UBAP2L

Chr 1AD

ubiquitin associated protein 2 like

Also known as: NEDLBF, NICE-4, NICE4

NCBI Gene: 9898 ENSG00000143569 UniProt: Q14157 OMIM: 616472

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida; positive regulation of stress granule assembly; and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.101 OMIM phenotype

Clinical Summary— UBAP2L

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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.

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ClinVar Variants

15 unique Pathogenic / Likely Pathogenic· 120 VUS of 202 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 7.02

OE 0.03 (0.01–0.10)

Highly constrained

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

Missense Constraint?

3.34Z-score

OE missense 0.62 (0.57–0.68)

382 obs / 615.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.10)

0≤0.351.4

Missense OE?0.62 (0.57–0.68)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 2 / 61.4Missense obs/exp: 382 / 615.4Syn Z: -0.11

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateUBAP2L-related neurodevelopmental disorderOTHERAD

This gene — mechanism propensity

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 · 87% 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

202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic7

VUS120

Likely Benign11

Benign4

Conflicting2

Pathogenic

Likely Pathogenic

120

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	0	1	0	8
Likely Pathogenic	6	0	0	1	7
VUS	4	113	2	1	120
Likely Benign	0	6	0	5	11
Benign	0	1	1	2	4
Conflicting	—				2
Total	17	120	4	9	152

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap UBAP2L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →