NACA2

protein-coding

nascent polypeptide associated complex subunit alpha 2

Gene summary

Predicted to enable unfolded protein binding activity. Predicted to be involved in protein targeting to membrane. Predicted to be located in nucleus. Predicted to be part of nascent polypeptide-associated complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

NACAL

MANE transcript

NM_199290.4

Inheritance

—

ClinVar variants

U:29

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr17:61,590,421-61,591,219

External References & Databases

Ensembl (ENSG00000253506)

Transcript & Mutation Effects

hg38 • Region Span ~0.8 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 NACA2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 29

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199290.4. 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						0
missense			29 clinvar			29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	0	0	29

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199290.4	RefSeq	NP_954984.1	1	MANE Select
ENST00000521764.3	Ensembl	ENSP00000427802.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein transport

Cellular Component

nucleus
nascent polypeptide-associated complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000521764
Coding exons: 1
Length: 770
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00242	112	112	0.999	0.00000643	1382
Missense (PolyPhen)		28	24.027	1.1654		347
Synonymous	-1.57	61	47.3	1.29	0.00000322	442
Loss of Function	0.270	2	2.46	0.814	1.07e-7	29

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites) (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.730
RVIS EVS: 0.95
RVIS percentile EVS: 90.01

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.283

Gene Damage Prediction

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