SEPTIN12

Chr 16AD

septin 12

Also known as: SEPT12, SPGF10

NCBI Gene: 124404ENSG00000140623UniProt: Q8IYM1OMIM: 611562

This protein is a filament-forming cytoskeletal GTPase that forms filamentous structures at the sperm annulus required for sperm tail structural integrity and motility during spermatogenesis. Mutations cause spermatogenic failure with autosomal dominant inheritance. The gene is not highly constrained against loss-of-function variants, consistent with its specialized role in male fertility rather than essential cellular functions.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 1.881 OMIM phenotype
Clinical Summary— SEPTIN12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 100 VUS of 154 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.88LOEUF
pLI 0.000
Z-score -1.64
OE 1.43 (1.03–1.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.54Z-score
OE missense 1.29 (1.17–1.42)
292 obs / 226.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.43 (1.03–1.88)
0≤0.351.4
Missense OE1.29 (1.17–1.42)
0≤0.61.4
Synonymous OE1.60
0≤1.21.6
LoF obs/exp: 24 / 16.8Missense obs/exp: 292 / 226.8Syn Z: -4.65
DN
0.7035th %ile
GOF
0.7028th %ile
LOF
0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
VUS100
Likely Benign8
Benign15
28
Pathogenic
100
VUS
8
Likely Benign
15
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
0
0
0
VUS
2
87
11
0
100
Likely Benign
0
5
0
3
8
Benign
0
0
13
2
15
Total292525151

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

View in ClinVar →

Protein Context — Lollipop Plot

SEPTIN12 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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
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