GeneBe

SATB1

protein-coding

SATB homeobox 1, the group of CUT class homeoboxes and pseudogenes

Gene summary

This gene encodes a matrix protein which binds nuclear matrix and scaffold-associating DNAs through a unique nuclear architecture. The protein recruits chromatin-remodeling factors in order to regulate chromatin structure and gene expression. [provided by RefSeq, Apr 2016]

MANE transcript

NM_002971.6

Inheritance

AD

ClinVar variants

P:39U:165B:30

Top phenotype

Developmental delay with dysmorphic facies and dental anomalies; den Hoed-de Boer-Voisin syndrome (Kohlschutter-Tonz syndrome-like)

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr3:18,345,377-18,445,621

External References & Databases

Ensembl (ENSG00000182568)NCBI Gene (6304)OMIM (602075)HGNC:10541GenCCUniProt (Q01826)AlphaFoldClinVar (SATB1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~100.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

developmental delay with dysmorphic facies and dental anomaliesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030988

Submitter: Labcorp Genetics (formerly Invitae)

complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: ClinGen

*SATB1* was first reported in relation to autosomal dominant complex neurodevelopmental disorder in 2021 in a case study of 42 individuals (den Hoed et al., PMID: 33513338). Individuals with missense mutations in one of the DNA-binding domains (CUT1 and CUT2) were characterized by global developmental delay, moderate to severe intellectual disability, dysmorphic features, teeth abnormalities, autistic features, and early-onset epilepsy. Those with nonsense or frameshift mutations were characterized by mild global developmental delay with variably impaired intellectual development and autistic behaviors (PMIDs: 33513338, 34615535). Given the spectrum of neurodevelopmental features observed, the gene is curated for autosomal dominant complex neurodevelopmental disorder. Twenty-five variants (missense, nonsense, frameshift, and splice variant) that have been reported in 34 probands in 2 publications (PMIDs: 33513338, 34615535) are included in this curation. Both females and males were equally affected and most reported variants were de novo. Recurrence of a few missense variants was observed in non-related individuals. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. In summary, there is definitive evidence supporting the relationship between *SATB1* and autosomal dominant complex neurodevelopmental disorder. This has been repeatedly demonstrated in both research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism expert panel on September 17th 2024 (SOP Version 10).

Clinical Genomic Database (CGD)

Developmental delay with dysmorphic facies and dental anomalies; den Hoed-de Boer-Voisin syndrome (Kohlschutter-Tonz syndrome-like)AD

Manifestation: Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Cardiovascular

Rationale: The conditions can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 33513338Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SATB1 variants in ClinVar

11 Conditions Cataloged
not providedTotal: 134
Inborn genetic diseasesTotal: 59
Developmental delay with dysmorphic facies and dental anomaliesTotal: 38
SATB1-related disorderTotal: 25
not specifiedTotal: 21
Kohlschutter-Tonz syndrome-likeTotal: 20
Neurodevelopmental disorderTotal: 2
Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002971.6. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
21
clinvar
1
clinvar
 25
missense
3
clinvar
10
clinvar
144
clinvar
8
clinvar
 165
nonsense
4
clinvar
3
clinvar
4
clinvar
 11
start loss
0
frameshift
10
clinvar
8
clinvar
9
clinvar
 27
splice donor/acceptor (+/-2bp)
1
clinvar
5
clinvar
 6
Total1722165291234

Highest pathogenic variant AF is 0.000006574449

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002971.6RefSeqNP_002962.110MANE Select
ENST00000338745.11EnsemblENSP00000341024.510MANE Select
NM_001131010.4RefSeqNP_001124482.110Standard
NM_001195470.3RefSeqNP_001182399.111Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
satb1bDanio rerio

Structure: thrombocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Vitamin D Receptor Pathway
  • SUMOylation of chromatin organization proteins
  • Post-translational protein modification
  • SUMO E3 ligases SUMOylate target proteins
  • Metabolism of proteins

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • chromatin organization
  • chromatin remodeling
  • epidermis development
  • viral process

Molecular Function

  • RNA polymerase II regulatory region sequence-specific DNA binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • DNA-binding transcription repressor activity, RNA polymerase II-specific
  • chromatin binding
  • double-stranded DNA binding

Cellular Component

  • nucleus
  • nucleoplasm
  • nuclear heterochromatin
  • nuclear matrix
  • nuclear body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000417717
Coding exons
11
Length
100202
Individuals with no LoFs
125742
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
125748
p
0.0000239
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.982024360.4630.00002475204
Missense (PolyPhen)49156.490.313121864
Synonymous-1.071921741.100.00001091550
Loss of Function5.02640.40.1480.00000222431

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000380.000035rare
South Asian00.0absent
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma (By similarity). Binds to DNA at special AT-rich sequences, the consensus SATB1-binding sequence (CSBS), at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcriptional repressor controlling nuclear and viral gene expression in a phosphorylated and acetylated status-dependent manner, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes (e.g. PML at the MHC-I locus) and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Modulates genes that are essential in the maturation of the immune T-cell CD8SP from thymocytes. Required for the switching of fetal globin species, and beta- and gamma-globin genes regulation during erythroid differentiation. Plays a role in chromatin organization and nuclear architecture during apoptosis. Interacts with the unique region (UR) of cytomegalovirus (CMV). Alu-like motifs and SATB1- binding sites provide a unique chromatin context which seems preferentially targeted by the HIV-1 integration machinery. Moreover, HIV-1 Tat may overcome SATB1-mediated repression of IL2 and IL2RA (interleukin) in T-cells by binding to the same domain than HDAC1. Delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. Reprograms chromatin organization and the transcription profiles of breast tumors to promote growth and metastasis. {ECO:0000250, ECO:0000269|PubMed:10595394, ECO:0000269|PubMed:11463840, ECO:0000269|PubMed:12374985, ECO:0000269|PubMed:12692553, ECO:0000269|PubMed:1505028, ECO:0000269|PubMed:15618465, ECO:0000269|PubMed:15713622, ECO:0000269|PubMed:16377216, ECO:0000269|PubMed:16630892, ECO:0000269|PubMed:17173041, ECO:0000269|PubMed:17376900, ECO:0000269|PubMed:18337816, ECO:0000269|PubMed:19103759, ECO:0000269|PubMed:19247486, ECO:0000269|PubMed:19332023, ECO:0000269|PubMed:19430959, ECO:0000269|PubMed:9111059, ECO:0000269|PubMed:9548713}.;

Recessive Scores

pRec
0.158

Intolerance Scores

LoFtool
0.363
RVIS EVS
-0.58
RVIS percentile EVS
18.59

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.896

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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