa cell	CL:0002336	92.32	silver quality
caput epididymis	UBERON:0004358	91.62	gold quality
quadriceps femoris	UBERON:0001377	91.53	gold quality
gluteal muscle	UBERON:0002000	90.37	gold quality
medial globus pallidus	UBERON:0002477	89.62	gold quality
skeletal muscle tissue	UBERON:0001134	89.30	gold quality
parietal pleura	UBERON:0002400	89.19	silver quality
seminal vesicle	UBERON:0000998	88.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.03	gold quality
triceps brachii	UBERON:0001509	87.92	silver quality
pleura	UBERON:0000977	87.87	silver quality
muscle tissue	UBERON:0002385	87.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.75	gold quality
ventricular zone	UBERON:0003053	87.52	gold quality
corpus epididymis	UBERON:0004359	87.36	gold quality
urethra	UBERON:0000057	87.27	gold quality
muscle organ	UBERON:0001630	86.94	gold quality
mammary duct	UBERON:0001765	86.42	gold quality
tendon of biceps brachii	UBERON:0008188	86.42	gold quality
visceral pleura	UBERON:0002401	86.25	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BRCA1	Unknown
HES5
OAZ3
PPARG	Activation
ZNF521

JASPAR motifs

Motif	Name	Family
MA0116.2	ZNF423	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:33646306

Upstream regulators (CollecTRI, top): EZH2, ZNF521

miRNA regulators (miRDB)

124 targeting ZNF423, 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-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973

Literature-anchored findings (GeneRIF, showing 15)

• Low ZNF423 expression is associated with neuroblastoma. (PMID:19345331)
• The expression level of OAZ mRNA in the bone marrow and peripheral blood of SLE patients was significantly increased than those observed in normal controls. (PMID:20017333)
• Elevated expression of OAZ transcripts in systemic lupus erythematosus PBLs were strongly correlated with disease activity. (PMID:20359360)
• Study identifies by whole-exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing Nephronophthisis-related ciliopathies. (PMID:22863007)
• These findings suggest that expression of UBR5-ZNF423 protein might contribute to the transformation of a subset of Nasopharyngeal carcinoma (PMID:23878065)
• ZNF423 expression is associated with poor outcome of ETV6-RUNX1-negative B precursor acute lymphoblastic leukemia patients. (PMID:24081948)
• ZNF423 is a target for epigenetic deregulation and BMP2-dependent pathways in childhood B precursor acute lymphoblastic leukemia. Aberrant ZNF423 inhibits EBF-1 target genes, leads to a B cell maturation arrest in vivo and is associated with poor outcome of ETV6-RUNX1-negative acute lymphoblastic leukemia. (PMID:24081948)
• OAZ gene expression was highly enriched in mesenchymal stem cells (MSCs) compared with peripheral blood leukocytes and was increased in patients with systemic lupus erythematosus (SLE) compared with control subjects. (PMID:25219468)
• two multi-zinc finger transcription cofactors named ZNF423 and ZNF521 have been characterised as potent inhibitors of EBF1 and are emerging as potentially relevant contributors to the development of B-cell leukaemias (PMID:26788497)
• We identified calmodulin-like protein 3 (CALML3) as a key sensor of this SNP and a coregulator of ERalpha, which contributes to differential gene transcription regulation in an estrogen and SERM-dependent fashion. Furthermore, using CRISPR/Cas9-engineered ZR75-1 breast cancer cells with different ZNF423 SNP genotypes, striking differences in cellular responses to SERMs and PARP inhibitors, alone or in combination (PMID:28821270)
• We report that CTSO reduces the protein levels of BRCA1 and ZNF423 through cysteine proteinase-mediated degradation. We also have identified a series of transcription factors of BRCA1 that are regulated by CTSO at the protein level. (PMID:28968398)
• Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease. (PMID:31283791)
• The present study denoted that ZNF423 is an oxidative stress-responsive gene with an oncogenic property contributing to the regulation of CCA genesis. (PMID:31284679)
• ZNF423 patient variants, truncations, and in-frame deletions in mice define an allele-dependent range of midline brain abnormalities. (PMID:32925911)
• Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma. (PMID:35313831)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf423	ENSDARG00000095732
mus_musculus	Zfp423	ENSMUSG00000045333
rattus_norvegicus	Zfp423	ENSRNOG00000014658
drosophila_melanogaster	CG12769	FBGN0033252
caenorhabditis_elegans		WBGENE00001223
caenorhabditis_elegans		WBGENE00017406
caenorhabditis_elegans		WBGENE00019960

