UBAP2L

Chr 1AD

ubiquitin associated protein 2 like

Also known as: NEDLBF, NICE-4, NICE4

UBAP2L encodes a protein that regulates stress granule assembly, recruits ubiquitination machinery to RNA polymerase II for DNA damage response, and is required for proper brain development and neocortex lamination. Mutations cause autosomal recessive neurodevelopmental disorders affecting brain development. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical SummaryUBAP2L
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
7 unique Pathogenic / Likely Pathogenic· 37 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 7.02
OE 0.03 (0.010.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.34Z-score
OE missense 0.62 (0.570.68)
382 obs / 615.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.03 (0.010.10)
00.351.4
Missense OE0.62 (0.570.68)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 2 / 61.4Missense obs/exp: 382 / 615.4Syn Z: -0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateUBAP2L-related neurodevelopmental disorderOTHERAD
DN
0.2399th %ile
GOF
0.1999th %ile
LOF
0.86top 5%

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

LOFprediction above median · 57% of P/LP variants are LoF · LOEUF 0.10

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

100 submitted variants in ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic4
VUS37
Likely Benign6
3
Pathogenic
4
Likely Pathogenic
37
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
2
0
3
Likely Pathogenic
3
0
0
1
4
VUS
2
34
1
0
37
Likely Benign
0
4
0
2
6
Benign
0
0
0
0
0
Total6383350

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

View in ClinVar →

Protein Context — Lollipop Plot

UBAP2L · 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.

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Clinical Literature
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