SEPTIN9

Chr 17AD

septin 9

Also known as: AF17q25, MSF, MSF1, NAPB, PNUTL4, SEPT9, SINT1, SeptD1

NCBI Gene: 10801ENSG00000184640UniProt: Q9UHD8

This gene is a member of the septin family involved in cytokinesis and cell cycle control. This gene is a candidate for the ovarian tumor suppressor gene. Mutations in this gene cause hereditary neuralgic amyotrophy, also known as neuritis with brachial predilection. A chromosomal translocation involving this gene on chromosome 17 and the MLL gene on chromosome 11 results in acute myelomonocytic leukemia. Multiple alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Amyotrophy, hereditary neuralgicMIM #162100
AD
3
Active trials
3
Pathogenic / LP
477
ClinVar variants
6
Pubs (1 yr)
1.6
Missense Z
0.25
LOEUF· LoF intolerant
Clinical Summary— SEPTIN9
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Gene-Disease Validity (ClinGen)
neuralgic amyotrophy · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 265 VUS of 477 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — SEPTIN9
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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.
0.25LOEUF
pLI 0.996
Z-score 4.26
OE 0.08 (0.03–0.25)
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.
1.62Z-score
OE missense 0.77 (0.70–0.85)
302 obs / 392.2 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.0.08 (0.03–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.70–0.85)
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.1.18
0≤1.21.6
LoF obs/exp: 2 / 25.0Missense obs/exp: 302 / 392.2Syn Z: -1.85

ClinVar Variant Classifications

477 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS265
Likely Benign176
Benign19
Conflicting14
2
Pathogenic
1
Likely Pathogenic
265
VUS
176
Likely Benign
19
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
1
0
1
VUS
4
209
48
4
265
Likely Benign
0
3
84
89
176
Benign
0
1
11
7
19
Conflicting
—14
Total4213146100477

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

View in ClinVar →

Protein Context — Lollipop Plot

SEPTIN9 · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
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
Septin9 DNA methylation as a promising biomarker for cervical cancer.
Bu Q et al.·J Obstet Gynaecol
2023
CRISPR/Cas12a-mediated DNAzyme/split-aptamer cascade for label-free detection of site-specific DNA methylation.
Tian W et al.·Biosens Bioelectron
2025
Diagnostic efficacy and subgroup heterogeneity of SHOX2, RASSF1A, Septin9, and HOXA9 methylation in pleural effusion lymphoma.
Bo J et al.·Clin Epigenetics
2025
A systematic review and meta-analysis: the diagnostic accuracy of methylated SEPTIN9 for the detection of hepatocellular carcinoma and the clinical evaluation of its use in combination with other surveillance modalities.
Chandrapalan S et al.·Scand J Gastroenterol
2022Meta-analysis
Systematic review: non-endoscopic surveillance for colorectal neoplasia in individuals with Lynch syndrome.
van Liere ELSA et al.·Aliment Pharmacol Ther
2022Review
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