Unc13d
- Known as:
- Unc13d
- Catalog number:
- 045899A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Unc13d
Related genes to: Unc13d
- Gene:
- UNC13D NIH gene
- Name:
- unc-13 homolog D
- Previous symbol:
- -
- Synonyms:
- Munc13-4
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-10-16
- Date modifiied:
- 2019-04-23
Related products to: Unc13d
Related articles to: Unc13d
- The UNC13D gene encodes Munc13-4, a key regulator of cytotoxic granule exocytosis in effector immune cells, enabling the release of perforin and granzymes that are essential for cytotoxic function and immune surveillance. Loss-of-function mutations in UNC13D result in immune dysregulation syndromes, most notably familial hemophagocytic lymphohistiocytosis (fHLH, also referred to as FHL). This review provides a comprehensive overview of UNC13D, including its structural characteristics, biological functions, and spectrum of pathogenic variants. We summarize the mechanistic roles of Munc13-4 in granule-mediated cytotoxicity and examine the clinical correlations between UNC13D mutations and fHLH type 3 (FHL3). Furthermore, we discuss emerging evidence linking UNC13D dysfunction to a broader range of diseases, highlighting its clinical relevance and potential as both a diagnostic biomarker and therapeutic target. Overall, this review aims to bridge the gap between molecular mechanisms and clinical translation in UNC13D-related disorders. - Source: PubMed
Wang ZiqianChen ChongDuan ZhaojunWei ChongZhang WeiLuo YunpingZhou Daobin - Primary hemophagocytic lymphohistiocytosis is mainly caused by biallelic variants in genes disrupting cytotoxic NK- and T-cell function (PRF1, UNC13D, STX11, STXBP2, RAB27A, and LYST). A "pathway defect accumulation" model proposes that heterozygous variants in multiple FHL genes (digenic or multigenic inheritance) may increase susceptibility, but its significance remains debated. We assessed the prevalence and clinical relevance of di-/multigenic FHL genotypes in a German FHL cohort (1987-2023) and the UK Biobank (UKB, 469,589 participants). We analyzed (i) variants classified as disease mutations in the Human Gene Mutation Database (HGMD), (ii) common variants such as PRF1 p.Ala91Val and p.Asn252Ser as well as (iii) additional variants previously reported in digenic HLH and explored phenotypic associations using ICD-10 codes for possible HLH-related conditions. In the German cohort, among 635 individuals sequenced for more than one FHL gene, no symptomatic patient with abnormal NK/CTL-degranulation carried digenic/multigenic heterozygous variants. In UKB, 575 individuals carried digenic FHL genotypes (0.1% prevalence), without enrichment for HLH-associated phenotypes (OR=0.95; p=1). Four individuals carried trigenic genotypes; none had HLH-related diagnoses. Several HGMD-labeled pathogenic variants were observed biallelically in asymptomatic adults, suggesting potential misclassification. Including PRF1 p.Ala91Val and p.Asn252Ser increased digenic variant carriers to 2,590, but did not cause phenotype enrichment. Digenic heterozygous FHL variants are relatively common in the general population but do not confer increased FHL risk. Many reported pathogenic FHL variants may be benign. These findings argue against classifying multigenic heterozygous carriers as at risk and support integrating population data into variant interpretation. - Source: PubMed
Publication date: 2026/03/31
Borisov OlegMann JasminWalz Kevin KimOyen FlorianLichtenfeld Helena ClaraLehmberg KaiKöttgen AnnaEhl StephanWegehaupt Oliver - Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy, with its pathogenesis closely associated with cellular states at various stages of differentiation. Existing clinical prognostic models often fail to account for this heterogeneity and lack integration of key molecular pathways. This study aimed to characterize AML differentiation-associated heterogeneity at the single-cell level, investigate the role of UNC13D in immune and dedifferentiation states, and develop a prognostic model integrating these features. - Source: PubMed
Publication date: 2026/02/25
Wang ZiqianZhou Daobin - Not available. - Source: PubMed
Publication date: 2026/03/05
Duan YanlongGao HuixiaJin LingYang JingHuang ShuangZhang MengLi NanYang XueliangXu HanliWang Tianyou - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a central nervous system (CNS) inflammatory disease characterized by contrast-enhanced MRI findings of salt-and-pepper-like lesions predominantly affecting the brainstem and cerebellum. We report two patients with CLIPPERS-like brain MRI findings who carried the same missense variant in one allele along with deleterious variants in the opposite allele. Patient 1, a 23-year-old female, presented at 15 years of age with neurological symptoms and an MRI showing spontaneously resolving, contrast-enhancing lesions in the cerebellum. At age 16, the patient experienced an episode with systemic manifestations followed by recurrent CNS lesions that responded to steroid therapy. At age 22, the patient developed punctate to nodular contrast-enhancing lesions in the brainstem, cerebellum, and cerebrum, findings consistent with CLIPPERS. Patient 2, an 18-year-old female, presented at age 11 with ataxia and dysarthria, and an MRI showing multiple contrast-enhancing lesions in the cerebellum and brainstem, consistent with CLIPPERS MRI findings. Cerebellar biopsy revealed perivascular CD4 T-lymphocyte infiltration, and the patient responded to steroid therapy, leading to an initial diagnosis of CLIPPERS. These patients were suspected of having inborn errors of immunity and were identified to have compound heterozygous variants along with downregulated Munc13-4 protein. Both patients underwent allogeneic hematopoietic cell transplantation, with patient 1 remaining neurologically stable for two years post-transplantation, while patient 2 experienced a post-transplant relapse requiring steroid therapy. These cases highlight that biallelic variants in the gene may cause CNS-predominant inflammation that mimics CLIPPERS. - Source: PubMed
Publication date: 2026/03/04
Sagawa HirotakaHirata KoseiKatayama SaoriShibata HirofumiToyofuku EtsushiKaneko ShuyaKatata YuTakezawa YusukeUematsu MitsuguOnishi IichirohYamazaki YutoHattori TakaakiYamamoto MasahideShimizu MasakiImai KohsukeYasumi TakahiroMorio TomohiroYokota TakanoriSasahara YojiKanegane Hirokazu