LPIN2

Chr 18

lipin 2

Also known as: CRMO1, MJDS

The protein acts as a magnesium-dependent phosphatidate phosphatase that converts phosphatidic acid to diacylglycerol during triglyceride and phospholipid biosynthesis, and also functions as a nuclear transcriptional coactivator modulating lipid metabolism. Mutations cause Majeed syndrome, an autosomal recessive disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and neutrophilic dermatosis. The gene is highly constrained against loss-of-function variants (LOEUF 0.51), indicating that complete loss of protein function is likely not tolerated.

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

Majeed syndromeMIM #609628
0
Active trials
5
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.51
LOEUF
Mechanism
Clinical SummaryLPIN2
🧬
Gene-Disease Validity (ClinGen)
Majeed syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 192 VUS of 500 total submissions
📖
GeneReview available — LPIN2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.000
Z-score 4.33
OE 0.34 (0.230.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.98Z-score
OE missense 0.88 (0.810.95)
431 obs / 492.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.230.51)
00.351.4
Missense OE0.88 (0.810.95)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 17 / 50.0Missense obs/exp: 431 / 492.4Syn Z: -1.14

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic12
VUS192
Likely Benign202
Benign29
Conflicting10
42
Pathogenic
12
Likely Pathogenic
192
VUS
202
Likely Benign
29
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
36
0
42
Likely Pathogenic
10
0
2
0
12
VUS
0
159
27
6
192
Likely Benign
0
1
102
99
202
Benign
0
0
29
0
29
Conflicting
10
Total16160196105487

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

View in ClinVar →

Protein Context — Lollipop Plot

LPIN2 · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC