API5

protein-coding

apoptosis inhibitor 5, the group of Armadillo like helical domain containing

Gene summary

This gene encodes an apoptosis inhibitory protein whose expression prevents apoptosis after growth factor deprivation. This protein suppresses the transcription factor E2F1-induced apoptosis and also interacts with, and negatively regulates Acinus, a nuclear factor involved in apoptotic DNA fragmentation. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001142930.2

Inheritance

—

ClinVar variants

U:36B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr11:43,311,963-43,344,529

External References & Databases

Ensembl (ENSG00000166181)

Transcript & Mutation Effects

hg38 • Region Span ~32.6 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 API5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142930.2. 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			30 clinvar	1 clinvar		31
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	36	2	0	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001142930.2	RefSeq	NP_001136402.1	14	MANE Select
ENST00000531273.6	Ensembl	ENSP00000431391.1	14	MANE Select
NM_001142931.2	RefSeq	NP_001136403.1	13	Standard
NM_001243747.2	RefSeq	NP_001230676.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

apoptotic process
negative regulation of apoptotic process
negative regulation of fibroblast apoptotic process

Molecular Function

RNA binding
protein binding
fibroblast growth factor binding

Cellular Component

nucleus
spliceosomal complex
cytoplasm
membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000531273
Coding exons: 14
Length: 32567
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125657
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.92	139	276	0.504	0.0000139	3417
Missense (PolyPhen)		26	85.593	0.30376		1196
Synonymous	0.835	90	101	0.894	0.00000493	998
Loss of Function	5.16	1	33.0	0.0303	0.00000188	383

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. {ECO:0000269|PubMed:10780674, ECO:0000269|PubMed:17112319, ECO:0000269|PubMed:19387494}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.385
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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