LRRC34

Chr 3

leucine rich repeat containing 34

NCBI Gene: 151827 ENSG00000171757 UniProt: Q8IZ02

Predicted to be involved in cell differentiation. Predicted to act upstream of or within gene expression and telomere maintenance. Predicted to be located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.00

Clinical Summary— LRRC34

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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

65 VUS of 81 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?

1.00LOEUF

pLI 0.000

Z-score 1.57

OE 0.63 (0.41–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.87–1.08)

225 obs / 232.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.41–1.00)

0≤0.351.4

Missense OE?0.97 (0.87–1.08)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 13 / 20.7Missense obs/exp: 225 / 232.9Syn Z: 0.61

This gene — mechanism propensity

0.6258th %ile

GOF

0.6541th %ile

LOF

0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

81 submitted variants in ClinVar

ClinVar

Classification Summary

VUS65

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	2	63	65
Likely Benign	0	4	4
Benign	0	0	0
Total	2	67	69

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap LRRC34 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →