LAMA5

Chr 20AR

laminin subunit alpha 5

Also known as: BBDS2, NPHS26

The protein is the alpha-5 subunit of laminin that mediates cell attachment, migration and tissue organization during embryonic development and regulates skeletal development through integrin-mediated signaling. Mutations cause bent bone dysplasia syndrome and nephrotic syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variation (LOEUF 0.31), affecting primarily skeletal and renal systems.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.312 OMIM phenotypes
Clinical SummaryLAMA5
🧬
Gene-Disease Validity (ClinGen)
LAMA5-related multisystemic syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.006
Z-score 9.48
OE 0.24 (0.190.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
-0.27Z-score
OE missense 1.02 (0.981.05)
2301 obs / 2264.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.24 (0.190.31)
00.351.4
Missense OE1.02 (0.981.05)
00.61.4
Synonymous OE1.26
01.21.6
LoF obs/exp: 44 / 182.1Missense obs/exp: 2301 / 2264.6Syn Z: -6.45
DN
0.6840th %ile
GOF
0.6637th %ile
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LAMA5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →