GeneBe

SP1

protein-coding

Sp1 transcription factor, the group of Zinc fingers C2H2-type|Sp transcription factors

Gene summary

The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

MANE transcript

NM_138473.3

Inheritance

—

ClinVar variants

U:75B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr12:53,380,176-53,416,446

External References & Databases

Ensembl (ENSG00000185591)NCBI Gene (6667)OMIM (189906)HGNC:11205GenCCUniProt (P08047)AlphaFoldClinVar (SP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~36.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SP1 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 70
not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138473.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
3
clinvar
 7
missense
71
clinvar
 71
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00753381
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_138473.3RefSeqNP_612482.26MANE Select
ENST00000327443.9EnsemblENSP00000329357.46MANE Select
NM_001251825.2RefSeqNP_001238754.16Standard
NM_003109.1RefSeqNP_003100.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cortisol synthesis and secretion - Homo sapiens (human)
  • TGF-beta signaling pathway - Homo sapiens (human)
  • Choline metabolism in cancer - Homo sapiens (human)
  • Cushing,s syndrome - Homo sapiens (human)
  • Breast cancer - Homo sapiens (human)

Biological Process

  • regulation of transcription, DNA-templated
  • regulation of transcription by RNA polymerase II
  • positive regulation of gene expression
  • viral process
  • cellular response to insulin stimulus

Molecular Function

  • RNA polymerase II regulatory region sequence-specific DNA binding
  • RNA polymerase II proximal promoter sequence-specific DNA binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • proximal promoter sequence-specific DNA binding
  • RNA polymerase II repressing transcription factor binding

Cellular Component

  • nuclear chromatin
  • nucleus
  • nucleoplasm
  • cytoplasm
  • transcriptional repressor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000327443
Coding exons
6
Length
36271
Individuals with no LoFs
125725
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
125726
p
0.00000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.143594250.8450.00002175106
Missense (PolyPhen)4856.1160.85538578
Synonymous-1.531861611.150.000008061665
Loss of Function5.06029.90.000.00000144310

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000880.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR- alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component ARNTL/BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21798247}.;

Recessive Scores

pRec
0.767

Intolerance Scores

RVIS EVS
-0.93
RVIS percentile EVS
9.55

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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