NKTR

protein-coding

natural killer cell triggering receptor, the group of Cyclophilin peptidylprolyl isomerases

Gene summary

This gene encodes a membrane-anchored protein with a hydrophobic amino terminal domain and a cyclophilin-like PPIase domain. It is present on the surface of natural killer cells and facilitates their binding to targets. Its expression is regulated by IL2 activation of the cells. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005385.4

Inheritance

—

ClinVar variants

P:1U:187B:5

Top phenotype

See cases

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr3:42,600,655-42,648,735

External References & Databases

Ensembl (ENSG00000114857)

Transcript & Mutation Effects

hg38 • Region Span ~48.1 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 NKTR variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 180

not providedTotal: 7

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005385.4. 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			1 clinvar	1 clinvar		2
missense			180 clinvar	3 clinvar	1 clinvar	184
nonsense		1 clinvar	4 clinvar			5
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	187	4	1	193

Highest pathogenic variant AF is 6.8441676e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005385.4	RefSeq	NP_005376.2	16	MANE Select
ENST00000232978.13	Ensembl	ENSP00000232978.8	16	MANE Select
NM_001349124.2	RefSeq	NP_001336053.1	16	Standard
NM_001349125.2	RefSeq	NP_001336054.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein peptidyl-prolyl isomerization
protein refolding

Molecular Function

peptidyl-prolyl cis-trans isomerase activity
cyclosporin A binding
unfolded protein binding

Cellular Component

nucleoplasm
mitochondrion
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000232978
Coding exons: 16
Length: 48122
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125747
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	661	764	0.865	0.0000398	9579
Missense (PolyPhen)		125	151.1	0.82724		2053
Synonymous	0.436	258	267	0.966	0.0000133	2717
Loss of Function	6.42	15	75.1	0.200	0.00000497	910

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000062	0.000054	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00028	0.00026	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Component of a putative tumor-recognition complex involved in the function of NK cells (PubMed:8421688). {ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:8421688}.;

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.493
RVIS EVS: 0.1
RVIS percentile EVS: 60.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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