FIS1

Chr 7

fission, mitochondrial 1

Also known as: CGI-135, TTC11

NCBI Gene: 51024ENSG00000214253UniProt: Q9Y3D6

Enables identical protein binding activity; lipid binding activity; and molecular adaptor activity. Involved in several processes, including negative regulation of ATP metabolic process; negative regulation of fatty acid transport; and organelle fission. Acts upstream of or within mitochondrion organization. Located in mitochondrial outer membrane and peroxisomal membrane. Part of protein-containing complex. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2025]

53
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— FIS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 32 VUS of 53 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.55LOEUF
pLI 0.000
Z-score 0.36
OE 0.87 (0.51–1.55)
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.
0.38Z-score
OE missense 0.89 (0.75–1.07)
84 obs / 94.3 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.0.87 (0.51–1.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.75–1.07)
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.1.05
0≤1.21.6
LoF obs/exp: 8 / 9.2Missense obs/exp: 84 / 94.3Syn Z: -0.23

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS32
Likely Benign1
Benign1
17
Pathogenic
2
Likely Pathogenic
32
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
2
0
2
VUS
0
25
7
0
32
Likely Benign
0
0
0
1
1
Benign
0
0
1
0
1
Total02527153

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

View in ClinVar →

Protein Context — Lollipop Plot

FIS1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omic insight into the molecular networks of mitochondrial dysfunction in the pathogenesis of inflammatory bowel disease.
Chen J et al.·EBioMedicine
2024
Mitochondrial elongation impairs breast cancer metastasis.
Minarrieta L et al.·Sci Adv
2024
Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension.
Zhou X et al.·Circ Res
2023
Pro-Inflammatory CXCR3 Impairs Mitochondrial Function in Experimental Non-Alcoholic Steatohepatitis.
Du J et al.·Theranostics
2017
Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.
Li X et al.·J Exp Clin Cancer Res
2024Functional
Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials.
Marzetti E et al.·Int J Biochem Cell Biol
2013Review
TBC1D15/RAB7-regulated mitochondria-lysosome interaction confers cardioprotection against acute myocardial infarction-induced cardiac injury.
Yu W et al.·Theranostics
2020
METTL3 boosts mitochondrial fission and induces cardiac fibrosis after ischemia/reperfusion injury.
Ma L et al.·Int J Biol Sci
2024
Cholesterol induction in CD8(+) T cell exhaustion in colorectal cancer via the regulation of endoplasmic reticulum-mitochondria contact sites.
Shuwen H et al.·Cancer Immunol Immunother
2023
Mitochondrial health index correlates with plasma circulating cell-free mitochondrial DNA in bipolar disorder.
Cordeiro RC et al.·Mol Psychiatry
2023
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
Aortic Aneurysm and Dissection

MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta

ACTIVE NOT RECRUITING
NCT05434481Phase NAUniversity Hospital, AngersStarted 2022-09-07
Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

External Resources

Links to major genomics databases and tools