ZNFX1

zinc finger NFX1-type containing 1, the group of UPF1 like RNA helicases

Basic information

Region (hg38): 20:49237945-49278426

Links

ENSG00000124201 ∙ NCBI:57169 ∙ OMIM:618931 ∙ HGNC:29271 ∙ Uniprot:Q9P2E3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 91 and hyperinflammation (Moderate), mode of inheritance: AR
• immunodeficiency 91 and hyperinflammation (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 91 and hyperinflammation	AR	Allergy/Immunology/Infectious	Among other manifestations, the condition may include immunodeficiency and increased risk of infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described	Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Neurologic	33872655; 33876776

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNFX1 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNFX1 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				8	3	11
missense			108	8	4	120
nonsense	2					2
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	1		2
non coding			5		5	10
Total	2	1	117	16	12

Variants in ZNFX1

This is a list of pathogenic ClinVar variants found in the ZNFX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-49238966-C-T		not specified	Uncertain significance (Dec 30, 2023)
20-49239240-A-C		not specified	Uncertain significance (Oct 26, 2021)
20-49239293-G-A		not specified	Uncertain significance (Dec 12, 2023)
20-49241753-G-A		not specified	Benign (Jan 24, 2024)
20-49241901-G-A		not specified	Uncertain significance (Dec 06, 2021)
20-49242203-C-T		not specified	Uncertain significance (Nov 07, 2022)
20-49242638-C-T		not specified	Uncertain significance (Nov 30, 2022)
20-49243652-A-C		not specified	Uncertain significance (Jan 30, 2024)
20-49243675-C-G		not specified	Uncertain significance (May 01, 2023)
20-49243678-G-A		not specified	Uncertain significance (Apr 22, 2024)
20-49247282-G-C		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
20-49247319-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
20-49247332-G-A		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
20-49247452-C-T		Inborn genetic diseases	Likely benign (Oct 13, 2023)
20-49247472-T-C		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
20-49247475-C-T		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
20-49247545-T-C		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
20-49247609-A-C		Inborn genetic diseases	Uncertain significance (Jul 26, 2021)
20-49247628-CA-C			Uncertain significance (Oct 01, 2019)
20-49247654-ACTATAGAC-A		ZNFX1-related disorder	Uncertain significance (Jan 03, 2022)
20-49247674-T-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
20-49247675-GCTAT-G			Uncertain significance (Feb 28, 2022)
20-49247676-C-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
20-49247697-G-A		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
20-49247709-C-T		Inborn genetic diseases	Uncertain significance (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNFX1	protein_coding	protein_coding	ENST00000396105	13	40481

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000175	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.56	823	1.06e+3	0.778	0.0000607	12695
Missense in Polyphen		206	384.65	0.53555		4666
Synonymous	-0.545	407	393	1.03	0.0000208	3670
Loss of Function	7.06	13	82.0	0.159	0.00000489	922

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000306	0.0000306
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000163	0.000163
Finnish	0.000277	0.000231
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.0331
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.22

Haploinsufficiency Scores

• pHI: 0.216
• hipred: Y
• hipred_score: 0.639
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Znfx1

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;chromatin silencing at centromere;chromatin silencing by small RNA
• Cellular component: chromosome, centromeric region;nucleus;nuclear RNA-directed RNA polymerase complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA binding;zinc ion binding