Proteinuric renal disease

Gene: LAMA5

Green List (high evidence)

Comment on list classification: There are now more than 3 unrelated patients reported in literature with biallelic LAMA5 variants and renal disease (either steroid-resistant nephrotic syndrome or infantile nephrotic syndrome), including severe early-onset proteinuria. Hence, this gene can be promoted to Green at the next update.

Created: 26 Oct 2026, 2:39 p.m. | Last Modified: 26 Oct 2026, 2:40 p.m.

Panel Version: 6.24

PMID: 35419533 Taniguchi et al., 2021
Report of 4 Japanese patients: three patients from 2 families with LAMA5 gene biallelic truncating variants manifesting infantile nephrotic syndrome, and one patient with steroid-resistant nephrotic syndrome habrouring biallelic LAMA5 missense variants. Seq method: NGS sequencing of 62 podocyte-related genes in a large cohort with severe proteinuria. All 4 patients presented with proteinuria within 6 months of age.

PMID: 36714636 Sunwoo et al., 2023
Case report: patient with infantile steroid-resistant nephrotic syndrome and comp het LAMA5 variants: c.3434G > A, p.Cys1145Tyr and c.6883C > T, p.Gln2295*. Proband is a female who presented at 10-months-old with eyelid edema and massive proteinuria without any extrarenal symptoms or family history. Renal biopsy revealed focal segmental glomerulosclerosis with widely effaced epithelial foot processes and a "moth-eaten" appearance. She progressed to end stage kidney disease, requiring dialysis at 31 months of age, and underwent a deceased-donor kidney transplant at 6 years of age.

PMID: 37985485 Deepthi et al., 2024
Report of a two-and-a-half-month-old female infant who presented with generalized edema for 10 days. She was comp het for LAMA5 variants c.385C>A, p.Gln129Lys & c.3932_3936dup, p.Phe1313Profs*44 (confirmed in trans). She was diagnosed with Congenital Nephrotic Syndrome and died at 6 months of age. Kidney biopsy was consistent with diffuse mesangial sclerosis.

LAMA5 association with AR LAMA5-related multisystemic syndrome has been classified as Definitive in ClinGen (Glomerulopathy GCEP, 2022). This gene is associated with AR ?Bent bone dysplasia syndrome 2, OMIM:620076 and AR Nephrotic syndrome, type 26, OMIM:620049. Resources accessed 26th Oct 2026.

Created: 26 Oct 2026, 2:31 p.m. | Last Modified: 26 Oct 2026, 2:56 p.m.

Panel Version: 6.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 26, OMIM:620049; familial nephrotic syndrome, MONDO:0002350

Publications

• 35419533
• 36714636
• 37985485

I don't know

Three further families published this year, though note the authors refer to the variants as VOUS.

Created: 8 Aug 2019, 4:28 a.m. | Last Modified: 8 Aug 2019, 4:28 a.m.

Panel Version: 1.221

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome

Publications

• 29534211

Red List (low evidence)

Comment on list classification: Changing the rating of this gene to Amber. 3 cases with homozygous missense variants reported but authors classify as VUS as there is no experimental evidence to link the impact of these genetic variants on protein function to disease pathogenesis.

Created: 9 Oct 2019, 10:57 a.m. | Last Modified: 9 Oct 2019, 10:57 a.m.

Panel Version: 1.223

Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. There is evolutionary conservation at these sites. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.

Created: 14 Aug 2019, 4:31 p.m. | Last Modified: 14 Aug 2019, 4:39 p.m.

Panel Version: 1.221

This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: LAMA5; Suggested initial gene rating: red; Evidence for inclusion: PMID: 29534211; Other comments: One published patient with paediatric nephrotic syndrome and VUS in LAMA5, plus one possible case (unpublished) identified by nephrotic syndrome research group (personal communication).

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
No OMIM disease association

Publications

• PMID: 29534211