NACA

protein-coding

nascent polypeptide associated complex subunit alpha

Gene summary

This gene encodes a protein that associates with basic transcription factor 3 (BTF3) to form the nascent polypeptide-associated complex (NAC). This complex binds to nascent proteins that lack a signal peptide motif as they emerge from the ribosome, blocking interaction with the signal recognition particle (SRP) and preventing mistranslocation to the endoplasmic reticulum. This protein is an IgE autoantigen in atopic dermatitis patients. Alternative splicing results in multiple transcript variants, but the full length nature of some of these variants, including those encoding very large proteins, has not been determined. There are multiple pseudogenes of this gene on different chromosomes. [provided by RefSeq, Feb 2016]

MANE transcript

NM_001365896.1

Inheritance

—

ClinVar variants

U:163B:31

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr12:56,712,305-56,731,628

External References & Databases

Ensembl (ENSG00000196531)

UniProt (E9PAV3, Q13765)

Transcript & Mutation Effects

hg38 • Region Span ~19.3 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 NACA variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 25

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365896.1. 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			7 clinvar	22 clinvar	1 clinvar	30
missense			147 clinvar	6 clinvar	2 clinvar	155
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	163	28	3	194

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 91 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365896.1	RefSeq	NP_001352825.1	8	MANE Select
ENST00000454682.6	Ensembl	ENSP00000403817.1	8	MANE Select
NM_001113201.3	RefSeq	NP_001106672.1	7	Standard
NM_001113202.2	RefSeq	NP_001106673.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
naca	Danio rerio	Structure: neutrophil Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

naca

Danio rerio

Structure: neutrophil

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrin-linked kinase signaling

Molecular Function

DNA binding

Cellular Component

nucleus
nascent polypeptide-associated complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000550952
Coding exons: 10
Length: 19201
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.896	424	479	0.885	0.0000227	5803
Missense (PolyPhen)		17	24.181	0.70303		359
Synonymous	-0.262	190	185	1.02	0.00000917	2156
Loss of Function	2.78	12	27.8	0.431	0.00000126	365

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cardiac- and muscle-specific transcription factor. May act to regulate the expression of genes involved in the development of myotubes. Plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. Involved in the organized assembly of thick and thin filaments of myofibril sarcomeres (By similarity). {ECO:0000250|UniProtKB:P70670}.;

Recessive Scores

pRec: 0.203

Intolerance Scores

LoFtool: 0.531
RVIS EVS: 1.65
RVIS percentile EVS: 96.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.874

Gene Damage Prediction

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