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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ZNF462
zinc finger protein 462
Chromosome 9 Β· 9q31.2
NCBI Gene: 58499Ensembl: ENSG00000148143.14HGNC: HGNC:21684UniProt: Q96JM2
62PubMed Papers
21Diseases
0Drugs
83Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingnucleoplasmtranscription cis-regulatory region bindingnucleusWeiss-Kruszka syndromecraniosynostosisgenetic disorderneurodegenerative disease
✦AI Summary

ZNF462 is a zinc finger transcription factor located on chromosome 9.2 that functions as a regulator of chr9 structure and transcription 12. In embryonic stem cells, ZNF462 regulates pluripotency and differentiation by controlling expression of SOX2, POU5F1/OCT4, and NANOG, and modulates neuronal development and neural cell differentiation 2. The protein binds PBX1 to prevent its heterodimerization with HOXA9 and subsequent DNA binding. Loss-of-function variants in ZNF462 cause Weiss-Kruszka syndrome (WSKA), an autosomal dominant congenital anomaly disorder with fewer than 40 reported cases 34. WSKA is characterized by developmental delay (79% of patients), distinctive facial features including ptosis (83%), down-slanting palpebral fissures (58%), and metopic ridging or craniosynostosis (33%), along with feeding difficulties, hypotonia, corpus callosum dysgenesis (25%), and cardiac defects (21%) 5. Haploinsufficiency rather than complete loss-of-function appears to drive the phenotype 36. Additionally, ZNF462 variants have been identified as potentially contributing to congenital hypogonadotropic hypogonadism, suggesting broader developmental roles 7. Emerging evidence suggests possible associations with autoimmune disease development, warranting further investigation 3.

Sources cited
1
ZNF462 is a zinc finger nuclear factor involved in transcription by regulating chromatin structure
PMID: 20219459
2
ZNF462 regulates pluripotency and differentiation of embryonic stem cells and neuronal development
PMID: 21570965
3
WSKA caused by ZNF462 variants presents with global developmental delay, hypotonia, feeding difficulties, and craniofacial abnormalities; haploinsufficiency mechanism; possible autoimmune disease association
PMID: 39069253
4
WSKA characterized by metopic ridging, ptosis, corpus callosum abnormalities, cardiac malformations; 32 individuals reported to date
PMID: 39287049
5
Comprehensive phenotype delineation of ZNF462 loss-of-function variants in 24 individuals; developmental delay (79%), autism (33%), characteristic facial features with ptosis (83%), down-slanting palpebral fissures (58%)
PMID: 31361404
6
ZNF462 disruption by translocation causes syndromic intellectual disability and autism with metopic craniosynostosis and corpus callosum dysgenesis
PMID: 29427787
7
ZNF462 gene deletions in 9q31 region cause recognizable phenotype with hearing loss, microcephaly, palate abnormalities, and short stature
PMID: 36461789
8
ZNF462 variants identified as involved in congenital hypogonadotropic hypogonadism development
PMID: 41042998
9
De novo splicing variant in ZNF462 causes WSKA with growth retardation; haploinsufficiency mechanism supported
PMID: 40105472
Disease Associationsβ“˜21
Weiss-Kruszka syndromeOpen Targets
0.80Strong
craniosynostosisOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.53Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
hypothyroidismOpen Targets
0.48Moderate
intellectual disability, autosomal dominantOpen Targets
0.45Moderate
mathematical abilityOpen Targets
0.43Moderate
atrial fibrillationOpen Targets
0.43Moderate
androgenetic alopeciaOpen Targets
0.43Moderate
prostate carcinomaOpen Targets
0.41Moderate
Hereditary breast cancerOpen Targets
0.41Moderate
hereditary breast carcinomaOpen Targets
0.41Moderate
Global developmental delayOpen Targets
0.37Weak
ptosisOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.37Weak
Autistic behaviorOpen Targets
0.37Weak
Prominent metopic ridgeOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.35Weak
lysosomal storage diseaseOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.35Weak
Weiss-Kruszka syndromeUniProt
Pathogenic Variants83
NM_021224.6(ZNF462):c.3305dup (p.Gln1103fs)Pathogenic
Inborn genetic diseases|Weiss-Kruszka syndrome|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1103
NM_021224.6(ZNF462):c.4609C>T (p.Arg1537Ter)Pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1537
NM_021224.6(ZNF462):c.3700C>T (p.Arg1234Ter)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 1234
NM_021224.6(ZNF462):c.4180del (p.Trp1394fs)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 1394
NM_021224.6(ZNF462):c.3649C>T (p.Arg1217Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 1217
NM_021224.6(ZNF462):c.6832+2T>CPathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025
NM_021224.6(ZNF462):c.3414del (p.Glu1139fs)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1139
NM_021224.6(ZNF462):c.3898C>T (p.Arg1300Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1300
NM_021224.6(ZNF462):c.4460_4463del (p.Thr1487fs)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1487
NM_021224.6(ZNF462):c.4779_4780insC (p.Ile1594fs)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1594
NM_021224.6(ZNF462):c.429del (p.Val144fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 144
NM_021224.6(ZNF462):c.3020del (p.Asn1007fs)Likely pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1007
NM_021224.6(ZNF462):c.1910_1911dup (p.Ser638fs)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 638
NM_021224.6(ZNF462):c.1975C>T (p.Gln659Ter)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 659
NM_021224.6(ZNF462):c.4828C>T (p.Gln1610Ter)Likely pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1610
NM_021224.6(ZNF462):c.5840_5841del (p.Gln1947fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1947
NM_021224.6(ZNF462):c.2987del (p.Arg996fs)Pathogenic
Weiss-Kruszka syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 996
NM_021224.6(ZNF462):c.4891C>T (p.Gln1631Ter)Likely pathogenic
Familial cancer of breast
β˜…β˜†β˜†β˜†2024β†’ Residue 1631
NM_021224.6(ZNF462):c.6696-2A>CPathogenic
Familial cancer of breast
β˜…β˜†β˜†β˜†2024
NM_021224.6(ZNF462):c.1992del (p.Leu665fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 665
View on ClinVar β†—
Related Genes
ASXL2Protein interaction92%VAX1Protein interaction90%
Tissue Expression6 tissues
Ovary
100%
Heart
99%
Brain
58%
Lung
27%
Liver
9%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
ZNF462ASXL2VAX1
PROTEIN STRUCTURE
Preparing viewer…
PDB1X6F Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.08Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.05 [0.03–0.08]
RankingsWhere ZNF462 stands among ~20K protein-coding genes
  • #7,527of 20,598
    Most Researched62
  • #897of 5,498
    Most Pathogenic Variants83 Β· top quartile
  • #24of 17,882
    Most Constrained (LOEUF)0.08 Β· top 1%
Genes detectedZNF462
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 31670927
1.00
2
A novel pathogenic variant in ZNF462 gene associated with Weiss-Kruszka syndrome and systemic lupus erythematosus.
PMID: 36688693
Rheumatology (Oxford) Β· 2023
0.90
3
Phenotypic spectrum in Weiss-Kruszka syndrome caused by ZNF462 variants: Three new patients and literature review.
PMID: 39069253
Eur J Med Genet Β· 2024
0.80
4
Seven Novel Variants of Weiss-Kruszka Syndrome and Phenotype Expansion.
PMID: 39287049
Am J Med Genet A Β· 2025
0.70
5
Phenotype delineation of ZNF462 related syndrome.
PMID: 31361404
Am J Med Genet A Β· 2019
0.60