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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SMARCA1
SNF2 related chromatin remodeling ATPase 1
Chromosome X Β· Xq25-q26.1
NCBI Gene: 6594Ensembl: ENSG00000102038.16HGNC: HGNC:11097UniProt: A0A0A0MRP6
115PubMed Papers
20Diseases
0Drugs
14Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ATP-dependent activity, acting on DNAATP-dependent chromatin remodeler activityprotein bindingATP-dependent DNA/DNA annealing activityNeurodevelopmental disordernon-syndromic X-linked intellectual disabilityAbnormal brain morphologyX-linked intellectual disability
✦AI Summary

SMARCA1 is an X-linked member of the SNF2-like family of chrX remodeling proteins that functions as a negative regulator of chrX remodeling activity 1. Unlike canonical ATP-dependent chrX remodelers, SMARCA1 is catalytically inactive on DNA and nucleosomal substrates, instead generating inactive chrX remodeling complexes 12. SMARCA1 comprises the NURF complex alongside BPTF and SMARCA5 isoforms, where its composition critically influences forebrain development 3. In colorectal cancer, SMARCA1 suppresses metastatic progression through a dual mechanism: it attenuates transcription of neuropeptide FF (NPFF) by impairing ETS-family transcription factor SPIB DNA-binding capacity at the NPFF promoter, thereby blocking epithelial-mesenchymal transition and M2-macrophage polarization 4. Alternative splicing dysregulation can functionally inactivate SMARCA1, promoting cancer invasion 5. Clinically, hemizygous and de novo SMARCA1 variants cause X-linked neurodevelopmental disorder with variable severity, characterized by intellectual disability, macrocephaly, speech delay, autism spectrum features, and facial dysmorphisms 36. Loss-of-function variants in SMARCA1 have also been identified in rare neurogenetic disorders affecting brain development 7.

Sources cited
1
SMARCA1 is catalytically inactive and acts as negative regulator of chromatin remodelers
PMID: 15310751
2
SMARCA1 lacks chromatin-remodeling activity on DNA and nucleosomal substrates
PMID: 28801535
3
SMARCA1 pathogenic variants cause X-linked neurodevelopmental disorder; NURF complex composition critical for forebrain development
PMID: 41213919
4
SMARCA1 suppresses colorectal cancer metastasis by inhibiting NPFF transcription and blocking EMT and macrophage polarization
PMID: 40684839
5
Alternative splicing of SMARCA1 produces catalytically inactive SMARCA1-L isoform promoting cancer invasion
PMID: 37725664
6
Hemizygous SMARCA1 variants cause X-linked intellectual disability with macrocephaly and variable neurological symptoms
PMID: 40316778
7
Homozygous loss-of-function SMARCA1 variants identified in families with neurogenetic disorders affecting brain development
PMID: 26539891
Disease Associationsβ“˜20
Neurodevelopmental disorderOpen Targets
0.42Moderate
non-syndromic X-linked intellectual disabilityOpen Targets
0.33Weak
Abnormal brain morphologyOpen Targets
0.27Weak
X-linked intellectual disabilityOpen Targets
0.22Weak
cancerOpen Targets
0.21Weak
neoplasmOpen Targets
0.18Weak
genetic disorderOpen Targets
0.12Weak
melanomaOpen Targets
0.07Suggestive
sarcomaOpen Targets
0.07Suggestive
Patent ductus arteriosusOpen Targets
0.07Suggestive
Mobius syndromeOpen Targets
0.05Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.04Suggestive
lung adenocarcinomaOpen Targets
0.04Suggestive
urinary bladder carcinomaOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
HIV infectionOpen Targets
0.03Suggestive
acute myeloid leukemiaOpen Targets
0.03Suggestive
acute lymphoblastic leukemiaOpen Targets
0.03Suggestive
Pathogenic Variants14
NM_001282874.2(SMARCA1):c.3005G>A (p.Trp1002Ter)Pathogenic
not specified
β˜…β˜†β˜†β˜†2025β†’ Residue 1002
NM_001282874.2(SMARCA1):c.2251C>T (p.Arg751Ter)Pathogenic
not specified
β˜…β˜†β˜†β˜†2025β†’ Residue 751
NM_001282874.2(SMARCA1):c.1070T>G (p.Leu357Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 357
NM_001282874.2(SMARCA1):c.1071dup (p.Leu358fs)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 358
NM_001282874.2(SMARCA1):c.1971dup (p.Asn658Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 658
NM_001282874.2(SMARCA1):c.543dup (p.Pro182fs)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 182
NM_001282874.2(SMARCA1):c.271C>T (p.Arg91Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 91
NM_001282874.2(SMARCA1):c.565C>T (p.Arg189Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 189
NM_001282874.2(SMARCA1):c.685C>T (p.Arg229Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 229
NM_001282874.2(SMARCA1):c.757C>T (p.Arg253Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 253
NM_001282874.2(SMARCA1):c.2122C>T (p.Gln708Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 708
NM_001282874.2(SMARCA1):c.193C>T (p.Gln65Ter)Likely pathogenic
Non-syndromic X-linked intellectual disability
β˜…β˜†β˜†β˜†2024β†’ Residue 65
NM_001282874.2(SMARCA1):c.413T>G (p.Leu138Ter)Likely pathogenic
Non-syndromic X-linked intellectual disability
β˜…β˜†β˜†β˜†2024β†’ Residue 138
NM_001282874.2(SMARCA1):c.7C>T (p.Gln3Ter)Likely pathogenic
Abnormal brain morphology
β˜…β˜†β˜†β˜†β†’ Residue 3
View on ClinVar β†—
Related Genes
POLE3Protein interaction100%H2AC20Protein interaction100%H3-4Protein interaction100%H3-3BProtein interaction100%H3C13Protein interaction100%H3C12Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Liver
72%
Heart
71%
Brain
55%
Lung
19%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
SMARCA1POLE3H2AC20H3-4H3-3BH3C13H3C12
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P28370
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.27Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.18 [0.12–0.27]
RankingsWhere SMARCA1 stands among ~20K protein-coding genes
  • #4,135of 20,598
    Most Researched115 Β· top quartile
  • #2,506of 5,498
    Most Pathogenic Variants14
  • #929of 17,882
    Most Constrained (LOEUF)0.27 Β· top 10%
Genes detectedSMARCA1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.
PMID: 26539891
Neuron Β· 2015
1.00
2
The lncRNA MIR99AHG directs alternative splicing of
PMID: 37725664
Sci Signal Β· 2023
0.90
3
Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition.
PMID: 41213919
Nat Commun Β· 2025
0.80
4
SMARCA1-NPFF axis inhibits colorectal cancer metastasis by blocking epithelial-mesenchymal transition and macrophage-dependent immune reprogramming.
PMID: 40684839
Cancer Lett Β· 2025
0.70
5
CRISPR-assisted detection of RNA-protein interactions in living cells.
PMID: 32572232
Nat Methods Β· 2020
0.60