HCLS1
protein-codinghematopoietic cell-specific Lyn substrate 1
Gene summary
Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; protein kinase binding activity; and signaling adaptor activity. Involved in several processes, including granulocyte colony-stimulating factor signaling pathway; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; and positive regulation of protein import into nucleus. Located in cytosol; nucleus; and plasma membrane. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.5 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 HCLS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005335.6. 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 | 1 | 1 | ||||
| missense | 78 | 6 | 84 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 81 | 7 | 0 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005326.3 | 13 | MANE Select | |
| Ensembl | ENSP00000320176.3 | 13 | MANE Select | |
| RefSeq | NP_001278970.2 | 12 | Standard | |
| Ensembl | ENSP00000387645.2 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Bacterial invasion of epithelial cells - Homo sapiens (human)
- Shigellosis - Homo sapiens (human)
- Pathogenic Escherichia coli infection - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- regulation of transcription, DNA-templated
- positive regulation of cell population proliferation
- response to hormone
- positive regulation of phosphatidylinositol 3-kinase signaling
Molecular Function
- RNA polymerase II transcription factor binding
- actin binding
- protein binding
- SH3 domain binding
- protein kinase binding
Cellular Component
- nucleus
- transcription factor complex
- cytoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314583
- Coding exons
- 13
- Length
- 29529
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 49
- Defined
- 125748
- p
- 0.000195
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0535 | 283 | 280 | 1.01 | 0.0000159 | 3157 |
| Missense (PolyPhen) | 27 | 31.234 | 0.86444 | 288 | ||
| Synonymous | 0.467 | 103 | 109 | 0.943 | 0.00000695 | 928 |
| Loss of Function | 2.72 | 15 | 31.5 | 0.476 | 0.00000180 | 346 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression.;
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- LoFtool
- 0.790
- RVIS EVS
- 0.54
- RVIS percentile EVS
- 81.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.901
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |