ZNFX1

protein-coding

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

Gene summary

Enables RNA binding activity. Involved in defense response to bacterium and defense response to virus. Is active in cytoplasmic stress granule. Implicated in immunodeficiency 91. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_021035.3

Inheritance

ClinVar variants

P:12U:262B:36

Top phenotype

Immunodeficiency 91 and hyperinflammation

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr20:49,237,946-49,278,426

External References & Databases

Ensembl (ENSG00000124201)

Transcript & Mutation Effects

hg38 • Region Span ~40.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 91 and hyperinflammationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030491

Submitter: PanelApp Australia

immunodeficiency 91 and hyperinflammationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030491

Submitter: Labcorp Genetics (formerly Invitae)

immunodeficiency 91 and hyperinflammationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030491

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Immunodeficiency 91 and hyperinflammationAR

Manifestation: Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Refs: 33872655; 33876776

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNFX1 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 243

not providedTotal: 34

Immunodeficiency 91 and hyperinflammationTotal: 23

ZNFX1-related disorderTotal: 16

not specifiedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021035.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	21 clinvar		22
missense			252 clinvar	15 clinvar		267
nonsense	4 clinvar	1 clinvar				5
start loss						0
frameshift	4 clinvar	2 clinvar	6 clinvar			12
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	8	4	262	36	0	310

Highest pathogenic variant AF is 0.0000065657296

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021035.3	RefSeq	NP_066363.1	13	MANE Select
ENST00000396105.6	Ensembl	ENSP00000379412.1	13	MANE Select
ENST00000371744.5	Ensembl	ENSP00000360809.1	8	Standard
ENST00000371752.5	Ensembl	ENSP00000360817.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of Telomerase

Biological Process

regulation of transcription by RNA polymerase II
chromatin silencing at centromere
chromatin silencing by small RNA

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
RNA binding
zinc ion binding

Cellular Component

chromosome, centromeric region
nucleus
nuclear RNA-directed RNA polymerase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396105
Coding exons: 13
Length: 40481
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.56	823	1.06e+3	0.778	0.0000607	12695
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000031	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00028	0.00023	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.0331
RVIS EVS: -0.45
RVIS percentile EVS: 24.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.983

Gene Damage Prediction

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