SP6

Chr 17AD

Sp6 transcription factor

Also known as: AI1K, EPFN, EPIPROFIN, KLF14

NCBI Gene: 80320UniProt: Q3SY56

SP6 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IKMIM #620104
AD
5
Active trials
66
ClinVar variants
10
Pathogenic / LP
1.3
Missense Z
0.76
LOEUF
11
Pubs (2 yr)
Clinical Summary— SP6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 55 VUS of 66 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — SP6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.76LOEUF
pLI 0.150
Z-score 2.09
OE 0.29 (0.13–0.76)
Tolerant

Typical tolerance to LoF variation

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.
1.34Z-score
OE missense 0.75 (0.66–0.85)
169 obs / 225.8 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.0.29 (0.13–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.66–0.85)
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.0.90
0≤1.21.6
LoF obs/exp: 3 / 10.2Missense obs/exp: 169 / 225.8Syn Z: 0.83

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS55
Benign1
9
Pathogenic
1
Likely Pathogenic
55
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
7
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
52
3
0
55
Likely Benign
0
0
0
0
0
Benign
0
1
0
0
1
Total05511066

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SP6 · 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

Amelogenesis imperfecta, type IK

MIM #620104

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
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
Electro-acupuncture for central obesity: a patient-assessor blinded, randomized sham-controlled clinical trial.
Lam TF et al.·BMC Complement Med Ther
2024
The efficacy and cerebral mechanism of intradermal acupuncture for major depressive disorder: a multicenter randomized controlled trial.
Wu X et al.·Neuropsychopharmacology
2025Functional
Improvement of endocrine and metabolic conditions in patients with polycystic ovary syndrome through acupuncture and its combined therapies: a systematic review and meta-analysis.
Wu T et al.·Ann Med
2025Meta-analysis
Acupuncture as an adjunctive therapy for gastric ulcer: A modified Delphi consensus study.
Sun LQ et al.·Complement Ther Med
2023
Acupuncture for senile insomnia: A systematic review of acupuncture point.
Lu G et al.·Arch Gerontol Geriatr
2024Review
Epiprofin/Sp6: a new player in the regulation of tooth development.
Jimenez-Rojo L et al.·Histol Histopathol
2010Review
Acupressure and Dementia: A Review of Current Evidence.
Liang Ooi S et al.·Altern Ther Health Med
2023Review
Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial.
Wang HX et al.·J Integr Med
2025
Acupuncture treatment of urticaria.
Chen CJ et al.·Arch Dermatol
1998
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
A Study on the Regularity of Acupoint Match Based on Association Rules with SP6 as the Main Acupoint and Its Clinical Application
Cheng W et al.·Int J Gen Med
2023
Combination of Acupoints for Alzheimer's Disease: An Association Rule Analysis
Wang YC et al.·Front Neurosci
2022
Utilizing Silk Sericin as a Biomaterial for Drug Encapsulation in a Hydrogel Matrix with Polycaprolactone: Formulation and Evaluation of Antibacterial Activity
Deb D et al.·ACS Omega
2024
Altered fractional amplitude of low-frequency fluctuation in women with premenstrual syndrome via acupuncture at Sanyinjiao (SP6)
Duan G et al.·Ann Gen Psychiatry
2021
Photochemical OFF/ON Cytotoxicity Switching by Using a Photochromic Surfactant with Visible Light Irradiation
Shinohara M et al.·ACS Omega
2022
Acupuncture versus Lornoxicam in the Treatment of Acute Renal Colic: A Randomized Controlled Trial
Zhang X et al.·J Pain Res
2021
pH modulates the role of SP6 RNA polymerase in transcription process: an in silico study.
Singh SR et al.·J Biomol Struct Dyn
2023
Top 7 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Elderly Patients (&gt;65 Years)Non-Small Cell Lung CancerPD-1 Inhibitors

Electroacupuncture Combined With PD-1 Inhibitor for Elderly Patients With Advanced NSCLC

RECRUITING
NCT07086300Phase NAKong FanmingStarted 2025-07-08
Electroacupuncture (EA)Sham electroacupuncture
Acupuncture TreatmentHormone Receptor-Positive Breast CancerHot Flashes

A Randomized Controlled Trial of Acupuncture for the Management of Hot Flashes in Patients With Hormone Receptor-Positive Breast Cancer

NOT YET RECRUITING
NCT07294339Phase NAPeking University People's HospitalStarted 2025-12-10
True AcupunctureSham Acupuncture
Hot FlashesMenopause Surgical

Acupuncture With/Without Self-acupressure for Post-oophorectomy Hot Flashes in BRCA Carriers

NOT YET RECRUITING
NCT05331209Phase NAShaare Zedek Medical CenterStarted 2026-01-01
AcupunctureAcupuncture-Acupressure
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)Erectile DysfunctionsAcupuncture

Acupuncture for Erectile Dysfunction

NOT YET RECRUITING
NCT07324148Phase NAGuang'anmen Hospital of China Academy of Chinese Medical SciencesStarted 2026-01-01
AcupunctureSham acupuncture
Non-Small Cell Lung CancerElectroacupuncturePD-1 Inhibitors

Electroacupuncture Combined With PD-1 Inhibitor for ECOG2 Advanced NSCLC

RECRUITING
NCT07239661Phase NAKong FanmingStarted 2025-11-30
Electroacupuncture (EA)Sham electroacupuncture

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