LRP12

Chr 8AD

LDL receptor related protein 12

Also known as: ALS28, MIG13A, ST7

This gene encodes a transmembrane receptor protein involved in internalization of lipophilic molecules and signal transduction. Mutations cause amyotrophic lateral sclerosis 28 and oculopharyngodistal myopathy 1 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.256), indicating intolerance to protein loss.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Amyotrophic lateral sclerosis 28MIM #620452
AD
Oculopharyngodistal myopathy 1MIM #164310
AD
0
Active trials
15
Pubs (1 yr)
40
P/LP submissions
0%
P/LP missense
0.26
LOEUF· LoF intol.
Mechanism
Clinical SummaryLRP12
🧬
Gene-Disease Validity (ClinGen)
oculopharyngodistal myopathy 1 · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 111 VUS of 172 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.998
Z-score 4.92
OE 0.11 (0.050.26)
Highly constrained

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

Missense Constraint
1.30Z-score
OE missense 0.83 (0.770.90)
397 obs / 477.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.050.26)
00.351.4
Missense OE0.83 (0.770.90)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 4 / 35.8Missense obs/exp: 397 / 477.2Syn Z: -0.90

ClinVar Variant Classifications

172 submitted variants in ClinVar

Classification Summary

Pathogenic39
VUS111
Likely Benign6
Benign2
Conflicting1
39
Pathogenic
111
VUS
6
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
0
0
0
VUS
1
103
7
0
111
Likely Benign
0
3
0
3
6
Benign
0
1
1
0
2
Conflicting
1
Total1107473159

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

View in ClinVar →

Protein Context — Lollipop Plot

LRP12 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