LRRC45

protein-coding

leucine rich repeat containing 45

Gene summary

Involved in cilium assembly and protein localization to centriolar satellite. Located in centriole; centrosome; and ciliary basal body. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_144999.4

Inheritance

ClinVar variants

P:1U:266B:98

Top phenotype

LRRC45-related disorder

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr17:82,023,305-82,031,151

External References & Databases

Ensembl (ENSG00000169683)

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published PMID: 39638757 – Reports three affected individuals from two unrelated families with a severe neurodevelopmental ciliopathy phenotype due to biallelic LRRC45 variants. Clinical features included global developmental delay, hypotonia, neurological impairment, and structural brain abnormalities consistent with a ciliopathy spectrum. Family 1 – One affected individual. Case-level (biallelic predicted null in AR model; scored once; consanguinity not reported so no deduction applied) = 1.5; segregation = 0; case-control = 0; Family 1 total = 1.5. Family 2 – Two affected siblings from a consanguineous family. Case-level (non-LOF start 0.1; homozygous scored once; consanguinity) = 0.1; segregation (additional affected sibling counted conservatively) = 0.5; case-control = 0; Family 2 total = 0.6. PMID: 39638757 total = 0.7. Published genetic evidence total = 2.1/12 Genetic evidence – Our cases Family 1 – one proband. Case-level (biallelic predicted null in AR model; homozygous scored once; consanguinity unknown so no deduction applied) = 1.5; segregation = 0; case-control = 0; Family 1 total = 1.5. Our cases total = 1.5/12 Total genetic evidence (published + our cases) 2.1 + 1.5 = 3.6/12 Experimental evidence – Published PMID: 39638757 – Functional studies demonstrate that the splice variant causes aberrant splicing with significantly reduced LRRC45 mRNA and protein expression in patient-derived fibroblasts. Additionally, patient cells exhibited reduced primary cilia frequency and shortened cilia length, supporting a ciliogenesis defect consistent with disease mechanism. Functional alteration (patient cells) = 1.0; Gene function / biological plausibility (role in distal appendages and early ciliogenesis) = 0.5; Experimental evidence total = 1.5/6 Overall score Genetic evidence = 4.0 Experimental evidence = 1.5 Overall score = 5.1/18

ciliopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRRC45 variants in ClinVar

4 Conditions Cataloged

LRRC45-related disorderTotal: 328

not specifiedTotal: 120

not providedTotal: 3

LRRC45 associated neurological ciliopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144999.4. 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			3 clinvar	82 clinvar		85
missense			235 clinvar	16 clinvar		251
nonsense			7 clinvar			7
start loss						0
frameshift			9 clinvar			9
splice donor/acceptor (+/-2bp)		1 clinvar	12 clinvar			13
Total	0	1	266	98	0	365

Highest pathogenic variant AF is 0.000011321663

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144999.4	RefSeq	NP_659436.1	17	MANE Select
ENST00000306688.8	Ensembl	ENSP00000306760.3	17	MANE Select
ENST00000577638.1	Ensembl	ENSP00000462276.1	1	Standard
ENST00000581227.1	Ensembl	ENSP00000462928.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

nucleoplasm
centrosome
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306688
Coding exons: 17
Length: 7850
Individuals with no LoFs: 125193
Homozygous LoFs: 0
Heterozygous LoFs: 61
Defined: 125254
p: 0.000244

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	325	381	0.853	0.0000237	4253
Missense (PolyPhen)		80	85.117	0.93988		1017
Synonymous	0.400	160	167	0.961	0.0000101	1337
Loss of Function	2.15	23	37.2	0.619	0.00000185	409

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00031	rare
South Asian	0.00033	0.00020	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the proteinaceous fiber-like linker between two centrioles, required for centrosome cohesion. {ECO:0000269|PubMed:24035387}.;

Intolerance Scores

LoFtool: 0.781
RVIS EVS: -0.51
RVIS percentile EVS: 21.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.469

Gene Damage Prediction

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