LRRCC1

protein-coding

leucine rich repeat and coiled-coil centrosomal protein 1

Gene summary

This gene encodes a centrosomal protein that maintains the structural integrity of the centrosome and plays a key role in mitotic spindle formation. The encoded protein contains an N-terminal leucine-rich repeat domain and a C-terminal coiled-coil domain. It associates with the centrosome throughout the cell cycle and accumulates on the mitotic centrosome. [provided by RefSeq, Mar 2017]

MANE transcript

NM_033402.5

Inheritance

—

ClinVar variants

P:1U:158B:52

Top phenotype

Joubert syndrome and related disorders

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr8:85,107,215-85,146,080

External References & Databases

Ensembl (ENSG00000133739)

Transcript & Mutation Effects

hg38 • Region Span ~38.9 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 LRRCC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 141

not providedTotal: 98

Joubert syndrome and related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033402.5. 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				23 clinvar	2 clinvar	25
missense			147 clinvar	20 clinvar	7 clinvar	174
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		10 clinvar			11
Total	1	0	158	43	9	211

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033402.5	RefSeq	NP_208325.3	19	MANE Select
ENST00000360375.8	Ensembl	ENSP00000353538.3	19	MANE Select
NM_001349636.2	RefSeq	NP_001336565.1	18	Standard
NM_001349637.2	RefSeq	NP_001336566.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle
cell division

Cellular Component

cytoplasm
centrosome
centriole

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360375
Coding exons: 19
Length: 38930
Individuals with no LoFs: 124655
Homozygous LoFs: 1
Heterozygous LoFs: 130
Defined: 124786
p: 0.000525

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.109	487	494	0.986	0.0000237	6858
Missense (PolyPhen)		72	98.197	0.73322		1494
Synonymous	0.226	168	172	0.978	0.00000881	1757
Loss of Function	1.76	39	52.8	0.739	0.00000262	717

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00078	rare
Latino/Admixed American	0.00094	0.00084	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00069	0.00067	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00054	0.00052	rare
South Asian	0.00043	0.00039	rare
Other	0.00086	0.00083	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for the organization of the mitotic spindle. Maintains the structural integrity of centrosomes during mitosis. {ECO:0000269|PubMed:18728398}.;

Recessive Scores

pRec: 0.0964

Intolerance Scores

LoFtool: 0.964
RVIS EVS: 1.89
RVIS percentile EVS: 97.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00472

Gene Damage Prediction

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