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3 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NHSL2
NHS like 2
Chromosome X · Xq13.1
NCBI Gene: 340527Ensembl: ENSG00000204131.11HGNC: HGNC:33737UniProt: A0A0J9YY72
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcell differentiationspinocerebellar ataxia type 1glycoprotein storage diseaseimmunodeficiency 75hemoglobin H disease
✦AI Summary

NHSL2 (NHS like 2) is an X-linked gene belonging to a protein family that includes NHS and NHSL1, characterized by functional WAVE homology domains 1. As a member of this family, NHSL2 is predicted to function in protein binding and cell differentiation processes. NHSL2 has been identified as a component of competing endogenous RNA (ceRNA) networks involved in Alzheimer's disease pathology, where it was dysregulated in the hippocampus of 5×FAD mice alongside alterations in circRNA-miRNA interactions affecting neuronal development and synaptic function 2. Additionally, NHSL2 expression is significantly altered in bone marrow stem cells (BMSCs) from adolescent idiopathic scoliosis (AIS) patients with osteopenia, where reduced NHSL2 levels correlate with impaired autophagy activity and abnormal BMSC differentiation, leading to decreased osteogenic capacity and increased adipogenic differentiation 3. These findings suggest NHSL2 plays roles in regulating cell differentiation and potentially autophagy-dependent processes. However, the specific molecular mechanisms by which NHSL2 functions in these contexts remain to be elucidated, and direct functional studies of NHSL2 itself are lacking in the provided literature.

Sources cited
1
NHSL2 is part of a protein family (NHS, NHSL1, NHSL2) with functional WAVE homology domains involved in actin remodeling and cell morphology
PMID: 20332100
2
NHSL2 is dysregulated in the hippocampus of 5×FAD Alzheimer's disease mice and participates in circRNA-miRNA-mRNA ceRNA networks affecting neuronal development
PMID: 36466608
3
NHSL2 expression is altered in bone marrow stem cells from AIS-related osteopenia patients with impaired autophagy activity and abnormal osteogenic/adipogenic differentiation
PMID: 36728938
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
spinocerebellar ataxia type 1Open Targets
0.11Weak
glycoprotein storage diseaseOpen Targets
0.03Suggestive
immunodeficiency 75Open Targets
0.03Suggestive
hemoglobin H diseaseOpen Targets
0.03Suggestive
dominant beta-thalassemiaOpen Targets
0.03Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.03Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.03Suggestive
autoinflammation with episodic fever and lymphadenopathyOpen Targets
0.03Suggestive
combined immunodeficiency due to OX40 deficiencyOpen Targets
0.03Suggestive
Hyperlipoproteinemia type 1Open Targets
0.03Suggestive
acute erythroleukemiaOpen Targets
0.03Suggestive
erythroleukemia, familial, susceptibility toOpen Targets
0.03Suggestive
Mast Cell SarcomaOpen Targets
0.03Suggestive
metastatic melanomaOpen Targets
0.01Suggestive
papillary thyroid carcinomaOpen Targets
0.01Suggestive
chronic myelogenous leukemiaOpen Targets
0.00Suggestive
meningococcal infectionOpen Targets
0.00Suggestive
HIV-1 infectionOpen Targets
0.00Suggestive
rheumatoid arthritisOpen Targets
0.00Suggestive
Neurodevelopmental delayOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ANXA13Shared pathway100%ELF1Shared pathway100%ELF2Shared pathway100%ELF5Shared pathway100%ELK3Shared pathway100%ELK4Shared pathway100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
73%
Lung
18%
Ovary
9%
Brain
7%
Liver
3%
Gene Interaction Network
Click a node to explore
NHSL2ANXA13ELF1ELF2ELF5ELK3ELK4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q5HYW2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.51 [0.37–0.70]
RankingsWhere NHSL2 stands among ~20K protein-coding genes
  • #14,478of 20,598
    Most Researched19
  • #5,301of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedNHSL2
Sources retrieved3 papers
Response time—
📄 Sources
3
1
Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer's disease in a 5 × FAD mouse model.
PMID: 36466608
Front Aging Neurosci · 2022
1.00
2
Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia.
PMID: 36728938
Chin Med J (Engl) · 2023
0.67
3
The Nance-Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology.
PMID: 20332100
Hum Mol Genet · 2010
0.33