BIRC6

protein-coding

baculoviral IAP repeat containing 6, the group of MicroRNA protein coding host genes|Baculoviral IAP repeat containing|Ubiquitin conjugating enzymes E2

Gene summary

This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016252.4

Inheritance

—

ClinVar variants

P:1U:605B:81

Top phenotype

BIRC6-related disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr2:32,357,023-32,619,571

External References & Databases

Ensembl (ENSG00000115760)

Transcript & Mutation Effects

hg38 • Region Span ~262.5 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 BIRC6 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 515

BIRC6-related disorderTotal: 83

not providedTotal: 58

Hereditary breast ovarian cancer syndromeTotal: 1

Autism spectrum disorderTotal: 1

Premature ovarian insufficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016252.4. 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			14 clinvar	35 clinvar	22 clinvar	71
missense	1 clinvar		557 clinvar	13 clinvar	11 clinvar	582
nonsense			9 clinvar			9
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			20 clinvar			20
Total	1	0	605	48	33	687

Highest pathogenic variant AF is 0.000033004573

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016252.4	RefSeq	NP_057336.3	74	MANE Select
ENST00000421745.7	Ensembl	ENSP00000393596.2	74	MANE Select
NM_001378125.1	RefSeq	NP_001365054.1	74	Standard
ENST00000431454.2	Ensembl	ENSP00000393590.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Apoptosis - multiple species - Homo sapiens (human)
Ubiquitin mediated proteolysis - Homo sapiens (human)
Apoptosis Modulation and Signaling

Biological Process

protein phosphorylation
ubiquitin-dependent protein catabolic process
apoptotic process
cell cycle
positive regulation of cell population proliferation

Molecular Function

ubiquitin-protein transferase activity
cysteine-type endopeptidase inhibitor activity
protein binding
ubiquitin conjugating enzyme activity

Cellular Component

spindle pole
nucleus
endosome
trans-Golgi network
microtubule organizing center

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000421745
Coding exons: 74
Length: 261871
Individuals with no LoFs: 125558
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125609
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.21	1964	2.41e+3	0.816	0.000122	31421
Missense (PolyPhen)		694	1097.4	0.6324		14419
Synonymous	-1.87	949	879	1.08	0.0000452	9686
Loss of Function	12.5	14	210	0.0666	0.0000108	2822

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00034	0.00032	rare
South Asian	0.000033	0.000033	rare
Other	0.00071	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its tragets include CASP9 and DIABLO/SMAC. Acts as an inhibitor of CASP3, CASP7 and CASP9. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification. {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:18329369}.;

Recessive Scores

pRec: 0.0958

Intolerance Scores

LoFtool: 0.389
RVIS EVS: -4.33
RVIS percentile EVS: 0.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.892

Gene Damage Prediction

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