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Intellectual disability

Gene: LRRC45

Amber List (moderate evidence)
LRRC45 (leucine rich repeat containing 45)
EnsemblGeneIds (GRCh38): ENSG00000169683
EnsemblGeneIds (GRCh37): ENSG00000169683
LRRC45 is in 3 panels

1 review

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are 5 individuals form 4 unrelated families reported in literature with biallelic variants in LRRC45. 2/5 patients did not live beyond 3 months of age. In remaining 3 cases, 3/3 presented with severe developmental delay, delayed milestone attainment, and intellectual disability (severity not stated). Based on available evidence, this gene should be promoted to Green for Intellectual disability at the next GMS update.
Created: 11 Nov 2025, 12:02 p.m. | Last Modified: 11 Nov 2025, 12:02 p.m.
Panel Version: 9.165
PMID: 34716235 Best et al., 2022
2 unrelated individuals with LP biallelic variants in LRRC45.
Proband 1 (CMC Patient 48): Bardet-Biedl syndrome-like multi-systemic ciliopathy - homozygous for NM_144999.4: c.1074_1075insTG, p.(Leu359CysfsTer19), also homozygous for CFAP45 (CCDC19) NM_012337.3: c.433C>T, p.(Arg145Ter).
Sibling with developmental delay and ID was homozygous for the LRRC45 variant, did not harbour the CFAP45 mutation (proposed to account for the ciliopathy phenotype); parents confirmed as het for each.
Proband 2: presented with cone-rod dystrophy (possible ciliopathy basis) - compound het: NM_144999.4: c.1A>T, p.Met1? & NM_144999.4: c.1126–1G>A. Singleton case.

PMID: 39638757 Radhakrishnan et al., 2025
Report of 3 individuals from 2 unrelated families with severe central nervous system anomalies, harbouring biallelic variants in LRRC45: P1: c.1402-2A>G; P2 and P3: c.1262G>C (p.Arg421Thr). Method: Exome seq.
P1 - female, onset at 1yr 8months, Indian origin, presented with febrile seizures and developmental delay, severe brain anomalies. At 3yr 7 mo: titubation, nystagmus, axial and peripheral hypotonia, normal deep tendon reflexes and pes planus.
P2 & 3 - born to Turkish consanguineous parents; P2 - female, presented with severe muscular hypotonia, respiratory insufficiency, and apnea bradycardia syndrome; ophthalmological exam was normal; patient died at 3 months old. P3 - male fetus, pregnancy terminated.
Functional evidence - P1 fibroblasts - variant c.1402-2A>G shown to result in a transcript lacking exon 14 (total 17 exons); LRRC45 mRNA and protein levels significantly reduced; significant reduction of primary cilia frequency and length.
c.1402-2A>G - splice acceptor - MAF 0.0001647 (South Asian population, 14 heterozygotes - gnomAD v4.1).
c.1262G>C (p.Arg421Thr) - MAF 8.475e-7 (1 het in European pop - gnomAD v4.1); Revel score =
Uncertain (0.31).

Functional evidence:
PMID: 30131441 Kurtulmus et al., 2018 - LRRC45 shown to be associated with the basal body of primary and motile cilia in both differentiated and stem cells - broad function in ciliogenesis.

This gene is not yet associated with a disease in OMIM (accessed 11th Nov 2025).
Sources: Other
Created: 11 Nov 2025, 11:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ciliopathy, MONDO:0005308; Abnormal brain morphology, HP:0012443; neurodevelopmental disorder, MONDO:0700092

Publications

Created: 11 Nov 2025, 11:56 a.m.

Panel version: 9.165

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • ciliopathy, MONDO:0005308
  • Abnormal brain morphology, HP:0012443
  • neurodevelopmental disorder, MONDO:0700092
Tags
Q4_25_promote_green
Clinvar variants
Variants in LRRC45
Penetrance
None
Publications
Panels with this gene

History Filter Activity

11 Nov 2025, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q4_25_promote_green tag was added to gene: LRRC45.

11 Nov 2025, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: lrrc45 has been classified as Amber List (Moderate Evidence).

11 Nov 2025, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ida Ertmanska (Genomics England Curator)

gene: LRRC45 was added gene: LRRC45 was added to Intellectual disability. Sources: Other Mode of inheritance for gene: LRRC45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC45 were set to 30131441; 34716235; 39638757 Phenotypes for gene: LRRC45 were set to ciliopathy, MONDO:0005308; Abnormal brain morphology, HP:0012443; neurodevelopmental disorder, MONDO:0700092 Review for gene: LRRC45 was set to AMBER