LAMA1

Chr 18AR

laminin subunit alpha 1

Also known as: LAMA, PTBHS, S-LAM-alpha

This gene encodes the alpha-1 subunit of laminin, an extracellular matrix glycoprotein that mediates cell attachment, migration, and tissue organization during development by binding to cellular receptors including alpha-dystroglycan. Biallelic mutations cause Poretti-Boltshauser syndrome, an autosomal recessive disorder characterized by cerebellar dysplasia and cystic malformation of the posterior fossa. The gene is highly constrained against loss-of-function variants (LOEUF 0.621), reflecting its critical role in nervous system development.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Poretti-Boltshauser syndromeMIM #615960
AR
0
Active trials
23
Pubs (1 yr)
31
P/LP submissions
0%
P/LP missense
0.62
LOEUF
LOF
Mechanism· G2P
Clinical SummaryLAMA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 231 VUS of 400 total submissions
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GeneReview available — LAMA1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.000
Z-score 5.54
OE 0.51 (0.430.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.14Z-score
OE missense 1.01 (0.971.05)
1731 obs / 1715.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.430.62)
00.351.4
Missense OE1.01 (0.971.05)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 78 / 151.6Missense obs/exp: 1731 / 1715.1Syn Z: -1.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLAMA1-related cerebellar dysplasia with cysts with or without retinal dystrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7132th %ile
GOF
0.6931th %ile
LOF
0.2582th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic14
VUS231
Likely Benign102
17
Pathogenic
14
Likely Pathogenic
231
VUS
102
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
7
0
17
Likely Pathogenic
8
0
6
0
14
VUS
1
219
11
0
231
Likely Benign
0
13
39
50
102
Benign
0
0
0
0
0
Total192326350364

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LAMA1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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