Paralogs (7): ZNF211 (ENSG00000121417), ZNF462 (ENSG00000148143), ZBTB39 (ENSG00000166860), ZNF597 (ENSG00000167981), ZNF445 (ENSG00000185219), ZNF786 (ENSG00000197362), ZNF521 (ENSG00000198795)

Protein

Protein identifiers

Zinc finger protein 423 — Q2M1K9 (reviewed: Q2M1K9)

Alternative names: Olf1/EBF-associated zinc finger protein, Smad- and Olf-interacting zinc finger protein

All UniProt accessions (4): Q2M1K9, A0A087WV99, A0A7P0Q1F0, F5H7S1

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that can both act as an activator or a repressor depending on the context. Plays a central role in BMP signaling and olfactory neurogenesis. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved in terminal olfactory receptor neurons differentiation; this interaction preventing EBF1 to bind DNA and activate olfactory-specific genes. Involved in olfactory neurogenesis by participating in a developmental switch that regulates the transition from differentiation to maturation in olfactory receptor neurons. Controls proliferation and differentiation of neural precursors in cerebellar vermis formation.

Subunit / interactions. Homodimer. Interacts with EBF1. Interacts with SMAD1 and SMAD4. Interacts with PARP1. Interacts with CEP290.

Subcellular location. Nucleus.

Tissue specificity. Expressed in brain, lung, skeletal muscle, heart, pancreas and kidney but not liver or placenta. Also expressed in aorta, ovary, pituitary, small intestine, fetal brain, fetal kidney and, within the adult brain, in the substantia nigra, medulla, amygdala, thalamus and cerebellum.

Disease relevance. Nephronophthisis 14 (NPHP14) [MIM:614844] An autosomal recessive disorder manifesting as infantile-onset kidney disease, cerebellar vermis hypoplasia, and situs inversus. Nephronophthisis is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. The disease is caused by variants affecting the gene represented in this entry. Joubert syndrome 19 (JBTS19) [MIM:614844] A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). JBTS19 patients have polycystic kidney disease, Leber congenital amaurosis, cerebellar vermis hypoplasia, and breathing abnormality. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and Olf signaling pathways. C2H2-type zinc fingers 14-19 mediate the interaction with SMAD1 and SMAD4, while zinc fingers 28-30 mediate the interaction with EBF1. zinc fingers 2-8 bind the 5’-CCGCCC-3’ DNA sequence in concert with EBF1, while zinc fingers 9-13 bind BMP target gene promoters in concert with SMADs.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2M1K9-1	1	yes
Q2M1K9-2	2

RefSeq proteins (4): NP_001258549, NP_001317462, NP_001366215, NP_055884 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13912

UniProt features (67 total): zinc finger region 30, mutagenesis site 10, compositionally biased region 6, region of interest 5, modified residue 4, strand 4, sequence variant 3, helix 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2MDG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M1K9-F1	61.63	0.00

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 (4): 47, 50, 604, 1054

Mutagenesis-validated functional residues (10):

Position	Phenotype
420	abolishes the ability to bind promoter of bmp target genes; when associated with a-426; a-452; a-458; a-491; a-497; a-52
426	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-452; a-458; a-491; a-497; a-52
452	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-458; a-491; a-497; a-52
458	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-491; a-497; a-52
491	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-458; a-497; a-52
497	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-458; a-491; a-52
528	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-458; a-491; a-49
534	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-458; a-491; a-49
574	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-458; a-491; a-49
581	abolishes the ability to bind promoter of bmp target genes; when associated with a-420; a-426; a-452; a-458; a-491; a-49

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2

MSigDB gene sets: 283 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, YAATNRNNNYNATT_UNKNOWN, NKX25_02, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, TATTATA_MIR374, ACTGCAG_MIR173P, CHX10_01, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, NFKB_Q6, GOBP_POSITIVE_REGULATION_OF_BMP_SIGNALING_PATHWAY, CEBP_Q2, CATRRAGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MODULE_195

