ZNF423

zinc finger protein 423, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 16:49487524-49857919

Links

ENSG00000102935 ∙ NCBI:23090 ∙ OMIM:604557 ∙ HGNC:16762 ∙ Uniprot:Q2M1K9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephronophthisis 14 (Limited), mode of inheritance: Unknown
• Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
• nephronophthisis 2 (Supportive), mode of inheritance: AR
• nephronophthisis 14 (Limited), mode of inheritance: AR
• nephronophthisis 14 (Strong), mode of inheritance: AR
• nephronophthisis 14 (Limited), mode of inheritance: AD
• nephronophthisis (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 19; Nephronophthisis 14	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic; Pulmonary; Renal	22863007
The conditions can involve manifestations including renal disease and anomalous perinatal breathing

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNF423 gene.

• Nephronophthisis_14 (812 variants)
• not_specified (171 variants)
• not_provided (115 variants)
• ZNF423-related_disorder (43 variants)
• Retinal_dystrophy (4 variants)
• Optic_atrophy (4 variants)
• Ciliopathy (2 variants)
• Joubert_syndrome_19 (2 variants)
• Abnormal_brain_morphology (2 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Chronic_kidney_disease (1 variants)
• Tibial_muscular_dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNF423 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379286.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	347	13	363
missense	1	3	452	13	1	470
nonsense			1			1
start loss						0
frameshift	2		2			4
splice donor/acceptor (+/-2bp)			1			1
Total	3	3	459	360	14

Highest pathogenic variant AF is 0.00001672765

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNF423	protein_coding	protein_coding	ENST00000561648	8	370396

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000448	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.49	625	826	0.756	0.0000540	8635
Missense in Polyphen		157	300.51	0.52244		3252
Synonymous	-1.12	395	368	1.07	0.0000281	2366
Loss of Function	5.54	3	41.6	0.0722	0.00000178	516

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:10660046}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:22863007}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:22863007}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: White fat cell differentiation;Differentiation of white and brown adipocyte;White fat cell differentiation;TGF-beta Receptor Signaling;BMP2 signaling TGF-beta MV (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.0347
• rvis_EVS: -2.2
• rvis_percentile_EVS: 1.36

Haploinsufficiency Scores

• pHI: 0.580
• hipred: Y
• hipred_score: 0.792
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Zfp423
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; taste/olfaction phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;Notch signaling pathway;nervous system development;cell differentiation;positive regulation of BMP signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;negative regulation of cold-induced thermogenesis
• Cellular component: nucleus;nucleoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;metal ion binding