FIS1

protein-coding

fission, mitochondrial 1, the group of Tetratricopeptide repeat domain containing

Gene summary

Enables identical protein binding activity; lipid binding activity; and molecular adaptor activity. Involved in several processes, including negative regulation of ATP metabolic process; obsolete protein targeting to mitochondrion; 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, Jun 2026]

Previous symbols:

TTC11

MANE transcript

NM_016068.3

Inheritance

—

ClinVar variants

U:30B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr7:101,239,458-101,252,316

External References & Databases

Ensembl (ENSG00000214253)

Transcript & Mutation Effects

hg38 • Region Span ~12.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FIS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016068.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			27 clinvar			27
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	30	1	0	31

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016068.3	RefSeq	NP_057152.2	5	MANE Select
ENST00000223136.5	Ensembl	ENSP00000223136.4	5	MANE Select
ENST00000435848.1	Ensembl	ENSP00000413500.1	4	Standard
ENST00000442303.1	Ensembl	ENSP00000395964.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fis1	Danio rerio	Structure: chondrocyte Quality: apoptotic abnormal

Gene / Model

Organism

Observed Phenotype

fis1

Danio rerio

Structure: chondrocyte

Quality: apoptotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitophagy - animal - Homo sapiens (human)

Biological Process

mitochondrial fission
autophagy of mitochondrion
release of cytochrome c from mitochondria
protein targeting to mitochondrion
apoptotic process

Molecular Function

signaling receptor binding
protein binding
protein-containing complex binding

Cellular Component

mitochondrion
mitochondrial outer membrane
peroxisome
integral component of peroxisomal membrane
endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000223136
Coding exons: 5
Length: 12859
Individuals with no LoFs: 124789
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 124803
p: 0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.376	84	94.3	0.891	0.00000600	961
Missense (PolyPhen)		31	29.24	1.0602		321
Synonymous	-0.234	45	43.0	1.05	0.00000290	305
Loss of Function	0.364	8	9.19	0.870	3.91e-7	108

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the fragmentation of the mitochondrial network and its perinuclear clustering. Plays a minor role in the recruitment and association of the fission mediator dynamin- related protein 1 (DNM1L) to the mitochondrial surface and mitochondrial fission. Can induce cytochrome c release from the mitochondrion to the cytosol, ultimately leading to apoptosis. Also mediates peroxisomal fission. {ECO:0000269|PubMed:12783892, ECO:0000269|PubMed:12861026, ECO:0000269|PubMed:14996942, ECO:0000269|PubMed:16107562, ECO:0000269|PubMed:16118244, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.394
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium