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Cernunnos-XLF deficiency is a rare form of combined immunodeficiency characterized by microcephaly, growth retardation, and T and B cell lymphopenia.
NHEJ1 encodes non-homologous end joining factor 1 (299 aa). DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance. Highest expression in Testis (23.6 TPM) and Cervix Ectocervix (18.7 TPM).
Cernunnos-XLF deficiency is caused by mutations in the NHEJ1 gene on chromosome 2.
The NHEJ1 protein participates in p-T2609,S2612,T2638,T2647-PRKDC:XRCC5:XRCC6:p-S516,S645-DCLRE1C:XRCC4:LIG4:NHEJ1:POLL,POLM:Ligatable DNA DSB ends, p-T2609,S2612,T2638,T2647-PRKDC:XRCC5:XRCC6:p-S516,S645-DCLRE1C:XRCC4:LIG4:NHEJ1:POLL,POLM:Extended ligatable DNA DSB ends, and XRCC4:LIG4, NHEJ1 and POLL or POLM bind DNA DSBs in NHEJ pathways.
NHEJ1 is classified as a druggable target with score 0.0.
Genetic testing for NHEJ1 is available. Testing is considered confirmatory for diagnosis.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for Cernunnos-XLF deficiency.
8 publications have been identified in PubMed for Cernunnos-XLF deficiency. Research spans Review / Meta-Analysis (38%), Basic Science / Preclinical (38%), and Case Report / Case Series (25%).
Rayi A (2026). [PMID: 30725883](https://pubmed.ncbi.nlm.nih.gov/30725883/). *Unknown Journal*. [Review / Meta-Analysis]
Zha S (2026). [PMID: 41871908](https://pubmed.ncbi.nlm.nih.gov/41871908/). *Genes Dev*. [Review / Meta-Analysis]
Kabadayı G (2025). [PMID: 41225329](https://pubmed.ncbi.nlm.nih.gov/41225329/). *BMC immunology*. [Review / Meta-Analysis]
Elbadry MI (2025). [PMID: 40047910](https://pubmed.ncbi.nlm.nih.gov/40047910/). *Annals of hematology*. [Basic Science / Preclinical]
Deng Z (2024). [PMID: 39341501](https://pubmed.ncbi.nlm.nih.gov/39341501/). *The Journal of biological chemistry*. [Basic Science / Preclinical]
Pageault L (2024). [PMID: 39594674](https://pubmed.ncbi.nlm.nih.gov/39594674/). *Cells*. [Basic Science / Preclinical]
Chbihi M (2024). [PMID: 39264509](https://pubmed.ncbi.nlm.nih.gov/39264509/). *Journal of clinical immunology*. [Case Report / Case Series]
Navarro AM (2024). [PMID: 39836852](https://pubmed.ncbi.nlm.nih.gov/39836852/). *Biomedica : revista del Instituto Nacional de Salud*. [Case Report / Case Series]
Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 1:00 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center
Common questions about Cernunnos-XLF deficiency