BIRC7

protein-coding

baculoviral IAP repeat containing 7, the group of MicroRNA protein coding host genes|Ring finger proteins|Baculoviral IAP repeat containing

Gene summary

This gene encodes a member of the inhibitor of apoptosis protein (IAP) family, and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is essential for inhibitory activity and interacts with caspases, while the RING finger domain sometimes enhances antiapoptotic activity but does not inhibit apoptosis alone. Elevated levels of the encoded protein may be associated with cancer progression and play a role in chemotherapy sensitivity. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jul 2013]

MANE transcript

NM_139317.3

Inheritance

—

ClinVar variants

U:39B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr20:63,235,883-63,240,495

External References & Databases

Ensembl (ENSG00000101197)

Transcript & Mutation Effects

hg38 • Region Span ~4.6 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 BIRC7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139317.3. 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						0
missense			39 clinvar	8 clinvar	2 clinvar	49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	8	2	49

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139317.3	RefSeq	NP_647478.1	6	MANE Select
ENST00000217169.8	Ensembl	ENSP00000217169.3	6	MANE Select
NM_022161.4	RefSeq	NP_071444.1	6	Standard
ENST00000342412.10	Ensembl	ENSP00000345213.6	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Small cell lung cancer - Homo sapiens (human)
Apoptosis - multiple species - Homo sapiens (human)
Ubiquitin mediated proteolysis - Homo sapiens (human)
Toxoplasmosis - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)

Biological Process

apoptotic process
activation of JUN kinase activity
protein ubiquitination
regulation of cell population proliferation
negative regulation of apoptotic process

Molecular Function

ubiquitin-protein transferase activity
cysteine-type endopeptidase inhibitor activity
protein binding
enzyme binding
cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Cellular Component

nucleus
cytoplasm
Golgi apparatus
microtubule organizing center
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217169
Coding exons: 6
Length: 4625
Individuals with no LoFs: 125490
Homozygous LoFs: 0
Heterozygous LoFs: 95
Defined: 125585
p: 0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00982	191	191	1.00	0.0000126	1889
Missense (PolyPhen)		45	46.779	0.96196		487
Synonymous	-1.01	95	83.3	1.14	0.00000578	615
Loss of Function	0.603	12	14.5	0.829	6.20e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0033	0.0033	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00046	0.00046	rare
Other	0.00051	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions. Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and NR2C2/TAK1. In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9. Isoform 1 blocks staurosporine-induced apoptosis. Isoform 2 blocks etoposide-induced apoptosis. Isoform 2 protects against natural killer (NK) cell killing whereas isoform 1 augments killing. {ECO:0000269|PubMed:11084335, ECO:0000269|PubMed:16729033, ECO:0000269|PubMed:17294084, ECO:0000269|PubMed:18034418}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.521
RVIS EVS: 0.64
RVIS percentile EVS: 84.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.650

Gene Damage Prediction

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