NPAT

protein-coding

nuclear protein, coactivator of histone transcription

Gene summary

Enables transcription coactivator activity and transcription corepressor activity. Involved in cell cycle G1/S phase transition and positive regulation of transcription by RNA polymerase II. Located in Cajal body; Gemini of Cajal bodies; and cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_002519.3

Inheritance

ClinVar variants

U:1507B:755

Top phenotype

Nodular lymphocyte predominant Hodgkin lymphoma, familial

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr11:108,155,280-108,222,638

External References & Databases

Ensembl (ENSG00000149308)

Transcript & Mutation Effects

hg38 • Region Span ~67.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colorectal cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005575

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Nodular lymphocyte predominant Hodgkin lymphoma, familialAD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Individuals have been described as being at risk of nodular lymphocyte predominant Hodgkin lymphoma, and awareness may allow early disease detection and managament

Refs: 21562039; 21778346

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NPAT variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 2096

not providedTotal: 568

NPAT-related disorderTotal: 4

Familial colorectal cancer type XTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002519.3. 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			6 clinvar	673 clinvar		679
missense			1484 clinvar	79 clinvar	3 clinvar	1566
nonsense			3 clinvar			3
start loss						0
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	1507	752	3	2262

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002519.3	RefSeq	NP_002510.2	18	MANE Select
ENST00000278612.9	Ensembl	ENSP00000278612.8	18	MANE Select
NM_001321307.1	RefSeq	NP_001308236.1	18	Standard
ENST00000527296.1	Ensembl	ENSP00000436510.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinoblastoma (RB) in Cancer

Biological Process

regulation of transcription involved in G1/S transition of mitotic cell cycle
regulation of gene expression
positive regulation of transcription, DNA-templated
negative regulation of nucleic acid-templated transcription

Molecular Function

transcription coactivator activity
transcription corepressor activity
protein binding
protein C-terminus binding
protein N-terminus binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
Cajal body
Gemini of coiled bodies

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000278612
Coding exons: 18
Length: 65428
Individuals with no LoFs: 124747
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 124796
p: 0.000196

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.146	726	715	1.02	0.0000356	9345
Missense (PolyPhen)		165	202.4	0.81522		2754
Synonymous	-0.264	262	257	1.02	0.0000131	2807
Loss of Function	5.35	13	56.4	0.231	0.00000275	760

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00081	0.00079	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00023	0.00023	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters. {ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:12665581, ECO:0000269|PubMed:12724424, ECO:0000269|PubMed:14585971, ECO:0000269|PubMed:14612403, ECO:0000269|PubMed:15555599, ECO:0000269|PubMed:15988025, ECO:0000269|PubMed:16131487, ECO:0000269|PubMed:17163457, ECO:0000269|PubMed:17826007, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:17974976, ECO:0000269|PubMed:9472014}.;

Recessive Scores

pRec: 0.258

Intolerance Scores

LoFtool: 0.642
RVIS EVS: 0.63
RVIS percentile EVS: 83.58

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.902

Gene Damage Prediction

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