LRP12

Chr 8AD

LDL receptor related protein 12

Also known as: ALS28, MIG13A, ST7

NCBI Gene: 29967 ENSG00000147650 UniProt: Q9Y561 OMIM: 618299

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the low-density lipoprotein receptor related protein family. The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

OMIM ResearchGenerating clinical summary…

ADLOEUF 0.262 OMIM phenotypes

Clinical Summary— LRP12

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Gene-Disease Validity (ClinGen)

oculopharyngodistal myopathy 1 · ADModerate

Moderate evidence — consider for supplementary testing

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 106 VUS of 129 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.998

Z-score 4.92

OE 0.11 (0.05–0.26)

Highly constrained

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

Missense Constraint?

1.30Z-score

OE missense 0.83 (0.77–0.90)

397 obs / 477.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.26)

0≤0.351.4

Missense OE?0.83 (0.77–0.90)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 4 / 35.8Missense obs/exp: 397 / 477.2Syn Z: -0.90

ClinVar Variant Classifications

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS106

Likely Benign6

Benign2

Conflicting1

Pathogenic

106

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	105	0	0	106
Likely Benign	0	3	0	3	6
Benign	0	1	1	0	2
Conflicting	—				1
Total	1	109	2	3	116

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap LRP12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →