SP9

Chr 2

Sp9 transcription factor

Also known as: ZNF990

NCBI Gene: 100131390ENSG00000217236UniProt: P0CG40OMIM: 621003

This transcription factor regulates FGF8 expression during limb development and is essential for proper limb outgrowth during embryogenesis. Mutations cause autosomal dominant limb defects and developmental abnormalities affecting the extremities. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.34), indicating intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.34
Clinical Summary— SP9
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.940
Z-score 2.77
OE 0.00 (0.00–0.34)
Highly constrained

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

Missense Constraint
2.26Z-score
OE missense 0.55 (0.47–0.64)
107 obs / 196.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.34)
0≤0.351.4
Missense OE0.55 (0.47–0.64)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 0 / 8.9Missense obs/exp: 107 / 196.3Syn Z: 0.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateSP9-related neurodevelopmental disorder with or without epileptic encephalopathyOTHERAD
DN
0.4685th %ile
GOF
0.2398th %ile
LOF
0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SP9 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
The Effect of Acupuncture and Physiotherapy on Patients with Knee Osteoarthritis: A Randomized Controlled Study.
Atalay SG et al.·Pain Physician
2021Cohort
De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity.
Tessarech M et al.·Genet Med
2024
A strategic study of acupuncture for diabetic kidney disease based on meta-analysis and data mining.
Yu Y et al.·Front Endocrinol (Lausanne)
2024Meta-analysis
Efficacy of acupuncture and moxibustion therapy for simple obesity in adults: A meta-analysis of randomized controlled trials.
Yin Y et al.·Medicine (Baltimore)
2022Meta-analysis
The in vitro replication phenotype of hepatitis B virus (HBV) splice variants Sp3 and Sp9 and their impact on wild-type HBV replication.
McCoullough LC et al.·J Virol
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients