BIRC2

protein-coding

baculoviral IAP repeat containing 2, the group of Baculoviral IAP repeat containing|Caspase recruitment domain containing|Ring finger proteins

Gene summary

The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. This encoded protein inhibits apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Previous symbols:

API1

MANE transcript

NM_001166.5

Inheritance

—

ClinVar variants

U:85B:4

Top phenotype

BIRC2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr11:102,347,211-102,378,670

External References & Databases

Ensembl (ENSG00000110330)

Transcript & Mutation Effects

hg38 • Region Span ~31.5 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 BIRC2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 1

BIRC2-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001166.5. 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			81 clinvar	3 clinvar		84
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	85	4	0	89

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001166.5	RefSeq	NP_001157.1	8	MANE Select
ENST00000227758.7	Ensembl	ENSP00000227758.2	8	MANE Select
NM_001256163.1	RefSeq	NP_001243092.1	8	Standard
NM_001256166.2	RefSeq	NP_001243095.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
birc2	Danio rerio	Structure: endothelial cell Quality: apoptotic abnormal

Gene / Model

Organism

Observed Phenotype

birc2

Danio rerio

Structure: endothelial cell

Quality: apoptotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Focal adhesion - Homo sapiens (human)
Small cell lung cancer - Homo sapiens (human)
Apoptosis - multiple species - Homo sapiens (human)
Ubiquitin mediated proteolysis - Homo sapiens (human)
TNF signaling pathway - Homo sapiens (human)

Biological Process

protein polyubiquitination
response to hypoxia
placenta development
apoptotic process
cell surface receptor signaling pathway

Molecular Function

transcription coactivator activity
ubiquitin-protein transferase activity
protein binding
zinc ion binding
transferase activity

Cellular Component

XY body
nucleus
cytoplasm
cytosol
cytoplasmic side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000227758
Coding exons: 8
Length: 31460
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125741
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.177	310	319	0.972	0.0000151	4087
Missense (PolyPhen)		52	99.599	0.52209		1311
Synonymous	-1.92	138	112	1.23	0.00000555	1135
Loss of Function	3.77	6	27.2	0.220	0.00000142	355

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.00024	0.00023	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin- protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase- dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle. {ECO:0000269|PubMed:15665297, ECO:0000269|PubMed:18082613, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21653699, ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969}.;

Recessive Scores

pRec: 0.297

Intolerance Scores

LoFtool: 0.410
RVIS EVS: -0.25
RVIS percentile EVS: 36.07

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.928

Gene Damage Prediction

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