NHLH1
protein-codingnescient helix-loop-helix 1, the group of Basic helix-loop-helix proteins
Gene summary
The helix-loop-helix (HLH) proteins are a family of putative transcription factors, some of which have been shown to play an important role in growth and development of a wide variety of tissues and species. Four members of this family have been clearly implicated in tumorigenesis via their involvement in chromosomal translocations in lymphoid tumors: MYC (MIM 190080), LYL1 (MIM 151440), E2A (MIM 147141), and SCL (MIM 187040).[supplied by OMIM, Nov 2002]
- HEN1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NHLH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005598.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 15 | 0 | 0 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005589.1 | 1 | MANE Select | |
| Ensembl | ENSP00000302189.5 | 1 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- central nervous system development
- cell differentiation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein dimerization activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302101
- Coding exons
- 1
- Length
- 5782
- Individuals with no LoFs
- 120825
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 120827
- p
- 0.00000828
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.04 | 71 | 100 | 0.708 | 0.00000804 | 824 |
| Missense (PolyPhen) | 16 | 29.58 | 0.54091 | 196 | ||
| Synonymous | 0.0858 | 46 | 46.7 | 0.984 | 0.00000353 | 311 |
| Loss of Function | 1.23 | 1 | 3.48 | 0.287 | 2.80e-7 | 31 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000094 | 0.0000093 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.;
Recessive Scores
- pRec
- 0.203
Intolerance Scores
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |