NHLH2
Helix-loop-helix protein 2
Also known as: bHLHa34, HEN2, HEN2_HUMAN, NSCL2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q02577
- Gene
- NHLH2
- Ensembl
- ENSG00000177551
- Chromosome
- 1
- Canonical length
- 135 aa
- Protein class
- Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Nuclear bodies
- Quaternary structure
- Homodimer
OverviewNCBI Gene
Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within with a positive effect on apoptotic process; hypothalamus gonadotrophin-releasing hormone neuron development; and peripheral nervous system development. Predicted to act upstream of or within several processes, including cell migration in hindbrain; male gonad development; and male mating behavior. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex. Implicated in hypogonadotropic hypogonadism. [provided by Alliance of Genome Resources, Apr 2025]
Canonical amino-acid sequenceUniProt
135 residues, UniProt reviewed canonical sequence.
>Q02577|NHLH2
1 MMLSPDQAAD SDHPSSAHSD PESLGGTDTK VLGSVSDLEP VEEAEGDGKG GSRAALYPHP
61 QQLSREEKRR RRRATAKYRS AHATRERIRV EAFNLAFAEL RKLLPTLPPD KKLSKIEILR
121 LAICYISYLN HVLDVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NHLH2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.59
- Highest tissue expression
- 6.6 nTPM
Expression across tissuesHPA
Tissue
- cerebellum: 6.6 nTPM
- hypothalamus: 6.2 nTPM
- skin: 3.1 nTPM
- midbrain: 3 nTPM
- hippocampal formation: 2.9 nTPM
- spinal cord: 2.6 nTPM
Single-cell type
- thymic myoid cells: 19 nCPM
- breast myoepithelial cells: 11 nCPM
- brain excitatory neurons: 8 nCPM
- ependymal cells: 7.4 nCPM
- esophageal basal cells: 7.4 nCPM
- oligodendrocytes: 7.3 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- pons: 16 nTPM
- thalamus: 14 nTPM
- cerebellum: 13 nTPM
- midbrain: 11 nTPM
- hypothalamus: 8.7 nTPM
- medulla oblongata: 8.6 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NHLH2.
Disease | AllUniProt
Conditions NHLH2 is implicated in, by any mechanism.
- Hypogonadotropic hypogonadism 27 without anosmia (HH27) MIM:619755
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.09
- gnomAD pLI
- 0.58
- gnomAD missense Z
- 1.05
- DepMap mean gene effect
- 0
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- cell migration in hindbrain
- central nervous system development
- hypothalamus gonadotrophin-releasing hormone neuron development
- male gonad development
- male mating behavior
- ovulation cycle
- peripheral nervous system development
- positive regulation of transcription by RNA polymerase II
- regulation of transcription by RNA polymerase II
Molecular functions
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity, RNA polymerase II-specific
- protein dimerization activity
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- sequence-specific double-stranded DNA binding
- transcription coactivator binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NHLH2 as an antibody target. Whether an autoantibody or antibody against NHLH2 could matter depends on whether native NHLH2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NHLH2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label NHLH2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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