SALL4: A Key Regulator in Development and Disease
Comprehensive genomic and functional analysis of the SALL4 gene, a critical transcription factor in embryogenesis and stem cell biology, with implications in congenital disorders and cancer.
Gene Information Card
| Symbol | SALL4 |
|---|---|
| Full Name | Spalt-like transcription factor 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 20q13.2 |
| NCBI Gene ID | 57167 ncbi.nlm.nih.gov/gene/57167 |
| Ensembl ID | ENSG00000101115 |
| UniProt ID | Q9UJQ4 |
| OMIM ID | 607343 |
| HGNC ID | 10529 |
| Aliases | ZNF797, dJ1111N23.1, HSAL4 |
Description
SALL4 (Spalt-like transcription factor 4) encodes a zinc finger transcription factor essential for embryonic development, particularly in limb, heart, and neural tube formation. It acts as a key regulator of pluripotency in embryonic stem cells and is involved in the maintenance of self-renewal. Mutations in SALL4 cause autosomal dominant disorders such as Duane-radial ray syndrome (DRRS) and IVIC syndrome. Aberrant expression is also implicated in various cancers, including leukemia and solid tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Duane-radial ray syndrome (DRRS) | Loss-of-function mutations in SALL4 disrupt normal limb and eye development, leading to radial ray defects and Duane anomaly. | OMIM #607323; ClinVar |
| IVIC syndrome | Heterozygous mutations (e.g., frameshift or nonsense) cause a syndrome featuring radial ray defects, hearing loss, and thrombocytopenia. | OMIM #147750; ClinVar |
| Acute myeloid leukemia (AML) | Overexpression of SALL4 promotes leukemogenesis by activating HOX genes and inhibiting differentiation. | COSMIC; PubMed studies |
| Hepatocellular carcinoma | Upregulation of SALL4 correlates with poor prognosis and stemness features. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Placenta | 8.2 | Low |
| Bone marrow | 6.1 | Low |
| Kidney | 4.3 | Low |
| Liver | 3.8 | Low |
| Heart | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.3 | High expression; associated with stem cell phenotype |
| HepG2 (liver cancer) | 9.7 | Moderate expression; linked to stemness |
| MCF7 (breast cancer) | 4.2 | Low expression |
| A549 (lung cancer) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2608C>T (p.Arg870*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.2269delC (p.Leu757Trpfs*12) | Frameshift | Rare | Loss of function; premature termination |
| c.1234A>G (p.Lys412Glu) | Missense | Rare | Likely loss of function; disrupts DNA binding |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein produced |
Mutation functional classification
Loss of Function (LOF)
Most SALL4 disease-associated mutations are loss-of-function, leading to haploinsufficiency. These include nonsense, frameshift, and splice-site variants that truncate or destabilize the protein, impairing transcriptional regulation of target genes.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented in SALL4; however, overexpression in cancers suggests a potential oncogenic role through aberrant activation of stem cell programs.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by interfering with wild-type SALL4 function, though evidence is limited. Most cases are consistent with haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pluripotency and self-renewal in embryonic stem cells (Reactome: R-HSA-913531)
• Hedgehog signaling pathway (KEGG: hsa04340)
• Wnt signaling pathway (KEGG: hsa04310)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
Protein Summary
SALL4 is a 1053-amino acid nuclear protein containing multiple C2H2-type zinc finger domains. It functions as a transcriptional repressor or activator depending on context, interacting with co-repressors like NuRD and co-activators such as EP300. SALL4 is critical for maintaining pluripotency in embryonic stem cells by regulating OCT4, NANOG, and SOX2. In development, it controls limb, heart, and neural tube patterning. Dysregulation contributes to congenital syndromes and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SALL4 Knockout HEK293 Cell Line | EDJ-KQ15159 | Human | 57167 | Details Get a Quote |
| SALL4 Knockout A-549 Cell Line | EDJ-KQ47931 | Human | 57167 | Details Get a Quote |
| SALL4 Knockout HCT 116 Cell Line | EDJ-KQ47932 | Human | 57167 | Details Get a Quote |
| SALL4 Knockout HeLa Cell Line | EDJ-KQ47933 | Human | 57167 | Details Get a Quote |
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