AIFM3

protein-coding

apoptosis inducing factor mitochondria associated 3

Gene summary

Predicted to enable oxidoreductase activity, acting on NAD(P)H. Involved in execution phase of apoptosis. Located in endoplasmic reticulum and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001386814.1

Inheritance

—

ClinVar variants

U:98B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr22:20,965,108-20,981,360

External References & Databases

Ensembl (ENSG00000183773)

Transcript & Mutation Effects

hg38 • Region Span ~16.3 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 AIFM3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001386814.1. 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 clinvar		2
missense			94 clinvar	1 clinvar		95
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	98	2	0	100

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 87 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001386814.1	RefSeq	NP_001373743.1	20	MANE Select
ENST00000440238.4	Ensembl	ENSP00000390798.2	20	MANE Select
NM_001018060.3	RefSeq	NP_001018070.1	19	Standard
NM_001146288.2	RefSeq	NP_001139760.1	19	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
aifm3	Danio rerio	Structure: pronephric proximal convoluted tubule Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

aifm3

Danio rerio

Structure: pronephric proximal convoluted tubule

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

oxidation-reduction process
execution phase of apoptosis

Molecular Function

oxidoreductase activity
metal ion binding
flavin adenine dinucleotide binding
2 iron, 2 sulfur cluster binding

Cellular Component

nucleus
mitochondrion
mitochondrial inner membrane
endoplasmic reticulum
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399167
Coding exons: 20
Length: 16254
Individuals with no LoFs: 125570
Homozygous LoFs: 1
Heterozygous LoFs: 177
Defined: 125748
p: 0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.998	329	384	0.857	0.0000245	3890
Missense (PolyPhen)		130	138.82	0.93644		1398
Synonymous	0.122	161	163	0.988	0.0000112	1203
Loss of Function	1.61	27	37.7	0.716	0.00000210	390

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00065	0.00062	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00069	0.00069	rare
East Asian	0.00083	0.00082	rare
Finnish	0.0018	0.0017	notable
European (Non-Finnish)	0.00074	0.00073	rare
South Asian	0.00039	0.00039	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces apoptosis through a caspase dependent pathway. Reduces mitochondrial membrane potential. {ECO:0000269|PubMed:15764604}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

RVIS EVS: -0.19
RVIS percentile EVS: 39.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

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