SP4

Chr 7

Sp4 transcription factor

NCBI Gene: 6671ENSG00000105866UniProt: Q02446

Binds to GT and GC boxes promoters elements. Probable transcriptional activator

0
ClinVar variants
0
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— SP4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.993
Z-score 4.62
OE 0.12 (0.06–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.94 (0.87–1.03)
386 obs / 408.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.06–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.87–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 4 / 32.4Missense obs/exp: 386 / 408.5Syn Z: -0.74

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SP4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mapping genomic loci implicates genes and synaptic biology in schizophrenia.
Trubetskoy V et al.·Nature
2022
Specificity Proteins (Sp) and Cancer.
Safe S·Int J Mol Sci
2023Review
Anti-Sp4 and anti-CCAR1 autoantibodies in UK vs US patients with adult and juvenile-onset anti-TIF1γ-positive myositis.
McMorrow FK et al.·Rheumatology (Oxford)
2025Cohort
Metformin-induced anticancer activities: recent insights.
Safe S et al.·Biol Chem
2018Review
Transcription factor Sp1, also known as specificity protein 1 as a therapeutic target.
Safe S et al.·Expert Opin Ther Targets
2014Review
Sp1 transcription factor: A long-standing target in cancer chemotherapy.
Vizcaíno C et al.·Pharmacol Ther
2015Review
Natural Products as Mechanism-based Anticancer Agents: Sp Transcription Factors as Targets.
Safe S et al.·Phytother Res
2016Review
Association of the Asn306Ser variant of the SP4 transcription factor and an intronic variant in the beta-subunit of transducin with digenic disease.
Gao YQ et al.·Mol Vis
2007
Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.
Sherman MA et al.·Arthritis Rheumatol
2023
Altered volume of thalamic nuclei and genetic expression in first-episode psychotic patients, and their association with childhood adversity.
Elvira UKA et al.·Prog Neuropsychopharmacol Biol Psychiatry
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Periodontal Disease (PD)Cardio Vascular DiseaseOral-Systemic Link

PMPR and Chlorhexidine on Periodontal Disease and Vascular Function

NOT YET RECRUITING
NCT07311512Phase NAMahdi MutaharStarted 2026-01-23
Chlorhexidine (0.2%) mouthwashPlacebo mouthwash

External Resources

Links to major genomics databases and tools