NLRC5

protein-coding

NLR family CARD domain containing 5, the group of NLR family

Gene summary

This gene encodes a member of the caspase recruitment domain-containing NLR family. This gene plays a role in cytokine response and antiviral immunity through its inhibition of NF-kappa-B activation and negative regulation of type I interferon signaling pathways. [provided by RefSeq, Oct 2011]

MANE transcript

NM_001384950.1

Inheritance

—

ClinVar variants

U:260B:36

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr16:56,989,485-57,083,531

External References & Databases

Ensembl (ENSG00000140853)

Transcript & Mutation Effects

hg38 • Region Span ~94.0 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 NLRC5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 243

not providedTotal: 73

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001384950.1. 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			7 clinvar	7 clinvar	2 clinvar	16
missense			241 clinvar	25 clinvar	2 clinvar	268
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	260	32	4	296

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001384950.1	RefSeq	NP_001371879.1	47	MANE Select
ENST00000688547.1	Ensembl	ENSP00000509992.1	47	MANE Select
NM_001330552.2	RefSeq	NP_001317481.1	46	Standard
NM_001384951.1	RefSeq	NP_001371880.1	46	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

DDX58/IFIH1-mediated induction of interferon-alpha/beta
Innate Immune System
Immune System
Negative regulators of DDX58/IFIH1 signaling

Biological Process

response to bacterium
negative regulation of NF-kappaB transcription factor activity
negative regulation of type I interferon production
intracellular signal transduction
regulation of kinase activity

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm
centrosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262510
Coding exons: 47
Length: 94047
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.01	837	1.02e+3	0.823	0.0000582	12102
Missense (PolyPhen)		101	185.24	0.54524		2596
Synonymous	0.748	424	444	0.955	0.0000268	3816
Loss of Function	5.90	30	90.6	0.331	0.00000430	1062

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00044	0.00042	rare
European (Non-Finnish)	0.00036	0.00035	rare
South Asian	0.00016	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable regulator of the NF-kappa-B and type I interferon signaling pathways. May also regulate the type II interferon signaling pathway. Plays a role in homeostatic control of innate immunity and in antiviral defense mechanisms. {ECO:0000269|PubMed:20061403, ECO:0000269|PubMed:20434986}.;

Recessive Scores

pRec: 0.0897

Intolerance Scores

RVIS EVS: 0.51
RVIS percentile EVS: 80.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.277

Gene Damage Prediction

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