SEPTIN12

Chr 16AD

septin 12

Also known as: SEPT12, SPGF10

NCBI Gene: 124404ENSG00000140623UniProt: Q8IYM1

This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Primary Disease Associations & Inheritance

Spermatogenic failure 10MIM #614822
AD
151
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEPTIN12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 100 VUS of 151 total submissions

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

Tolerant to missense variation

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.1.43 (1.03–1.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.29 (1.17–1.42)
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.1.60
0≤1.21.6
LoF obs/exp: 24 / 16.8Missense obs/exp: 292 / 226.8Syn Z: -4.65

ClinVar Variant Classifications

151 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
1
87
12
0
100
Likely Benign
0
5
0
3
8
Benign
0
0
13
2
15
Total192535151

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SEPTIN 12; SEPTIN12
MIM #611562 · *

Spermatogenic failure 10

MIM #614822

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SUN5 interacts with nuclear membrane LaminB1 and cytoskeletal GTPase Septin12 mediating the sperm head-and-tail junction.
Zhang Y et al.·Mol Hum Reprod
2024
Regulation of septin phosphorylation: SEPT12 phosphorylation in sperm septin assembly.
Lin CH et al.·Cytoskeleton (Hoboken)
2019Review
SEPTIN12 genetic variants confer susceptibility to teratozoospermia.
Lin YH et al.·PLoS One
2012
SEPTIN12 c.474 G > A polymorphism as a risk factor in teratozoospermic patients.
Özkara G et al.·Mol Biol Rep
2021Cohort
SEPT12-NDC1 Complexes Are Required for Mammalian Spermiogenesis.
Lai TH et al.·Int J Mol Sci
2016
Single nucleotide polymorphisms in the SEPTIN12 gene may be associated with azoospermia by meiotic arrest in Japanese men.
Miyamoto T et al.·J Assist Reprod Genet
2012
Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects.
Li Y et al.·Hum Reprod
2021Cohort
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools