STAB1
protein-codingstabilin 1, the group of Scavenger receptors
Gene summary
This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 16 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0958237
Submitter: LiferaOmics
Genetic evidence – Published PMID: 37490907 – Reports bi-allelic STAB1 variants in 10 affected individuals from 7 families with unexplained hyperferritinemia without iron overload. PMID: 37490907 – Family 1– one proband. Case-level (non-LOF start = 0.1; homozygous missense; distant consanguinity) = 0.1; Segregation = 0; Case control = 0 Family 1 total = 0.1 PMID: 37490907 – Family 2 – two affected siblings. Case-level (biallelic predicted null in AR model; homozygous frameshift; distant consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation (affected sibling; both affected with shared genotype; conservative assignment) = 0.5; Case-control = 0 Family 2 total = 1.5 PMID: 37490907 – Family 3 – two affected siblings. Case-level (AR compound heterozygous; one predicted null + one non-LOF missense; each variant evaluated independently; no consanguinity deduction applied) = 1.6; Segregation (affected sibling; conservative assignment) = 0.5; Case-control = 0 Family 3 total = 2.1 PMID: 37490907 – Family 4 – two affected siblings. Case-level (AR compound heterozygous; one predicted null + one non-LOF missense; each variant evaluated independently; no consanguinity deduction applied) = 1.6; Segregation (affected sibling; conservative assignment) = 0.5; Case-control = 0 Family 4 total = 2.1 PMID: 37490907 – Family 5 – one proband. Case-level (AR compound heterozygous; two non-LOF missense each variant evaluated independently; no consanguinity deduction applied) = 0.2; Segregation = 0; Case-control = 0 Family 5 total = 0.2 PMID: 37490907 – Family 6 – one proband. Case-level (AR compound heterozygous; one predicted null + one non-LOF missense; each variant evaluated independently; no consanguinity deduction applied) = 1.6 Segregation = 0; Case-control = 0 Family 6 total = 1.6 PMID: 37490907 – Family 7 – one proband. Case-level (non-LOF start = 0.1; homozygous missense; no consanguinity deduction applied) = 0.1; Segregation = 0; Case-control = 0 Family 7 total = 0.1 Published genetic evidence total = 0.1 + 1.5 + 2.1 + 2.1 + 0.2 + 1.6 + 0.1 = 5.6 / 12 (Capped at 12) Genetic evidence – Our case Family 1 – One proband. Case-level (biallelic predicted null in AR model; homozygous nonsense; no consanguinity deduction applied) = 1.5; Segregation = 0; Case-control = 0 Family 1 total = 1.5 Total genetic evidence (published AR + our case) 5.6 (published AR) + 1.5 (our case) = 7.1 / 12 Experimental evidence – Published PMID: 37490907 – Liver immunohistochemistry and flow cytometry show absent/markedly reduced stabilin-1 in liver sinusoidal endothelial cells, monocytes, and monocyte-derived macrophages from affected individuals (supports loss-of-function mechanism). Functional alteration (patient-derived tissues/cells; conservative single line item) = 1.0 PMID: 37490907 – STAB1 encodes stabilin-1, a scavenger receptor involved in receptor-mediated endocytosis/sorting; proposed role in ferritin clearance/metabolism aligns with isolated hyperferritinemia phenotype. Gene function / biological plausibility = 0.5 Experimental evidence total = 1.5 / 6 Overall score Genetic evidence = 12 Experimental evidence = 1.5 Overall score = 8.6 / 18
Inheritance Pattern: AR
Disease ID:MONDO:0958237
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STAB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015136.3. 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 | 15 | 14 | 5 | 34 | ||
| missense | 454 | 34 | 1 | 489 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 485 | 48 | 6 | 539 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055951.2 | 69 | MANE Select | |
| Ensembl | ENSP00000312946.6 | 69 | MANE Select | |
| Ensembl | ENSP00000418426.1 | 5 | Standard | |
| Ensembl | ENSP00000569985.1 | 69 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| stab1 | Danio rerio | Structure: vascular lymphangioblast Quality: hypoplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Scavenging by Class H Receptors
- Binding and Uptake of Ligands by Scavenger Receptors
Biological Process
- receptor-mediated endocytosis
- inflammatory response
- cell adhesion
- cell-cell signaling
- negative regulation of angiogenesis
Molecular Function
- low-density lipoprotein particle receptor activity
- scavenger receptor activity
- calcium ion binding
- protein binding
- hyaluronic acid binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- endocytic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000321725
- Coding exons
- 69
- Length
- 29158
- Individuals with no LoFs
- 125376
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 370
- Defined
- 125746
- p
- 0.00147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.09 | 1478 | 1.60e+3 | 0.923 | 0.000104 | 16659 |
| Missense (PolyPhen) | 419 | 553.37 | 0.75719 | 6076 | ||
| Synonymous | -1.82 | 727 | 667 | 1.09 | 0.0000459 | 5154 |
| Loss of Function | 3.60 | 102 | 149 | 0.682 | 0.00000795 | 1565 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00094 | 0.00092 | rare |
| Latino/Admixed American | 0.0017 | 0.0015 | notable |
| Ashkenazi Jewish | 0.0013 | 0.0013 | notable |
| East Asian | 0.0014 | 0.0014 | notable |
| Finnish | 0.00086 | 0.00079 | rare |
| European (Non-Finnish) | 0.0020 | 0.0019 | notable |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a scavenger receptor for acetylated low density lipoprotein. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. When inhibited in endothelial tube formation assays, there is a marked decrease in cell-cell interactions, suggesting a role in angiogenesis. Involved in the delivery of newly synthesized CHID1/SI-CLP from the biosynthetic compartment to the endosomal/lysosomal system. {ECO:0000269|PubMed:12077138, ECO:0000269|PubMed:16357325}.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.0541
- RVIS EVS
- -4.12
- RVIS percentile EVS
- 0.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.335
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |