LRRC14

protein-coding

leucine rich repeat containing 14

Gene summary

This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

MANE transcript

NM_014665.4

Inheritance

—

ClinVar variants

U:71B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr8:144,517,992-144,525,172

External References & Databases

Ensembl (ENSG00000160959)

Transcript & Mutation Effects

hg38 • Region Span ~7.2 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 LRRC14 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014665.4. 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			2 clinvar			2
missense			69 clinvar	3 clinvar		72
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	71	3	0	74

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014665.4	RefSeq	NP_055480.1	3	MANE Select
ENST00000292524.6	Ensembl	ENSP00000292524.1	3	MANE Select
NM_001272036.2	RefSeq	NP_001258965.1	3	Standard
ENST00000525766.1	Ensembl	ENSP00000434738.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of NF-kappaB transcription factor activity
negative regulation of toll-like receptor signaling pathway

Molecular Function

kinase binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000292524
Coding exons: 3
Length: 7182
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125658
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	258	316	0.816	0.0000217	3134
Missense (PolyPhen)		50	83.088	0.60177		920
Synonymous	-2.44	176	139	1.26	0.00000855	1127
Loss of Function	1.48	8	14.0	0.573	7.74e-7	142

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates Toll-like receptor-mediated NF- kappa-B signaling by disrupting IKK core complex formation through interaction with IKBKB. {ECO:0000269|PubMed:27426725}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.594
RVIS EVS: -1
RVIS percentile EVS: 8.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.949

Gene Damage Prediction

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