ZNF341

protein-coding

zinc finger protein 341, the group of Zinc fingers C2H2-type

Gene summary

Enables DNA binding activity and DNA-binding transcription activator activity. Predicted to be involved in regulation of DNA-templated transcription. Located in nucleus. Implicated in autosomal recessive hyper-IgE syndrome 3 with recurrent infections. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001282933.2

Inheritance

ClinVar variants

P:29U:319B:263

Top phenotype

Hyper-IgE recurrent infection syndrome 3, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr20:33,731,657-33,792,269

External References & Databases

Ensembl (ENSG00000131061)

Transcript & Mutation Effects

hg38 • Region Span ~60.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hyper-IgE recurrent infection syndrome 3, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032654

Submitter: Labcorp Genetics (formerly Invitae)

hyper-IgE recurrent infection syndrome 3, autosomal recessiveDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032654

Submitter: ClinGen

ZNF341 deficiency in relation to Hyper IgE syndrome 3, autosomal recessive, with recurrent infections, was first reported in 2018 (PMID: 29907691 & 29907690). ZNF341 deficiency is associated with high levels of IgE, eczema, atopic dermatitis, chronic mucocutaneous candidiasis, and recurrent pulmonary infections. ZNF341 is a transcription factor that regulates STAT3 expression; patients with ZNF341 deficiency showed decreased expression and STAT3 function in T lymphocytes. Decrease Th17 subsets characterize the immunologic phenotype of ZNF341 deficient patients. Evidence supporting this gene-disease relationship includes case-level data and experimental evidence. This curation included ten probands from 10 unrelated consanguineous families (PMID: 29907691, 29907690 & 37080116). All the alleles are loss of function with experimental data, except for the allele p.Ser64Ter. Experimentally, this gene-disease relationship is supported by its wide expression in immune cells such as B cells, T cells, monocytes, and basophils and its role in regulating STAT3 expression demonstrated by CHIP-Seq and RNAseq in patient´s cells and in vitro cell models. In summary, ZNF341 is definitively associated with Hyper IgE syndrome 3, autosomal recessive, with recurrent infections. This has been repeatedly demonstrated in research and has been upheld over time. This classification was approved by the ClinGen SCID/CID Working Group on DATE (SOP Version 8).

hyper-IgE recurrent infection syndrome 3, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032654

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hyper-IgE recurrent infection syndrome 3, autosomal recessiveAR

Manifestation: Allergy/Immunology/Infectious; Craniofacial; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described with susceptibility to recurrent bacterial and fungal infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial in order to decrease morbidity and mortality

Refs: 29907690; 29907691

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF341 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 620

not specifiedTotal: 231

ZNF341-related disorderTotal: 25

Hyper-IgE recurrent infection syndrome 3, autosomal recessiveTotal: 21

Hyper-IgE recurrent infection syndrome 1, autosomal dominantTotal: 1

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282933.2. 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	4 clinvar	230 clinvar	4 clinvar	239
missense		2 clinvar	305 clinvar	27 clinvar	2 clinvar	336
nonsense	8 clinvar					8
start loss						0
frameshift	12 clinvar	2 clinvar	5 clinvar			19
splice donor/acceptor (+/-2bp)		4 clinvar	5 clinvar			9
Total	20	9	319	257	6	611

Highest pathogenic variant AF is 0.000019153733

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282933.2	RefSeq	NP_001269862.1	15	MANE Select
ENST00000375200.6	Ensembl	ENSP00000364346.1	15	MANE Select
NM_001282935.2	RefSeq	NP_001269864.1	13	Standard
NM_032819.5	RefSeq	NP_116208.3	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
regulation of transcription by RNA polymerase II

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342427
Coding exons: 15
Length: 60613
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	431	528	0.816	0.0000327	5498
Missense (PolyPhen)		105	162.18	0.64743		1889
Synonymous	0.0237	233	233	0.998	0.0000160	1727
Loss of Function	3.25	16	37.5	0.427	0.00000200	425

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00036	0.00036	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;

Recessive Scores

pRec: 0.0932

Intolerance Scores

LoFtool: 0.578
RVIS EVS: -1.14
RVIS percentile EVS: 6.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.804

Gene Damage Prediction

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