NAIP

protein-coding

NLR family apoptosis inhibitory protein, the group of NLR family|Baculoviral IAP repeat containing

Gene summary

This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This copy of the gene is full length; additional copies with truncations and internal deletions are also present in this region of chromosome 5q13. It is thought that this gene is a modifier of spinal muscular atrophy caused by mutations in a neighboring gene, SMN1. The protein encoded by this gene contains regions of homology to two baculovirus inhibitor of apoptosis proteins, and it is able to suppress apoptosis induced by various signals. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

Previous symbols:

BIRC1

MANE transcript

NM_004536.3

Inheritance

—

ClinVar variants

U:28B:4

Top phenotype

Large for gestational age

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr5:70,968,166-71,025,339

External References & Databases

Ensembl (ENSG00000249437)

Transcript & Mutation Effects

hg38 • Region Span ~57.2 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 NAIP variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 3

Large for gestational ageTotal: 1

Gestational diabetes mellitus uncontrolledTotal: 1

Normal pregnancyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004536.3. 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			1 clinvar	2 clinvar		3
missense			25 clinvar	2 clinvar		27
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	28	4	0	32

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004536.3	RefSeq	NP_004527.2	14	MANE Select
ENST00000517649.6	Ensembl	ENSP00000428657.2	14	MANE Select
NM_001346870.2	RefSeq	NP_001333799.1	14	Standard
NM_022892.2	RefSeq	NP_075043.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Legionellosis - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
Nucleotide-binding Oligomerization Domain (NOD) pathway
Apoptosis Modulation and Signaling

Biological Process

apoptotic process
inflammatory response
nervous system development
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Molecular Function

protein binding
ATP binding
cysteine-type endopeptidase inhibitor activity involved in apoptotic process
metal ion binding

Cellular Component

cytoplasm
basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000517649
Coding exons: 14
Length: 56632
Individuals with no LoFs: 125578
Homozygous LoFs: 1
Heterozygous LoFs: 43
Defined: 125622
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.410	107	120	0.895	0.00000596	9268
Missense (PolyPhen)		32	41.048	0.77957		2502
Synonymous	0.321	43	45.8	0.940	0.00000259	2636
Loss of Function	0.890	7	10.0	0.697	5.09e-7	720

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00024	0.00023	rare
South Asian	0.00013	0.00013	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor- neuron apoptosis induced by a variety of signals. Possible role in the prevention of spinal muscular atrophy that seems to be caused by inappropriate persistence of motor-neuron apoptosis: mutated or deleted forms of NAIP have been found in individuals with severe spinal muscular atrophy.;

Recessive Scores

pRec: 0.109

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.316

Gene Damage Prediction

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