NASP

protein-coding

nuclear autoantigenic sperm protein, the group of Tetratricopeptide repeat domain containing

Gene summary

This gene encodes a H1 histone binding protein that is involved in transporting histones into the nucleus of dividing cells. Multiple isoforms are encoded by transcript variants of this gene. The somatic form is expressed in all mitotic cells, is localized to the nucleus, and is coupled to the cell cycle. The testicular form is expressed in embryonic tissues, tumor cells, and the testis. In male germ cells, this protein is localized to the cytoplasm of primary spermatocytes, the nucleus of spermatids, and the periacrosomal region of mature spermatozoa. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002482.4

Inheritance

—

ClinVar variants

U:103B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr1:45,583,846-45,618,904

External References & Databases

Ensembl (ENSG00000132780)

Transcript & Mutation Effects

hg38 • Region Span ~35.1 kb

Loading mutation effect viewer...

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 NASP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002482.4. 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			3 clinvar	1 clinvar	1 clinvar	5
missense			92 clinvar	11 clinvar		103
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	103	12	1	116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 116 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002482.4	RefSeq	NP_002473.2	15	MANE Select
ENST00000350030.8	Ensembl	ENSP00000255120.5	15	MANE Select
NM_001195193.2	RefSeq	NP_001182122.1	13	Standard
NM_152298.4	RefSeq	NP_689511.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

G1/S transition of mitotic cell cycle
blastocyst development
DNA replication
DNA replication-dependent nucleosome assembly
DNA replication-independent nucleosome assembly

Molecular Function

protein binding
histone binding

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
cytoplasm
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000350030
Coding exons: 15
Length: 35049
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125746
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.606	368	402	0.915	0.0000193	5114
Missense (PolyPhen)		69	114.09	0.60478		1517
Synonymous	-0.279	151	147	1.03	0.00000776	1495
Loss of Function	4.96	5	38.0	0.131	0.00000162	530

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. {ECO:0000250|UniProtKB:Q99MD9}.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.118
RVIS EVS: -0.18
RVIS percentile EVS: 40.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.982

Gene Damage Prediction

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