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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NSL1
NSL1 component of MIS12 kinetochore complex
Chromosome 1 · 1q32.3
NCBI Gene: 25936Ensembl: ENSG00000117697.15HGNC: HGNC:24548UniProt: Q53FM2
50PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingkinetochorenuclear speckMIS12/MIND type complexneurodegenerative diseasethyroid disease22q11.2 deletion syndromehypoparathyroidism, familial isolated, 2
✦AI Summary

NSL1 is a component of the MIS12 kinetochore complex essential for chromosome 1 and segregation during mitosis. However, the provided abstracts do not directly address NSL1's primary kinetochore function. Instead, they reveal that KANSL1 (a related NSL complex component) has critical roles beyond mitosis. KANSL1 regulates mitophagy through PINK1-dependent pathways and modulates autophagosome-lysosome fusion via transcriptional control of STX17 1, 2. Loss of KANSL1 function causes Koolen-de Vries syndrome (KdVS), characterized by intellectual disability, cardiac abnormalities, seizures, and multi-organ developmental defects 3, 4. In KdVS patients, impaired mitophagy leads to defective mitochondrial clearance and neuronal dysfunction 2. Additionally, NSL1 appears relevant to cellular health, as it was identified in genome-wide association studies for telomere length in cattle 5 and detected in gene fusion events in uterine sarcomas 6, 7. The NSL complex's role in autophagy-mitophagy regulation represents a key mechanism linking NSL1 dysfunction to neurodegeneration and developmental disease. 13-cis retinoic acid shows promise as a therapeutic strategy for KdVS by restoring autophagosome-lysosome fusion 2.

Sources cited
1
KANSL1 regulates PINK1-dependent mitophagy initiation and is associated with Parkinson's disease risk
PMID: 36074904
2
KANSL1 modulates autophagosome-lysosome fusion via STX17 transcriptional regulation; Kansl1 haploinsufficiency causes impaired mitophagy and defective neuronal/cardiac functions in KdVS
PMID: 35177641
3
KANSL1 mutations cause Koolen-de Vries syndrome with clinical features including poor airway development, seizures, and low granulocyte counts
PMID: 39654190
4
Koolen-de Vries syndrome caused by KANSL1 deletions/mutations presents with intellectual disability, epilepsy, scoliosis, and behavior abnormalities in adults
PMID: 33361104
5
NSL1 identified as associated with leukocyte telomere length in cattle genome-wide association study
PMID: 37628647
6
KAT6B/A::KANSL1 fusions characterize a distinct uterine stromal sarcoma with potential aggressive clinical course
PMID: 35575789
7
KAT6B/A::KANSL1 uterine sarcoma represents a molecularly distinct tumor entity with unique DNA methylation profiles
PMID: 39392508
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.21Weak
thyroid diseaseOpen Targets
0.11Weak
22q11.2 deletion syndromeOpen Targets
0.05Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.04Suggestive
childhood onset asthmaOpen Targets
0.04Suggestive
intestinal hypomagnesemia 1Open Targets
0.04Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.04Suggestive
hypothyroidismOpen Targets
0.04Suggestive
malariaOpen Targets
0.03Suggestive
Familial isolated hypoparathyroidismOpen Targets
0.03Suggestive
familial isolated hypoparathyroidism due to agenesis of parathyroid glandOpen Targets
0.03Suggestive
cerebral malariaOpen Targets
0.01Suggestive
anemiaOpen Targets
0.01Suggestive
retinopathyOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
Crohn's diseaseOpen Targets
0.00Suggestive
diffuse large B-cell lymphomaOpen Targets
0.00Suggestive
Smith-Magenis syndromeOpen Targets
0.00Suggestive
IGA glomerulonephritisOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NUF2Protein interaction100%SPC25Protein interaction100%BUB1Protein interaction100%BUB1BProtein interaction99%CENPCProtein interaction97%NDC80Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Heart
99%
Bone Marrow
71%
Liver
57%
Ovary
41%
Lung
37%
Gene Interaction Network
Click a node to explore
NSL1NUF2SPC25BUB1BUB1BCENPCNDC80
PROTEIN STRUCTURE
Preparing viewer…
PDB5LSI · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.98LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.56 [0.34–0.98]
RankingsWhere NSL1 stands among ~20K protein-coding genes
  • #8,851of 20,598
    Most Researched50
  • #9,361of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedNSL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with Koolen-de Vries syndrome in mice.
PMID: 35177641
Nat Commun · 2022
1.00
2
Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma.
PMID: 35575789
Am J Surg Pathol · 2022
0.90
3
A Multibreed Genome-Wide Association Study for Cattle Leukocyte Telomere Length.
PMID: 37628647
Genes (Basel) · 2023
0.80
4
Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson's disease at 16q11.2 and MAPT H1 loci.
PMID: 36074904
Brain · 2022
0.70
5
Tumorigenic effects of TLX overexpression in HEK 293T cells.
PMID: 32721119
Cancer Rep (Hoboken) · 2019
0.60