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28 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SALL4
spalt like transcription factor 4
Chromosome 20 Β· 20q13.2
NCBI Gene: 57167Ensembl: ENSG00000101115.13HGNC: HGNC:15924UniProt: Q9UJQ4
204PubMed Papers
22Diseases
0Drugs
56Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedOncogeneTranscription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleoplasmprotein bindingregulation of transcription by RNA polymerase IInucleusDuane-radial ray syndromeIVIC syndromeOkihiro syndromeneurodegenerative disease
✦AI Summary

SALL4 is a zinc finger transcription factor that functions as a member of the spalt-like family of developmental genes 1. In normal development, SALL4 plays a critical role in maintaining embryonic and hematopoietic stem cell self-renewal and pluripotency through interaction with developmental regulators like OCT4 and NANOG 2. SALL4 expression normally decreases during development and is absent in most differentiated adult tissues 3. Heterozygous SALL4 mutations cause Duane-Radial Ray syndrome and related developmental syndromes characterized by limb malformations, ocular defects, and congenital heart disease 1. Notably, thalidomide induces SALL4 degradation exclusively in humans, primates, and rabbits, mechanistically explaining thalidomide's species-specific teratogenicity and producing phenotypes that mimic SALL4 loss-of-function mutations 1. In cancer, SALL4 becomes aberrantly reactivated and acts as an oncofetal gene 4. SALL4 expression is detected in ~86% of breast cancers and various other malignancies 2. SALL4 positivity significantly increases overall mortality (HR=1.4) and disease recurrence (HR=1.52) across multiple cancer types 4. SALL4 regulates cancer cell proliferation, apoptosis, metastasis, and drug resistance through epigenetic modulation as a transcriptional activator or repressor 3. In myelodysplastic syndrome, hypomethylating agent treatment can paradoxically demethylate SALL4 promoter regions and upregulate SALL4 expression in 30-40% of patients, associated with worse outcomes 5. SALL4 overexpression predicts relapse in acute lymphoblastic leukemia with 92.3% sensitivity 6, establishing SALL4 as a promising diagnostic, prognostic biomarker, and therapeutic target.

Sources cited
1
SALL4 is a zinc finger transcription factor; heterozygous SALL4 mutations cause Duane-Radial Ray syndrome; thalidomide induces SALL4 degradation in humans/primates/rabbits with species-specific effects
PMID: 30067223
2
SALL4 maintains embryonic stem cell properties; SALL4 is expressed in ~86% of breast cancers; SALL4 regulates cell growth, proliferation, and apoptosis
PMID: 27444278
3
SALL4 reactivation increases overall mortality (HR=1.4) and disease recurrence (HR=1.52) across cancer types
PMID: 28160555
4
SALL4 controls cancer cell proliferation, apoptosis, metastasis, and drug resistance; acts as transcriptional activator or repressor in epigenetic modulation
PMID: 37337914
5
Hypomethylating agents can demethylate SALL4 promoter regions and upregulate SALL4 in 30-40% of myelodysplastic syndrome patients, associated with worse outcomes
PMID: 35613022
6
SALL4 overexpression in acute lymphoblastic leukemia predicts relapse with 92.3% sensitivity and shorter overall/disease-free survival
PMID: 34782707
Disease Associationsβ“˜22
Duane-radial ray syndromeOpen Targets
0.82Strong
IVIC syndromeOpen Targets
0.72Strong
Okihiro syndromeOpen Targets
0.68Moderate
neurodegenerative diseaseOpen Targets
0.55Moderate
appendicitisOpen Targets
0.42Moderate
hepatocellular carcinomaOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.40Weak
melanomaOpen Targets
0.39Weak
colorectal adenocarcinomaOpen Targets
0.38Weak
gastric adenocarcinomaOpen Targets
0.37Weak
Duane retraction syndromeOpen Targets
0.37Weak
