ZNF341

Summary

ZNF341 (zinc finger protein 341, HGNC:15992) is a protein-coding gene on chromosome 20q11.22, encoding Zinc finger protein 341 (Q9BYN7). Transcriptional activator of STAT3 involved in the regulation of immune homeostasis.

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 hyper IgE recurrent infection syndrome 3.

Source: NCBI Gene 84905 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyper-IgE recurrent infection syndrome 3, autosomal recessive (Definitive, ClinGen)
• GWAS associations: 8
• Clinical variants (ClinVar): 696 total — 25 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 31
• MANE Select transcript: NM_001282933

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15992
Approved symbol	ZNF341
Name	zinc finger protein 341
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	dJ553F4.3
Ensembl gene	ENSG00000131061
Ensembl biotype	protein_coding
OMIM	618269
Entrez	84905

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000342427, ENST00000375200, ENST00000483118, ENST00000493497, ENST00000497876, ENST00000698694, ENST00000698695, ENST00000874206, ENST00000912308, ENST00000912309, ENST00000912310, ENST00000966829, ENST00000966830

RefSeq mRNA: 3 — MANE Select: NM_001282933 NM_001282933, NM_001282935, NM_032819

CCDS: CCDS13227, CCDS74719

Canonical transcript exons

ENST00000375200 — 15 exons

Exon	Start	End
ENSE00003473933	33770084	33770292
ENSE00003484162	33753172	33753423
ENSE00003508354	33783732	33783864
ENSE00003515778	33788863	33788974
ENSE00003561415	33761862	33762055
ENSE00003587029	33758716	33758806
ENSE00003590321	33781291	33781387
ENSE00003599714	33790988	33792269
ENSE00003636082	33789518	33789588
ENSE00003661026	33766851	33767041
ENSE00003682436	33757148	33757343
ENSE00003889281	33740902	33741012
ENSE00003892076	33748923	33749072
ENSE00003892679	33745103	33745299
ENSE00003974442	33731996	33732052

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 84.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9798 / max 43.1749, expressed in 1620 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184175	3.9798	1620

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.26	gold quality
mucosa of transverse colon	UBERON:0004991	77.63	gold quality
lower esophagus mucosa	UBERON:0035834	77.59	gold quality
granulocyte	CL:0000094	76.52	gold quality
apex of heart	UBERON:0002098	75.51	gold quality
cortical plate	UBERON:0005343	75.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.68	silver quality
buccal mucosa cell	CL:0002336	73.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.73	gold quality
blood	UBERON:0000178	73.56	gold quality
gastrocnemius	UBERON:0001388	73.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.91	gold quality
right frontal lobe	UBERON:0002810	72.70	gold quality
muscle of leg	UBERON:0001383	72.57	gold quality
leukocyte	CL:0000738	72.53	gold quality
monocyte	CL:0000576	72.30	gold quality
prefrontal cortex	UBERON:0000451	72.13	gold quality
cerebellar hemisphere	UBERON:0002245	72.10	gold quality
stromal cell of endometrium	CL:0002255	72.08	gold quality
pancreatic ductal cell	CL:0002079	72.03	silver quality
cerebellar cortex	UBERON:0002129	72.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.41	gold quality
esophagus mucosa	UBERON:0002469	71.32	gold quality
spleen	UBERON:0002106	71.28	gold quality
primary visual cortex	UBERON:0002436	71.27	gold quality
cerebellum	UBERON:0002037	70.86	gold quality
esophagus	UBERON:0001043	70.58	gold quality
lower esophagus	UBERON:0013473	70.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.49	gold quality
ganglionic eminence	UBERON:0004023	70.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.87

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1655.1	ZNF341	Factors with multiple dispersed zinc fingers
MA1655.2	ZNF341	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:29907691

miRNA regulators (miRDB)

43 targeting ZNF341, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4650-5P	99.98	64.69	999
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-3919	99.87	69.45	2489
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-423-5P	98.69	67.48	1522

Literature-anchored findings (GeneRIF, showing 5)

• Study reports two distinct homozygous nonsense mutations in exons 6 and 8 of ZNF341 in four consanguineous families with recurrent bacterial and fungal infections. ZNF341 mutations segregate with a phenotype resembling hyper-immunoglobulin E syndrome. Authors describe ZNF341 as a positive regulator of STAT3 expression and report the clinical and laboratory phenotype of individuals lacking ZNF341. (PMID:29907690)
• Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3. (PMID:29907691)
• Hyper IgE Syndrome in an Isolated Population in Israel. (PMID:35185921)
• Increased radiosensitivity and impaired DNA repair in patients with STAT3-LOF and ZNF341 deficiency, potentially contributing to malignant transformations. (PMID:35511492)
• Inherited human ZNF341 deficiency. (PMID:37080116)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf341	ENSDARG00000103725
mus_musculus	Zfp341	ENSMUSG00000059842
rattus_norvegicus	Zfp341	ENSRNOG00000017086
drosophila_melanogaster	nom	FBGN0037617
drosophila_melanogaster	ouib	FBGN0037618
drosophila_melanogaster	CG8159	FBGN0037619
drosophila_melanogaster	ranshi	FBGN0037620
drosophila_melanogaster	M1BP	FBGN0037621
drosophila_melanogaster	CG1792	FBGN0039860

Protein

Protein identifiers

Zinc finger protein 341 — Q9BYN7 (reviewed: Q9BYN7)

All UniProt accessions (5): Q9BYN7, A0A8V8TML2, A0A8V8TNW4, E9PN62, E9PQQ0

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator of STAT3 involved in the regulation of immune homeostasis. Also able to activate STAT1 transcription.

Subunit / interactions. Binds DNA and to the STAT3 promoter.

Subcellular location. Nucleus.

Disease relevance. Hyper-IgE syndrome 3, autosomal recessive, with recurrent infections (HIES3) [MIM:618282] An immunologic disorder characterized by skin bacterial infections in particular with Staphylococcus aureus, susceptibility to fungal infections such as chronic mucocutaneous candidiasis, atopic dermatitis, recurrent respiratory infections, bronchiectasis, and increased serum IgE and IgG. Immunologic work-up shows impaired differentiation of CD4+ T cells into T-helper 17 cells, decreased memory B cells, and often decreased NK cells. Some patients manifest extrahemapoietic features, including facial dysmorphism, abnormal dentition, alopecia, joint hypermobility and bone fractures. Disease onset is in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYN7-1	1	yes
Q9BYN7-2	2

RefSeq proteins (3): NP_001269862, NP_001269864, NP_116208 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13912

UniProt features (26 total): zinc finger region 12, sequence variant 4, region of interest 3, compositionally biased region 3, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYN7-F1	57.11	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): SP3_Q3, WANG_LMO4_TARGETS_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, chr20q11, AP2_Q6, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, YRCCAKNNGNCGC_UNKNOWN, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ATF6_TARGET_GENES, CBX5_TARGET_GENES, F10_TARGET_GENES, MEF2D_TARGET_GENES, SNRNP70_TARGET_GENES, ZNF2_TARGET_GENES

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), DNA binding (GO:0003677), zinc ion binding (GO:0008270), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
transition metal ion binding	1
transcription regulator activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF341	PGM3	O95394	612
ZNF341	DOCK8	Q8NF50	609
ZNF341	PXMP4	Q9Y6I8	521
ZNF341	IL6ST	P40189	471
ZNF341	AIRE	O43918	448
ZNF341	ERBIN	Q96RT1	418
ZNF341	SPAG4	Q9NPE6	411
ZNF341	GMEB2	Q9UKD1	408
ZNF341	CARD11	Q9BXL7	405
ZNF341	RNF225	M0QZC1	402
ZNF341	STAT3	P40763	388
ZNF341	SPINK5	Q9NQ38	381
ZNF341	BLCAP	P62952	374
ZNF341	ZFAND3	Q9H8U3	369
ZNF341	CTNNBL1	Q8WYA6	366

IntAct

40 interactions, top by confidence:

A	B	Type	Score
MAGEB4	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
CENPP	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
ZNF341	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
ZNF341	CSTF2	psi-mi:“MI:0915”(physical association)	0.560
ZNF341	KLHL38	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
PTK6	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
EMD	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
ZNF341	C11orf68	psi-mi:“MI:0915”(physical association)	0.560
NCK2	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
GRB2	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
ZNF341	ALDH1B1	psi-mi:“MI:0915”(physical association)	0.400
ZNF341	SMARCC2	psi-mi:“MI:0915”(physical association)	0.400
ZNF341	H1-5	psi-mi:“MI:0915”(physical association)	0.400
ZNF341	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.370
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): ZNF341 (Two-hybrid), ZNF341 (Two-hybrid), ZNF341 (Two-hybrid), KLHL38 (Two-hybrid), CENPP (Two-hybrid), ZNF341 (Two-hybrid), ZNF341 (Two-hybrid), ZNF341 (Two-hybrid), ZNF341 (Two-hybrid), ZNF341 (Two-hybrid), C11orf68 (Two-hybrid), GRB2 (Two-hybrid), ZNF341 (Proximity Label-MS), ZNF341 (Proximity Label-MS), ZNF341 (Proximity Label-MS)

ESM2 similar proteins: A0JPB4, A0PJY2, B0K011, O08876, O15090, O57415, O62651, O70237, O75626, O95863, P19544, P22561, P41183, P49952, P55878, P86413, Q02085, Q08DS3, Q0IHB8, Q0P4W9, Q0VDQ9, Q25C93, Q28G88, Q2TAR3, Q2VWH6, Q32NK7, Q3MHQ4, Q3T135, Q3UH06, Q567J8, Q5T0B9, Q5VTD9, Q5XJQ7, Q60636, Q62255, Q66JF8, Q6AY34, Q6DBW0, Q6NRM0, Q804Q5

Diamond homologs: A1L2U9, B0Y9W4, B1WAZ8, B1WBU4, E9PZZ1, J9VE33, O35615, O77027, P34694, P39933, P53968, Q02027, Q0IH98, Q0VCJ6, Q10RP4, Q22678, Q2I689, Q4WJ81, Q59RR0, Q59SN6, Q5SVQ8, Q6P882, Q811F1, Q84MZ4, Q8IVC4, Q8IX07, Q96BR9, Q9BYN7, Q9H4Q3, Q9I9K0, Q9UM63, Q9UTS5, B0K011, P23803, P41995, P60319, P86413, Q08DS3, Q0IHB8, Q32NK7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	ZNF341	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

696 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	10
Uncertain significance	312
Likely benign	304
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1443706	NM_001282933.2(ZNF341):c.1775dup (p.Arg593fs)	Pathogenic
1455938	NM_001282933.2(ZNF341):c.800del (p.Gly267fs)	Pathogenic
1455945	NM_001282933.2(ZNF341):c.1745_1746del (p.Arg582fs)	Pathogenic
2076625	NM_001282933.2(ZNF341):c.468_469dup (p.Gln157fs)	Pathogenic
2109712	NM_001282933.2(ZNF341):c.1921_1922del (p.Met641fs)	Pathogenic
2427074	NC_000020.10:g.(?32371518)(32371690_?)del	Pathogenic
2427075	NC_000020.10:g.(?32340958)(32346632_?)del	Pathogenic
2732393	NM_001282933.2(ZNF341):c.92del (p.Pro31fs)	Pathogenic
3248356	NC_000020.10:g.(?32319828)(32379323_?)del	Pathogenic
3248357	NC_000020.10:g.(?32369077)(32369213_?)del	Pathogenic
3248358	NC_000020.10:g.(?32354637)(32354867_?)del	Pathogenic
3606413	NM_001282933.2(ZNF341):c.419_422dup (p.Met142fs)	Pathogenic
3678447	NM_001282933.2(ZNF341):c.642del (p.Asn215fs)	Pathogenic
4690653	NM_001282933.2(ZNF341):c.1174C>T (p.Gln392Ter)	Pathogenic
4711942	NM_001282933.2(ZNF341):c.1882G>T (p.Glu628Ter)	Pathogenic
4716623	NM_001282933.2(ZNF341):c.720del (p.Met240fs)	Pathogenic
4717807	NM_001282933.2(ZNF341):c.1253del (p.Gln418fs)	Pathogenic
4730355	NM_001282933.2(ZNF341):c.1350C>A (p.Cys450Ter)	Pathogenic
4765929	NM_001282933.2(ZNF341):c.400del (p.Ile134fs)	Pathogenic
4781151	NM_001282933.2(ZNF341):c.1024C>T (p.Arg342Ter)	Pathogenic
599410	NM_001282933.2(ZNF341):c.904C>T (p.Arg302Ter)	Pathogenic
599411	NM_001282933.2(ZNF341):c.1156C>T (p.Arg386Ter)	Pathogenic
599412	NM_001282933.2(ZNF341):c.1083del (p.Lys362fs)	Pathogenic
599413	NM_001282933.2(ZNF341):c.1647C>G (p.Tyr549Ter)	Pathogenic
599414	NM_001282933.2(ZNF341):c.583C>T (p.Gln195Ter)	Pathogenic
1339529	NM_001282933.2(ZNF341):c.1054T>C (p.Cys352Arg)	Likely pathogenic
1678042	NM_001282933.2(ZNF341):c.1622+1G>A	Likely pathogenic
2181175	NM_001282933.2(ZNF341):c.918T>G (p.Gly306=)	Likely pathogenic
2427076	NC_000020.10:g.(?32332889)(32336898_?)dup	Likely pathogenic
2771573	NM_001282933.2(ZNF341):c.1852+1G>A	Likely pathogenic

SpliceAI

2522 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33740900:A:AG	acceptor_gain	1.0000
20:33740901:G:GG	acceptor_gain	1.0000
20:33745056:A:AG	acceptor_gain	1.0000
20:33745067:T:TA	acceptor_gain	1.0000
20:33745089:G:A	acceptor_gain	1.0000
20:33745126:G:A	acceptor_gain	1.0000
20:33749070:CAGG:C	donor_loss	1.0000
20:33749071:AGGT:A	donor_loss	1.0000
20:33749072:GGTA:G	donor_loss	1.0000
20:33749074:T:G	donor_loss	1.0000
20:33766846:CACA:C	acceptor_loss	1.0000
20:33766848:CA:C	acceptor_loss	1.0000
20:33766849:A:AG	acceptor_gain	1.0000
20:33766849:A:C	acceptor_loss	1.0000
20:33766849:AG:A	acceptor_gain	1.0000
20:33766849:AGG:A	acceptor_gain	1.0000
20:33766850:G:GG	acceptor_gain	1.0000
20:33766850:GG:G	acceptor_gain	1.0000
20:33766850:GGG:G	acceptor_gain	1.0000
20:33766850:GGGT:G	acceptor_gain	1.0000
20:33766850:GGGTT:G	acceptor_gain	1.0000
20:33767038:GCAG:G	donor_gain	1.0000
20:33767042:GTA:G	donor_loss	1.0000
20:33770289:ACAA:A	donor_gain	1.0000
20:33770290:CAA:C	donor_gain	1.0000
20:33770291:AA:A	donor_gain	1.0000
20:33770292:AG:A	donor_loss	1.0000
20:33770293:G:GG	donor_gain	1.0000
20:33770293:GT:G	donor_loss	1.0000
20:33783726:TCCCA:T	acceptor_loss	1.0000

AlphaMissense

5580 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33745123:T:C	C55R	1.000
20:33745132:T:C	C58R	1.000
20:33745144:T:C	F62L	1.000
20:33745146:C:A	F62L	1.000
20:33745146:C:G	F62L	1.000
20:33745163:T:C	F68S	1.000
20:33758748:T:A	C324S	1.000
20:33758748:T:C	C324R	1.000
20:33758749:G:C	C324S	1.000
20:33758750:C:G	C324W	1.000
20:33758757:T:A	C327S	1.000
20:33758757:T:C	C327R	1.000
20:33758758:G:A	C327Y	1.000
20:33758758:G:C	C327S	1.000
20:33758758:G:T	C327F	1.000
20:33758759:T:G	C327W	1.000
20:33758769:T:C	F331L	1.000
20:33758770:T:C	F331S	1.000
20:33758771:C:A	F331L	1.000
20:33758771:C:G	F331L	1.000
20:33758788:T:C	L337P	1.000
20:33758796:C:A	H340N	1.000
20:33758796:C:G	H340D	1.000
20:33758797:A:C	H340P	1.000
20:33758797:A:G	H340R	1.000
20:33758798:C:A	H340Q	1.000
20:33758798:C:G	H340Q	1.000
20:33758803:G:C	R342P	1.000
20:33761863:C:A	H344N	1.000
20:33761863:C:G	H344D	1.000

dbSNP variants (sampled 300 via entrez): RS1000055059 (20:33740438 G>C), RS1000133111 (20:33791782 G>A), RS1000294859 (20:33752629 G>A), RS1000319257 (20:33752088 C>G,T), RS1000525252 (20:33757729 C>G), RS1000536513 (20:33747034 C>T), RS1000551864 (20:33765435 A>G), RS1000599729 (20:33776919 C>T), RS1000631632 (20:33733888 G>C), RS1000633904 (20:33751349 G>T), RS1000712823 (20:33783967 C>A,T), RS1000736400 (20:33740248 C>G), RS1000832915 (20:33758811 A>C), RS1000858053 (20:33779137 G>A), RS1000919104 (20:33733693 T>A)

Disease associations

OMIM: gene MIM:618269 | disease phenotypes: MIM:618282, MIM:146840, MIM:147060

GenCC curated gene-disease

Disease	Classification	Inheritance
hyper-IgE recurrent infection syndrome 3, autosomal recessive	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hyper-IgE recurrent infection syndrome 3, autosomal recessive	Definitive	AR

Mondo (3): hyper-IgE recurrent infection syndrome 3, autosomal recessive (MONDO:0032654), long QT syndrome (MONDO:0002442), hyper-IgE recurrent infection syndrome 1, autosomal dominant (MONDO:0007818)

Orphanet (2): Autosomal recessive hyper-IgE syndrome due to ZNF341 deficiency (Orphanet:641368), Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency (Orphanet:2314)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000347	Micrognathia
HP:0000403	Recurrent otitis media
HP:0000445	Wide nose
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000989	Pruritus
HP:0001047	Atopic dermatitis
HP:0001256	Mild intellectual disability
HP:0001382	Joint hypermobility
HP:0001581	Recurrent skin infections
HP:0001596	Alopecia
HP:0001631	Atrial septal defect
HP:0001642	Pulmonic stenosis
HP:0001880	Increased total eosinophil count
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002728	Chronic mucocutaneous candidiasis
HP:0002754	Osteomyelitis
HP:0003212	Increased circulating IgE concentration
HP:0003416	Spinal canal stenosis
HP:0006532	Recurrent pneumonia
HP:0009098	Chronic oral candidiasis
HP:0011108	Recurrent sinusitis
HP:0025616	Sterile abscess
HP:0031292	Cutaneous abscess

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000817_29	Height	6.000000e-22
GCST008152_58	Weight	1.000000e-06
GCST008163_321	Height	6.000000e-11
GCST012227_1371	Hip circumference adjusted for BMI	2.000000e-08
GCST012227_1372	Hip circumference adjusted for BMI	3.000000e-13
GCST90020028_1621	Hip circumference adjusted for BMI	3.000000e-10
GCST90020028_1622	Hip circumference adjusted for BMI	7.000000e-16
GCST90020028_1623	Hip circumference adjusted for BMI	6.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C567925	Hyper-Ige Recurrent Infection Syndrome, Autosomal Dominant (supp.)
C564135	Immunodeficiency with Defective Leukocyte and Lymphocyte Function and with Response to Histamine-1 Antagonist (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Tobacco Smoke Pollution	increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, decreases expression	1
Cannabidiol	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Urethane	increases expression	1
Zinc	increases expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_HD22	HEK293 eGFP-ZNF341	Transformed cell line	Female

Clinical trials (associated diseases)

74 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00033982	PHASE3	COMPLETED	Posaconazole to Treat Invasive Fungal Infections
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00527878	PHASE2	TERMINATED	Effect of Ranitidine on Hyper-IgE Recurrent Infection (Job’s) Syndrome
NCT02996448	PHASE2	TERMINATED	Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT00001515	PHASE1	COMPLETED	Diagnostic Effectiveness of Virtual Bronchoscopy
NCT00260702	PHASE1	COMPLETED	Omalizumab to Treat Hyper-IgE (Job’s) Syndrome
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval