LARP4B

Chr 10

La ribonucleoprotein 4B

Also known as: KIAA0217, LARP5

This gene encodes a cytoplasmic protein that stimulates mRNA translation through its La motif and RNA recognition motifs. Mutations cause autosomal recessive intellectual disability with developmental delay and microcephaly, typically presenting in early childhood. LARP4B is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal neurodevelopment.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
34
P/LP submissions
3%
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryLARP4B
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 112 VUS of 193 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 5.55
OE 0.05 (0.020.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.94Z-score
OE missense 0.74 (0.680.81)
326 obs / 440.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.020.16)
00.351.4
Missense OE0.74 (0.680.81)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 2 / 39.8Missense obs/exp: 326 / 440.7Syn Z: -0.03
DN
0.3196th %ile
GOF
0.2994th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

193 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic3
VUS112
Likely Benign16
Benign3
31
Pathogenic
3
Likely Pathogenic
112
VUS
16
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
1
2
0
3
VUS
1
96
15
0
112
Likely Benign
0
10
5
1
16
Benign
0
0
1
2
3
Total1107543165

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

View in ClinVar →

Protein Context — Lollipop Plot

LARP4B · 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
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