colon adenocarcinomaOpen Targets
0.37Weak
gastrointestinal stromal tumorOpen Targets
0.37Weak
hearing lossOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
Okihiro syndrome due to a point mutationOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
Duane-radial ray syndromeUniProt
IVIC syndromeUniProt
Pathogenic Variants56
NM_020436.5(SALL4):c.1242_1245del (p.Cys415fs)Pathogenic
Duane-radial ray syndrome|SALL4-Related Disorders
β˜…β˜…β˜†β˜†2025β†’ Residue 415
NM_020436.5(SALL4):c.2491C>T (p.Arg831Ter)Pathogenic
not provided|Duane-radial ray syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 831
NM_020436.5(SALL4):c.1717C>T (p.Arg573Ter)Pathogenic
Duane-radial ray syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 573
NM_020436.5(SALL4):c.2593C>T (p.Arg865Ter)Pathogenic
Duane-radial ray syndrome|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 865
NM_020436.5(SALL4):c.516_522del (p.Gly174fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 174
NM_020436.5(SALL4):c.131-2delPathogenic
not provided|Oculootoradial syndrome|Duane-radial ray syndrome
β˜…β˜…β˜†β˜†2020
NM_020436.5(SALL4):c.2665G>T (p.Glu889Ter)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 889
NM_020436.5(SALL4):c.1414_1420del (p.Leu472fs)Likely pathogenic
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 472
NM_020436.5(SALL4):c.2280dup (p.Asn761fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 761
NM_020436.5(SALL4):c.496dup (p.Gln166fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 166
NM_020436.5(SALL4):c.713del (p.Gln238fs)Likely pathogenic
SALL4-Related Disorders
β˜…β˜†β˜†β˜†2024β†’ Residue 238
NM_020436.5(SALL4):c.1557del (p.Thr520fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 520
NM_020436.5(SALL4):c.1975_1988del (p.Leu658_Pro659insTer)Likely pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 658
NM_020436.5(SALL4):c.1291C>T (p.Arg431Ter)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 431
NM_020436.5(SALL4):c.2101del (p.Ala701fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 701
NM_020436.5(SALL4):c.474_475del (p.Glu158fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 158
NM_020436.5(SALL4):c.1801C>T (p.Arg601Ter)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 601
NM_020436.5(SALL4):c.2424dup (p.Ala809fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 809
NM_020436.5(SALL4):c.1994_1995del (p.Phe665fs)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 665
NM_020436.5(SALL4):c.1657C>T (p.Gln553Ter)Pathogenic
Duane-radial ray syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 553
View on ClinVar β†—
Related Genes
NANOGProtein interaction100%POU5F1Protein interaction100%SOX2Protein interaction98%RBBP4Protein interaction97%SALL1Protein interaction94%ESRRBProtein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
23%
Ovary
3%
Heart
2%
Lung
1%
Brain
1%
Gene Interaction Network
Click a node to explore
SALL4NANOGPOU5F1SOX2RBBP4SALL1ESRRB
PROTEIN STRUCTURE
Preparing viewer…
PDB7BQV Β· 1.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.18Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.09 [0.05–0.18]
RankingsWhere SALL4 stands among ~20K protein-coding genes
  • #2,063of 20,598
    Most Researched204 Β· top quartile
  • #1,224of 5,498
    Most Pathogenic Variants56 Β· top quartile
  • #362of 17,882
    Most Constrained (LOEUF)0.18 Β· top 5%
Genes detectedSALL4
Sources retrieved28 papers
Response timeβ€”
πŸ“„ Sources
28β–Ό
1
PMID: 20301547
1.00
2
SMARCA4/BRG1-Deficient Non-Small Cell Lung Carcinomas: A Case Series and Review of the Literature.
PMID: 33367658
Arch Pathol Lab Med Β· 2021
0.90
3
Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome.
PMID: 30067223
Elife Β· 2018
0.80
4
SALL4 is a CRL3
PMID: 38062245
Cell Death Differ Β· 2024
0.76
5
SALL4 and microRNA: The Role of Let-7.
PMID: 34573282
Genes (Basel) Β· 2021
0.72