LRRC37A2

Chr 17

leucine rich repeat containing 37 member A2

Also known as: LRRC37

NCBI Gene: 474170 ENSG00000238083 UniProt: A6NM11

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.

ResearchSummary from RefSeq

Predicted to enable ATP binding activity; ATP hydrolysis activity; and metal ion binding activity. Predicted to be involved in SNARE complex disassembly and protein transport. Predicted to be located in cytoplasm and membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.04

Clinical Summary— LRRC37A2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

37 unique Pathogenic / Likely Pathogenic· 452 VUS of 829 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.44

OE 0.66 (0.44–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.38Z-score

OE missense 1.06 (0.97–1.16)

328 obs / 309.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.44–1.04)

0≤0.351.4

Missense OE?1.06 (0.97–1.16)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 14 / 21.1Missense obs/exp: 328 / 309.4Syn Z: 0.05

This gene — mechanism propensity

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

829 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic17

VUS452

Likely Benign230

Benign59

Conflicting21

Pathogenic

Likely Pathogenic

452

VUS

230

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	15	5	0	0	20
Likely Pathogenic	9	8	0	0	17
VUS	9	426	13	4	452
Likely Benign	0	30	92	108	230
Benign	1	10	37	11	59
Conflicting	—				21
Total	34	479	142	123	799

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap LRRC37A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →