LRRC37A2

Chr 17

leucine rich repeat containing 37 member A2

Also known as: LRRC37

The protein is predicted to have ATP binding and hydrolysis activity and to be involved in SNARE complex disassembly and protein transport in the cytoplasm and membranes. This gene shows extremely low constraint against loss-of-function variants (pLI near 0, LOEUF ~1), suggesting it may tolerate such variants without causing disease. No established disease associations have been reported for mutations in this gene.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 1.04
Clinical SummaryLRRC37A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 65 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.44
OE 0.66 (0.441.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.38Z-score
OE missense 1.06 (0.971.16)
328 obs / 309.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.441.04)
00.351.4
Missense OE1.06 (0.971.16)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 14 / 21.1Missense obs/exp: 328 / 309.4Syn Z: 0.05
DN
0.78top 25%
GOF
0.6149th %ile
LOF
0.2678th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

100 submitted variants in ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic1
VUS65
Likely Benign25
Benign4
Conflicting2
3
Pathogenic
1
Likely Pathogenic
65
VUS
25
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
2
0
3
Likely Pathogenic
0
0
1
0
1
VUS
0
64
1
0
65
Likely Benign
0
8
7
10
25
Benign
0
0
4
0
4
Conflicting
2
Total1721510100

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

View in ClinVar →

Protein Context — Lollipop Plot

LRRC37A2 · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC