ZNF408

zinc finger protein 408, the group of PR/SET domain family|Zinc fingers C2H2-type

Basic information

Region (hg38): 11:46701029-46705912

Links

ENSG00000175213 ∙ NCBI:79797 ∙ OMIM:616454 ∙ HGNC:20041 ∙ Uniprot:Q9H9D4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• exudative vitreoretinopathy (Supportive), mode of inheritance: AD
• exudative vitreoretinopathy 6 (Limited), mode of inheritance: AD
• retinitis pigmentosa 72 (Moderate), mode of inheritance: AR
• exudative vitreoretinopathy 6 (Strong), mode of inheritance: AD
• retinitis pigmentosa 72 (Strong), mode of inheritance: AR
• exudative vitreoretinopathy 6 (Strong), mode of inheritance: AD
• retinitis pigmentosa 72 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Exudative vitreoretinopathy 6; Retinitis pigmentosa 72	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	Ophthalmologic	6897033; 23716654; 25882705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNF408 gene.

• not provided (445 variants)
• Inborn genetic diseases (26 variants)
• not specified (6 variants)
• Exudative vitreoretinopathy 6 (4 variants)
• Exudative vitreoretinopathy 6;Retinitis pigmentosa 72 (2 variants)
• Exudative vitreoretinopathy 1 (2 variants)
• Retinitis pigmentosa 72 (1 variants)
• Retinitis pigmentosa 72;Exudative vitreoretinopathy 6 (1 variants)
• Retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNF408 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	115	7	124
missense		2	265	5	2	274
nonsense		1	9			10
start loss			1			1
frameshift		1	13			14
inframe indel			6		1	7
splice donor/acceptor (+/-2bp)			2			2
splice region			2	8		10
non coding				12	3	15
Total	0	4	298	132	13

Highest pathogenic variant AF is 0.0000263

Variants in ZNF408

This is a list of pathogenic ClinVar variants found in the ZNF408 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-46701049-T-C			Uncertain significance (Nov 15, 2022)
11-46701051-G-A			Uncertain significance (Jun 16, 2020)
11-46701052-A-T			Uncertain significance (Apr 02, 2021)
11-46701067-T-C			Uncertain significance (Dec 20, 2019)
11-46701073-T-C			Uncertain significance (Nov 28, 2019)
11-46701077-G-C			Uncertain significance (Oct 31, 2019)
11-46701078-G-A			Uncertain significance (Jun 27, 2022)
11-46701080-G-A			Likely benign (Dec 08, 2017)
11-46701082-A-G			Likely benign (Dec 15, 2023)
11-46701083-G-C			Uncertain significance (Jan 10, 2020)
11-46701090-C-T			Likely benign (Dec 26, 2020)
11-46701091-T-A			Uncertain significance (Jul 15, 2019)
11-46701092-G-A			Likely benign (Apr 08, 2021)
11-46701093-C-T			Uncertain significance (Nov 23, 2023)
11-46701095-A-G			Likely benign (Jan 18, 2024)
11-46701098-C-T			Likely benign (Nov 03, 2022)
11-46701099-G-A			Uncertain significance (Dec 06, 2023)
11-46701109-C-T			Likely benign (Mar 12, 2022)
11-46701118-C-T			Likely benign (Dec 20, 2022)
11-46701135-G-C		not specified	Benign/Likely benign (-)
11-46701181-T-C			Benign (May 16, 2021)
11-46701385-C-T			Likely benign (Dec 16, 2023)
11-46701386-C-T			Likely benign (Jul 21, 2022)
11-46701387-TTC-T			Likely benign (Feb 01, 2022)
11-46701389-C-T			Likely benign (Oct 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNF408	protein_coding	protein_coding	ENST00000311764	5	5095

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000118	0.988	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.712	403	445	0.905	0.0000270	4583
Missense in Polyphen		141	184.07	0.76601		1761
Synonymous	-0.249	190	186	1.02	0.0000104	1557
Loss of Function	2.29	14	26.8	0.522	0.00000157	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000448	0.000448
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000271	0.000264
Middle Eastern	0.000219	0.000217
South Asian	0.000167	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in transcriptional regulation.
• Disease: DISEASE: Retinitis pigmentosa 72 (RP72) [MIM:616469]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:25882705}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0911

Intolerance Scores

• loftool: 0.729
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.1

Haploinsufficiency Scores

• pHI: 0.0671
• hipred: N
• hipred_score: 0.172
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.947

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfp408
• Phenotype: immune system phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: znf408
• Affected structure: ocular blood vessel
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;identical protein binding;metal ion binding