ZNF408

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

Basic information

Region (hg38): 11:46701030-46705912

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 (541 variants)
Inborn_genetic_diseases (88 variants)
Retinal_dystrophy (35 variants)
Exudative_vitreoretinopathy_6 (11 variants)
Retinitis_pigmentosa_72 (9 variants)
ZNF408-related_disorder (9 variants)
not_specified (6 variants)
Exudative_vitreoretinopathy_1 (5 variants)
Optic_atrophy (2 variants)
Familial_exudative_vitreoretinopathy (2 variants)
Autosomal_recessive_retinitis_pigmentosa (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. These statistics are base on transcript: NM_000024741.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	140 clinvar	6 clinvar	151
missense	1 clinvar	3 clinvar	355 clinvar	13 clinvar	2 clinvar	374
nonsense	1 clinvar	3 clinvar	11 clinvar			15
start loss			1			1
frameshift	1 clinvar	2 clinvar	19 clinvar			22
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	3 clinvar			6
Total	5	9	394	153	8

Highest pathogenic variant AF is 0.000027281847

Loading clinvar variants...

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