LRRC14B

Chr 5

leucine rich repeat containing 14B

NCBI Gene: 389257ENSG00000185028UniProt: A6NHZ5OMIM: 619368

This gene encodes a leucine-rich repeat containing protein that is a member of the PRAME family. Mutations cause autosomal recessive primary microcephaly with simplified gyral pattern, intellectual disability, and seizures, typically presenting in infancy. The gene shows minimal constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIMResearchSummary from RefSeq
GOFmechanismLOEUF 1.73
Clinical Summary— LRRC14B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
130 unique Pathogenic / Likely Pathogenic· 127 VUS of 277 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.73LOEUF
pLI 0.000
Z-score -0.37
OE 1.12 (0.72–1.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.12Z-score
OE missense 0.98 (0.89–1.08)
306 obs / 312.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.12 (0.72–1.73)
0≤0.351.4
Missense OE0.98 (0.89–1.08)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 13 / 11.6Missense obs/exp: 306 / 312.2Syn Z: -0.01
DN
0.5869th %ile
GOF
0.6833th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

277 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic128
Likely Pathogenic2
VUS127
Likely Benign16
Benign2
128
Pathogenic
2
Likely Pathogenic
127
VUS
16
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
128
0
128
Likely Pathogenic
0
0
2
0
2
VUS
0
104
23
0
127
Likely Benign
0
6
10
0
16
Benign
0
1
1
0
2
Total01111640275

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

View in ClinVar →

Protein Context — Lollipop Plot

LRRC14B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients