KLRC1

protein-coding

killer cell lectin like receptor C1, the group of CD molecules|Killer cell lectin like receptors|C-type lectin domain containing

Gene summary

Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor family, also called NKG2 family, which is a group of transmembrane proteins preferentially expressed in NK cells. This family of proteins is characterized by the type II membrane orientation and the presence of a C-type lectin domain. This protein forms a complex with another family member, KLRD1/CD94, and has been implicated in the recognition of the MHC class I HLA-E molecules in NK cells. The genes of NKG2 family members form a killer cell lectin-like receptor gene cluster on chromosome 12. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jan 2015]

Previous symbols:

NKG2

MANE transcript

NM_002259.5

Inheritance

—

ClinVar variants

U:23B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr12:10,442,264-10,454,685

External References & Databases

Ensembl (ENSG00000134545)

Transcript & Mutation Effects

hg38 • Region Span ~12.4 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 KLRC1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 23

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002259.5. 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			21 clinvar	2 clinvar		23
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	23	2	0	25

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002259.5	RefSeq	NP_002250.2	6	MANE Select
ENST00000359151.8	Ensembl	ENSP00000352064.3	6	MANE Select
NM_001304448.1	RefSeq	NP_001291377.1	7	Standard
NM_007328.4	RefSeq	NP_015567.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Graft-versus-host disease - Homo sapiens (human)
Natural killer cell mediated cytotoxicity - Homo sapiens (human)
ras-independent pathway in nk cell-mediated cytotoxicity
Immune System

Biological Process

cell surface receptor signaling pathway
regulation of immune response

Molecular Function

transmembrane signaling receptor activity
protein binding
MHC class I protein complex binding
carbohydrate binding
protein antigen binding

Cellular Component

plasma membrane
integral component of plasma membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000544822
Coding exons: 6
Length: 12422
Individuals with no LoFs: 125693
Homozygous LoFs: 1
Heterozygous LoFs: 24
Defined: 125718
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0721	122	120	1.02	0.00000581	1520
Missense (PolyPhen)		29	27.178	1.067		394
Synonymous	0.675	36	41.5	0.867	0.00000200	428
Loss of Function	0.844	8	11.0	0.726	5.62e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0012	notable
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)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells.;

Recessive Scores

pRec: 0.191

Intolerance Scores

LoFtool: 0.978
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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