GO Biological Process (16): regulation of DNA-templated transcription (GO:0006355), Notch signaling pathway (GO:0007219), nervous system development (GO:0007399), cell differentiation (GO:0030154), positive regulation of BMP signaling pathway (GO:0030513), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), protein localization to cilium (GO:0061512), negative regulation of cold-induced thermogenesis (GO:0120163), regulation of transcription by RNA polymerase II (GO:0006357), smoothened signaling pathway (GO:0007224), cerebellar granule cell precursor proliferation (GO:0021930), regulation of cerebellar granule cell precursor proliferation (GO:0021936), white fat cell differentiation (GO:0050872), brown fat cell differentiation (GO:0050873), cilium assembly (GO:0060271)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional regulation of brown and beige adipocyte differentiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
cell surface receptor signaling pathway	2
fat cell differentiation	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
system development	1
cellular developmental process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
protein localization to organelle	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
transcription by RNA polymerase II	1
cell proliferation in external granule layer	1
cerebellar granule cell precursor proliferation	1
regulation of neural precursor cell proliferation	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF423	EBF1	Q9UH73	967
ZNF423	EBF2	Q9HAK2	840
ZNF423	SMAD4	Q13485	715
ZNF423	PPARG	P37231	703
ZNF423	FABP4	P15090	667
ZNF423	CEP290	O15078	604
ZNF423	EBF4	Q9BQW3	577
ZNF423	EBF3	Q9H4W6	557
ZNF423	CEBPA	P49715	543
ZNF423	CTSO	P43234	541
ZNF423	NEK8	Q86SG6	533
ZNF423	UCP1	P25874	507
ZNF423	RARA	P10276	504
ZNF423	SMAD1	Q15797	495
ZNF423	CEP164	Q9UPV0	488

IntAct

41 interactions, top by confidence:

A	B	Type	Score
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
ZNF521	ZNF423	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	CDK2AP1	psi-mi:“MI:0914”(association)	0.530
ZG16B	ITIH2	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
ZNF423	RARA	psi-mi:“MI:0915”(physical association)	0.520
RARA	ZNF423	psi-mi:“MI:0915”(physical association)	0.520
ZNF423	CEP290	psi-mi:“MI:0915”(physical association)	0.510
MTA1	H3C1	psi-mi:“MI:0914”(association)	0.480
ZNF423	RXRA	psi-mi:“MI:0915”(physical association)	0.400
ZNF423	RARB	psi-mi:“MI:0915”(physical association)	0.400
RARG	ZNF423	psi-mi:“MI:0915”(physical association)	0.400
ZNF423	PARP1	psi-mi:“MI:0915”(physical association)	0.400
PARP1	ZNF423	psi-mi:“MI:0915”(physical association)	0.400
ZNF423	FXR1	psi-mi:“MI:0915”(physical association)	0.370
ZNF423	TSC1	psi-mi:“MI:0915”(physical association)	0.370
MTA1	RBBP4	psi-mi:“MI:0914”(association)	0.350
MAP4K3	ZNF423	psi-mi:“MI:0914”(association)	0.350
HDAC1		psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
ZNF17	TRIM24	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): BRCA1 (Two-hybrid), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), PARP1 (Affinity Capture-Western), PARP1 (Two-hybrid), SMAD4 (Affinity Capture-Western), SMAD1 (Affinity Capture-Western), ZNF423 (Co-purification)

ESM2 similar proteins: A0JPB4, A1L1J6, A1L1R6, A1Z9R4, A2A935, A4IFJ6, E9Q6W4, E9Q8T2, G5E8B9, O08961, O13089, O15060, O42410, O57415, O73590, O95625, P14404, P57071, Q03112, Q03267, Q09452, Q13422, Q1L8W0, Q2M1K9, Q5DU09, Q5R9W9, Q5T0B9, Q5ZLR2, Q60821, Q62947, Q64318, Q6DBW0, Q6GNP2, Q6INV8, Q6KAS7, Q6NRM0, Q6NUD7, Q7TS63, Q802Y8, Q80TS5

Diamond homologs: A1L1R6, A1Z9R4, O08961, Q2M1K9, Q6KAS7, Q6NUD7, Q80TS5, Q96K83

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
miR-23a	“down-regulates quantity”	ZNF423	“post transcriptional regulation”
ZNF423	“up-regulates activity”	Adipogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	6	71.4×	3e-08
NuRD complex assembly	9	39.6×	2e-10
RNA Polymerase I Transcription Initiation	5	35.0×	1e-05
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	6	28.6×	3e-06
Regulation of PTEN gene transcription	5	27.9×	3e-05
Interaction of NuRD complexes with transcription factors	7	27.8×	5e-07
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	22.9×	6e-05
HDACs deacetylate histones	6	22.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	5	103.5×	2e-07
chromatin remodeling	6	11.8×	4e-04
negative regulation of cell population proliferation	6	6.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	493
Likely benign	401
Benign	28

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
280335	NM_001379286.1(ZNF423):c.3189dup (p.Asn1064fs)	Pathogenic
37288	NM_001379286.1(ZNF423):c.1542del (p.Asn515fs)	Pathogenic
37289	NM_001379286.1(ZNF423):c.3853C>T (p.His1285Tyr)	Pathogenic
59468	GRCh38/hg38 16q11.2-12.1(chr16:46466829-51673196)x1	Pathogenic
689798	NM_001379286.1(ZNF423):c.2555G>A (p.Gly852Glu)	Likely pathogenic

SpliceAI

4330 predictions. Top by Δscore:

Variant	Effect	Δscore
16:49523737:AGA:A	acceptor_gain	1.0000
16:49523738:GA:G	acceptor_gain	1.0000
16:49523740:C:CC	acceptor_gain	1.0000
16:49525359:TTA:T	donor_loss	1.0000
16:49525362:CC:C	donor_loss	1.0000
16:49525490:TTCCT:T	acceptor_gain	1.0000
16:49525491:TCCT:T	acceptor_gain	1.0000
16:49525492:CCTC:C	acceptor_gain	1.0000
16:49525493:CT:C	acceptor_gain	1.0000
16:49525493:CTCT:C	acceptor_loss	1.0000
16:49525495:C:A	acceptor_loss	1.0000
16:49525495:C:CC	acceptor_gain	1.0000
16:49525496:T:A	acceptor_loss	1.0000
16:49626164:TCTTA:T	donor_loss	1.0000
16:49626165:CTTA:C	donor_loss	1.0000
16:49626166:TTACC:T	donor_loss	1.0000
16:49626167:TACCA:T	donor_loss	1.0000
16:49626168:A:AC	donor_gain	1.0000
16:49626168:ACCA:A	donor_loss	1.0000
16:49626169:C:CC	donor_gain	1.0000
16:49626169:C:T	donor_loss	1.0000
16:49626169:CCAAT:C	donor_gain	1.0000
16:49626250:TTTTT:T	acceptor_gain	1.0000
16:49626251:TTTT:T	acceptor_gain	1.0000
16:49626252:TTT:T	acceptor_gain	1.0000
16:49626253:TT:T	acceptor_gain	1.0000
16:49626253:TTCTG:T	acceptor_loss	1.0000
16:49626254:TCTG:T	acceptor_loss	1.0000
16:49626255:C:CA	acceptor_loss	1.0000
16:49626255:C:CC	acceptor_gain	1.0000

AlphaMissense

8719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:49523657:G:C	C1264W	1.000
16:49523659:A:G	C1264R	1.000
16:49523666:G:C	C1261W	1.000
16:49523668:A:G	C1261R	1.000
16:49523695:G:C	H1252D	1.000
16:49523708:G:C	H1247Q	1.000
16:49523708:G:T	H1247Q	1.000
16:49523709:T:G	H1247P	1.000
16:49523710:G:C	H1247D	1.000
16:49523718:A:C	L1244W	1.000
16:49523718:A:G	L1244S	1.000
16:49523735:G:C	F1238L	1.000
16:49523735:G:T	F1238L	1.000
16:49523736:A:G	F1238S	1.000
16:49523737:A:G	F1238L	1.000
16:49525370:A:C	C1234W	1.000
16:49525371:C:A	C1234F	1.000
16:49525371:C:G	C1234S	1.000
16:49525371:C:T	C1234Y	1.000
16:49525372:A:G	C1234R	1.000
16:49525372:A:T	C1234S	1.000
16:49525379:G:C	C1231W	1.000
16:49525380:C:G	C1231S	1.000
16:49525380:C:T	C1231Y	1.000
16:49525381:A:G	C1231R	1.000
16:49525381:A:T	C1231S	1.000
16:49525385:G:C	F1229L	1.000
16:49525385:G:T	F1229L	1.000
16:49525387:A:G	F1229L	1.000
16:49525412:G:C	H1220Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000023193 (16:49737646 G>A), RS1000029036 (16:49785589 C>G), RS1000031877 (16:49536193 T>A,C), RS1000035806 (16:49805599 C>T), RS1000048336 (16:49766752 G>A,C), RS1000052324 (16:49499627 C>A,T), RS1000054053 (16:49619504 C>G,T), RS1000060190 (16:49626793 T>A), RS1000066087 (16:49844907 T>C), RS1000075370 (16:49805626 A>G), RS1000092414 (16:49793407 C>T), RS1000101326 (16:49738834 C>A), RS1000101868 (16:49494783 T>C), RS1000106742 (16:49612305 A>G), RS1000107527 (16:49796204 G>A,C)

Disease associations

OMIM: gene MIM:604557 | disease phenotypes: MIM:614844, MIM:600334

GenCC curated gene-disease

Disease	Classification	Inheritance
nephronophthisis 14	Strong	Autosomal recessive
ciliopathy	Moderate	Autosomal recessive
Joubert syndrome with oculorenal defect	Supportive	Autosomal recessive
nephronophthisis 2	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Moderate	AR

Mondo (9): nephronophthisis 14 (MONDO:0013916), ciliopathy (MONDO:0005308), optic atrophy (MONDO:0003608), inherited retinal dystrophy (MONDO:0019118), Joubert syndrome 19 (MONDO:0800363), tibial muscular dystrophy (MONDO:0010870), chronic kidney disease (MONDO:0005300), Joubert syndrome with oculorenal defect (MONDO:0009480), nephronophthisis 2 (MONDO:0011190)

Orphanet (4): Joubert syndrome with oculorenal defect (Orphanet:2318), Ciliopathy (Orphanet:363250), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Tibial muscular dystrophy (Orphanet:609)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000090	Nephronophthisis
HP:0000112	Nephropathy
HP:0000113	Polycystic kidney dysplasia
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000358	Posteriorly rotated ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000556	Retinal dystrophy
HP:0000567	Chorioretinal coloboma
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000729	Autistic behavior
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001320	Cerebellar vermis hypoplasia

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000279_12	Inattentive symptoms	3.000000e-06
GCST002782_258	Waist-to-hip ratio adjusted for body mass index	4.000000e-06
GCST002782_259	Waist-to-hip ratio adjusted for body mass index	6.000000e-06
GCST004063_160	Waist circumference adjusted for body mass index	5.000000e-07
GCST004063_57	Waist circumference adjusted for body mass index	5.000000e-08
GCST004072_2	Cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with severe ocular complications	2.000000e-07
GCST004072_3	Cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with severe ocular complications	1.000000e-07
GCST004500_116	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	4.000000e-07
GCST004501_85	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	1.000000e-06
GCST004504_33	Waist circumference adjusted for BMI in non-smokers	5.000000e-07
GCST004863_77	Mosquito bite size	6.000000e-06
GCST006627_50	Diastolic blood pressure	4.000000e-11
GCST006979_655	Heel bone mineral density	4.000000e-13
GCST007323_52	Risk-taking tendency (4-domain principal component model)	5.000000e-08
GCST007326_93	Number of sexual partners	2.000000e-12
GCST007467_16	Word spelling	7.000000e-06
GCST007576_281	Chronotype	1.000000e-09
GCST007576_401	Chronotype	1.000000e-09
GCST009066_27	Mosaic loss of chromosome Y (Y chromosome dosage)	4.000000e-12
GCST009067_21	Mosaic loss of chromosome Y (Y chromosome dosage)	8.000000e-07
GCST012226_386	Waist circumference adjusted for body mass index	7.000000e-09
GCST012228_507	Waist-hip index	8.000000e-09
GCST012228_508	Waist-hip index	6.000000e-11
GCST012230_149	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST012230_150	Waist-to-hip ratio adjusted for BMI	7.000000e-11
GCST90000047_265	Age at first sexual intercourse	2.000000e-09
GCST90002397_238	Mean spheric corpuscular volume	3.000000e-11
GCST90002398_297	Neutrophil count	2.000000e-12
GCST90002403_674	Red blood cell count	7.000000e-10
GCST90002407_556	White blood cell count	4.000000e-10

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0006997	response to cold medicine
EFO:0004318	smoking behavior
EFO:0008378	mosquito bite reaction size measurement
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0005301	reading and spelling ability
EFO:0008328	chronotype measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
C537430	Arima syndrome (supp.)
C566582	Nephronophthisis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs8060157	Efficacy	3	raloxifene;tamoxifen	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8060157	ZNF423	3	0.00	1	raloxifene;tamoxifen

