UBQLN4

Chr 1

ubiquilin 4

Also known as: A1U, A1Up, C1orf6, CIP75, UBIN

NCBI Gene: 56893 ENSG00000160803 UniProt: Q9NRR5 OMIM: 605440

Enables K48-linked polyubiquitin modification-dependent protein binding activity and identical protein binding activity. Involved in DNA damage response; negative regulation of double-strand break repair via homologous recombination; and regulation of catabolic process. Located in several cellular components, including autophagosome; proteasome complex; and site of DNA damage. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— UBQLN4

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 58 VUS of 75 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.983

Z-score 4.13

OE 0.12 (0.05–0.30)

Highly constrained

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

Missense Constraint?

2.88Z-score

OE missense 0.56 (0.50–0.64)

196 obs / 347.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.30)

0≤0.351.4

Missense OE?0.56 (0.50–0.64)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 3 / 25.6Missense obs/exp: 196 / 347.0Syn Z: 1.33

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS58

Likely Benign4

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	0	0	0
VUS	0	58	0	58
Likely Benign	0	1	3	4
Benign	0	2	1	3
Total	1	61	4	66

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap UBQLN4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →