APAF1

apoptotic peptidase activating factor 1, the group of WD repeat domain containing|Caspase recruitment domain containing|Apoptosome

Basic information

Region (hg38): 12:98645289-98735433

Links

ENSG00000120868 ∙ NCBI:317 ∙ OMIM:602233 ∙ HGNC:576 ∙ Uniprot:O14727 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• depressive disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APAF1 gene.

• Inborn genetic diseases (29 variants)
• not provided (10 variants)
• Neural tube defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APAF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			27	5	3	35
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	28	7	4

Variants in APAF1

This is a list of pathogenic ClinVar variants found in the APAF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-98648396-A-G		not specified	Uncertain significance (Aug 16, 2021)
12-98648458-A-AT		Neural tube defect	Uncertain significance (Jan 01, 2013)
12-98648666-T-C		Inborn genetic diseases	Uncertain significance (Feb 02, 2022)
12-98648692-G-A		not specified	Likely benign (Jan 04, 2022)
12-98648758-A-C		not specified	Uncertain significance (Jun 22, 2021)
12-98648761-C-T		not specified	Uncertain significance (Nov 14, 2023)
12-98648774-C-T		not specified	Uncertain significance (Feb 14, 2023)
12-98648780-G-A		not specified	Likely benign (Sep 06, 2022)
12-98649592-G-T		not specified	Uncertain significance (Nov 03, 2023)
12-98659150-C-T		APAF1-related disorder	Likely benign (May 08, 2019)
12-98659309-C-T		not specified	Uncertain significance (Jan 24, 2024)
12-98662491-G-C		not specified	Uncertain significance (Sep 29, 2023)
12-98662511-A-G		not specified	Uncertain significance (Jun 07, 2023)
12-98662517-T-A		not specified	Uncertain significance (Mar 29, 2022)
12-98662753-T-A		not specified	Uncertain significance (Sep 06, 2022)
12-98662763-A-G		APAF1-related disorder	Likely benign (Feb 26, 2020)
12-98665549-A-T		APAF1-related disorder	Likely benign (Feb 21, 2019)
12-98665576-A-G		not specified	Uncertain significance (Sep 20, 2023)
12-98665606-C-T		not specified	Uncertain significance (Dec 16, 2023)
12-98665674-T-C		APAF1-related disorder	Benign (Dec 31, 2019)
12-98665705-A-G		not specified	Uncertain significance (Jul 14, 2023)
12-98665717-A-G		not specified	Uncertain significance (Mar 16, 2022)
12-98665722-C-T			Likely benign (Jul 31, 2018)
12-98666243-G-A		APAF1-related disorder	Likely benign (Jun 25, 2019)
12-98666331-A-T		APAF1-related disorder	Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APAF1	protein_coding	protein_coding	ENST00000551964	26	90286

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000962	1.00	125620	0	128	125748	0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	544	646	0.841	0.0000323	8276
Missense in Polyphen		107	184.08	0.58127		2366
Synonymous	-0.402	234	226	1.03	0.0000117	2277
Loss of Function	5.14	22	67.7	0.325	0.00000322	844

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00234	0.00235
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000440	0.000440
Middle Eastern	0.0000544	0.0000544
South Asian	0.000786	0.000784
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis. {ECO:0000269|PubMed:10393175, ECO:0000269|PubMed:12804598}.
• Pathway: Legionellosis - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Apoptosis - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Apoptosis Modulation and Signaling;Alzheimers Disease;TNF alpha Signaling Pathway;Parkinsons Disease Pathway;Amyotrophic lateral sclerosis (ALS);Nanomaterial induced apoptosis;Integrated Lung Cancer Pathway;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Apoptotic Signaling Pathway;TP53 Regulates Transcription of Cell Death Genes;Apoptosis Modulation by HSP70;Oxidative Damage;Protein alkylation leading to liver fibrosis;miRNA regulation of p53 pathway in prostate cancer;apoptotic signaling in response to dna damage;DNA Damage Response;Neutrophil degranulation;Gene expression (Transcription);trefoil factors initiate mucosal healing;caspase cascade in apoptosis;role of mitochondria in apoptotic signaling;hiv-1 nef: negative effector of fas and tnf;west nile virus;stress induction of hsp regulation;regulation of cell cycle progression by plk3;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Fas;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;Formation of apoptosome;Apoptotic factor-mediated response;Intrinsic Pathway for Apoptosis;Innate Immune System;Immune System;Apoptosis;Programmed Cell Death;Activation of caspases through apoptosome-mediated cleavage;TP53 Regulates Transcription of Caspase Activators and Caspases;Transcriptional Regulation by TP53;Direct p53 effectors;TNF;Cytochrome c-mediated apoptotic response;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;p75(NTR)-mediated signaling;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.545

Intolerance Scores

• loftool: 0.456
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.2

Haploinsufficiency Scores

• pHI: 0.111
• hipred: Y
• hipred_score: 0.530
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Apaf1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; skeleton phenotype; vision/eye phenotype

Gene ontology

• Biological process: response to hypoxia;kidney development;neural tube closure;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;nervous system development;aging;response to nutrient;activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c;cardiac muscle cell apoptotic process;cell differentiation;forebrain development;regulation of apoptotic process;positive regulation of apoptotic process;neutrophil degranulation;protein homooligomerization;neuron apoptotic process;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;negative regulation of G0 to G1 transition;cellular response to transforming growth factor beta stimulus;response to G1 DNA damage checkpoint signaling;intrinsic apoptotic signaling pathway;regulation of apoptotic DNA fragmentation;positive regulation of apoptotic signaling pathway
• Cellular component: extracellular region;nucleus;cytosol;protein-containing complex;secretory granule lumen;apoptosome;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: nucleotide binding;protein binding;ATP binding;cysteine-type endopeptidase activator activity involved in apoptotic process;heat shock protein binding;identical protein binding;ADP binding