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	3
Valproic Acid	decreases expression, increases methylation	3
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	affects methylation, decreases expression	2
TAK-243	decreases sumoylation	1
methyleugenol	decreases expression	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
quinocetone	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation, decreases methylation, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Vorinostat	decreases expression	1
Atrazine	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Cytarabine	increases expression	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Asbestos, Crocidolite	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HD25	HEK293 eGFP-ZNF423	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03522207	PHASE4	TERMINATED	Accuracy and Efficacy of Trazodone (Desyrel) on Sleep Quality and Pain Management of TMD Patient
NCT07401745	PHASE4	ACTIVE_NOT_RECRUITING	Occlusal Splint Combined With Granisetron Injection for Management of Myofascial Pain Related to Temporomandibular Disorders
NCT00073710	PHASE4	COMPLETED	Study to Evaluate the Effects of Zemplar Injection and Calcijex on Intestinal Absorption of Calcium
NCT00125593	PHASE4	COMPLETED	Study of Heart and Renal Protection
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00155246	PHASE4	COMPLETED	Efficacy of Pentoxifylline on Chronic Kidney Disease
NCT00175149	PHASE4	TERMINATED	Active Vitamin D Effect on Left Ventricular Hypertrophy
NCT00184769	PHASE4	COMPLETED	Growth Hormone Treatment in Infants Aged 1 to 2 Years With Chronic Renal Insufficiency (CRI) and Growth Retardation.
NCT00190580	PHASE4	COMPLETED	Kanagawa Valsartan Trial (KVT): Effects of Valsartan on Renal and Cardiovascular Disease
NCT00194961	PHASE4	TERMINATED	Effect of Growth Hormone on Leptin, Cytokines and Body Composition of Children With Growth Failure Due to Chronic Kidney Disease
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00324571	PHASE4	COMPLETED	Dialysis Clinical Outcomes Revisited (DCOR) Trial
NCT00364884	PHASE4	UNKNOWN	Keto-/Amino Acid Supplemented Low Protein Diet in Patients With Chronic Kidney Disease
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00384618	PHASE4	TERMINATED	Anti-Oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study
NCT00478543	PHASE4	COMPLETED	Loop Diuretics in Chronic Kidney Disease
NCT00632125	PHASE4	COMPLETED	Post-authorization Safety Study in CKD Subjects Receiving HX575 i.v.
NCT00644046	PHASE4	COMPLETED	Chronic Kidney Disease Prevention of An-Lo District, Keelung
NCT00719316	PHASE4	UNKNOWN	Aliskiren and Muscle Sympathetic Nerve Activity
NCT00725517	PHASE4	COMPLETED	Efficacy and Safety of a 7.5% Icodextrin Peritoneal Dialysis Solution in Once-Daily Long Dwell Exchange
NCT00741585	PHASE4	COMPLETED	Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
NCT00749736	PHASE4	COMPLETED	The Role of Vitamin D in Immune Function in Patients With Chronic Kidney Disease (CKD) Stages 3 and 4.
NCT00752102	PHASE4	COMPLETED	Vitamin D and Coronary Calcification Study
NCT00756145	PHASE4	COMPLETED	The Use of Low Molecular Weight Heparin in Hemodiafiltration
NCT00768638	PHASE4	COMPLETED	Study of Atorvastatin Dose Dependent Reduction of Proteinuria
NCT00786136	PHASE4	COMPLETED	Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes
NCT00803712	PHASE4	COMPLETED	20070360 Incident Dialysis
NCT00812123	PHASE4	COMPLETED	Calcineurin Free Immunosuppression in Renal Transplant Recipients
NCT00823303	PHASE4	COMPLETED	Paricalcitol Versus Calcitriol for Efficacy and Safety in Stage 3/4 Chronic Kidney Disease (CKD) With Secondary Hyperparathyroidism (SHPT)
NCT00830037	PHASE4	TERMINATED	A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease
NCT00852969	PHASE4	COMPLETED	Niacin and Endothelial Function in Early CKD
NCT00858299	PHASE4	UNKNOWN	The Change of Urinary Angiotensinogen Excretion After Valsartan Treatment in Patients With Persistent Proteinuria
NCT00860431	PHASE4	COMPLETED	Kremezin Study Against Renal Disease Progression in Korea
NCT00882401	PHASE4	COMPLETED	Vitamin D, Chronic Kidney Disease (CKD) and the Microcirculation
NCT00889629	PHASE4	COMPLETED	Pilot Study Evaluating Doxercalciferol Replacement Therapy in Kidney Transplant Recipients
NCT00892892	PHASE4	WITHDRAWN	Sympathetic Nerve Activity in Renal Failure
NCT00893425	PHASE4	COMPLETED	Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria