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Intellectual disability

Gene: LRRC32

Amber List (moderate evidence)
LRRC32 (leucine rich repeat containing 32)
EnsemblGeneIds (GRCh38): ENSG00000137507
EnsemblGeneIds (GRCh37): ENSG00000137507
OMIM: 137207, Gene2Phenotype
LRRC32 is in 5 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now more than 3 unrelated individuals with 3 different homozygous LRRC32 variants and syndromic ID/GDD. Hence, this gene should be promoted to Green on Intellectual disability at the next update.
Created: 10 Apr 2026, 9:53 a.m. | Last Modified: 14 Apr 2026, 1:42 p.m.
Panel Version: 9.378
PMID: 40721351 Shboul et al., 2025
Patient 4 - female fetus, Jordanian ancestry, parents first degree consanguineous; homozygous for LRRC32:c.1630C>T, p.Arg544* mutation; presented with growth delay at 18 weeks gestation; fetal growth retardation, oligohydramnios in addition to both lateral ventricle dilatation and right renal pelvis dilation with ventricular septal defect. At 28 weeks GA, the fetus was terminated - normal female with no external gross anomalies detected. Same variant as in PMID: 30976112 (2 Palestinian families).

https://doi.org/10.1016/j.rare.2025.100101 Kumari et al., 2025
Report of a male proband, Pakistani origin, consanguineous parents. He was homozygous for a stop-gain variant in LRRC32 c.1261C>T (p.Arg421*) - confirmed in trans. Variant is rare in gnomAD v4 (MAF = 0.00004464), no homozygotes. Patient presented with cleft palate, proliferative retinopathy (corneal clouding, congenital blindness), and global developmental delay. He also had extremely dry, scaly skin.
Created: 10 Apr 2026, 9:51 a.m. | Last Modified: 10 Apr 2026, 9:51 a.m.
Panel Version: 9.370

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074

Publications

  • 40721351
  • https://doi.org/10.1016/j.rare.2025.100101

Created: 10 Apr 2026, 9:51 a.m.
Last Modified: 14 Apr 2026, 1:42 p.m.
Panel version: 9.370

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

As reviewed by Hannah Knight, PMID:35656379 reported a homozygous LRRC32 variant (c.1354 G > A/ p.Glu452Lys) in a 15-year-old male with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy. This variant is different from the previously reported c.1630C>T/ p.Arg544Ter variant (suggested to be founder variant from haplotype analysis) that was reported in two unrelated families with global developmental delay, cleft palate, and proliferative retinopathy (PMID:30976112).

This gene has already been associated with relevant phenotypes in OMIM (MIM #619074), but not yet in Gene2Phenotype.
Created: 20 Feb 2024, 3:05 p.m. | Last Modified: 20 Feb 2024, 3:05 p.m.
Panel Version: 5.451

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074

Publications

Created: 20 Feb 2024, 3:05 p.m.
Last Modified: 20 Feb 2024, 3:05 p.m.
Panel version: 5.451

Hannah Knight (NIHR BioResource - University of Cambridge)

I don't know

Second report of this disorder describes "a patient who presented with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy. Whole exome sequencing (WES) revealed a very rare homozygous missense variant in the LRRC32 gene, which resulted in substitution of a highly conserved isoleucine to threonine"
Created: 31 Jan 2024, 5:50 p.m. | Last Modified: 31 Jan 2024, 5:50 p.m.
Panel Version: 5.429

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cleft palate, proliferative retinopathy, and developmental delay

Publications

Created: 31 Jan 2024, 5:50 p.m.
Last Modified: 31 Jan 2024, 5:50 p.m.
Panel version: 5.429

Arina Puzriakova (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Rated Red as there is not currently enough evidence that other variants in the LRRC32 gene are disease causing.
Created: 31 Jul 2020, 12:45 p.m. | Last Modified: 31 Jul 2020, 12:45 p.m.
Panel Version: 3.212
Not associated with phenotype in OMIM or G2P.

PMID: 30976112 (2019) - homozygous stop-gain variant in LRRC32 (c.1630C>T; p.Arg544Ter) in three affected individuals from two families with global developmental delay, cleft palate, and proliferative retinopathy. In one family developmental quotient (DQ) varied from borderline low in the female (DQ = 72 at 3 years-2 months) to severely delayed in the male (DQ = 57 at 2 years-11 months). The male in the second family was even more severely delayed (DQ = 23 at 3 years-3 months).

Haplotype analysis indicates a founder effect, and therefore further cases are required to substantiate causation (added founder-effect tag).
Created: 31 Jul 2020, 12:43 p.m. | Last Modified: 31 Jul 2020, 12:45 p.m.
Panel Version: 3.212

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Global developmental delay; Speech delay; Hypotonia; Cleft palate; Proliferative retinopathy

Publications

Created: 31 Jul 2020, 12:43 p.m.
Last Modified: 31 Jul 2020, 12:45 p.m.
Panel version: 3.211

Zornitza Stark (Australian Genomics)

I don't know

Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Created: 1 May 2020, 10:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; cleft palate; proliferative retinopathy

Publications

Created: 1 May 2020, 10:19 a.m.

Panel version: 3.33

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074
Tags
founder-effect Q2_26_promote_green
OMIM
137207
Clinvar variants
Variants in LRRC32
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Apr 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: LRRC32 were set to 30976112; 35656379

10 Apr 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: lrrc32 has been classified as Amber List (Moderate Evidence).

10 Apr 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q2_26_promote_green tag was added to gene: LRRC32.

20 Feb 2024, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: lrrc32 has been classified as Amber List (Moderate Evidence).

20 Feb 2024, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: LRRC32 were set to 30976112

9 Jun 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074

31 Jul 2020, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag founder-effect tag was added to gene: LRRC32.

31 Jul 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: lrrc32 has been classified as Red List (Low Evidence).

1 May 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: LRRC32 was added gene: LRRC32 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC32 were set to 30976112 Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy Review for gene: LRRC32 was set to AMBER