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…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic faciesMIM #620494

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in UBAP2L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

1,074 rare PASS variants

Rare truncating (LoF)

1 in 7,200

40 rare PASS variants

Rare synonymous (reference)

1 in 110

538 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UBAP2L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 6,500
South Asian	~43k	1 in 94	1 in 1,500
Remaining (unassigned)	~30k	1 in 79	≈ 1 in 6,100
European (Finnish)	~27k	1 in 210	≈ 1 in 27,000
Admixed American	~22k	1 in 86	1 in 3,900
African / African American	~21k	1 in 93	≈ 1 in 17,000
East Asian	~20k	1 in 100	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 640	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 25 of 26 coding exons well covered in gnomAD exomes; exon 6 poorly covered. Genomes: all 26.? see exons ↓