UBXN7

Chr 3

UBX domain protein 7

Also known as: UBXD7

NCBI Gene: 26043 ENSG00000163960 UniProt: O94888 OMIM: 616379

This protein functions as a ubiquitin-binding adapter that links cullin ring ligases to the VCP/p97 segregase complex to regulate protein turnover through the ubiquitin-proteasome system. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene is highly constrained against loss-of-function mutations in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; ubiquitin binding activity; and ubiquitin protein ligase binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in nucleoplasm. Part of VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.12

Clinical Summary— UBXN7

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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

34 VUS of 42 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?

0.12LOEUF

pLI 1.000

Z-score 4.70

OE 0.00 (0.00–0.12)

Highly constrained

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

Missense Constraint?

3.18Z-score

OE missense 0.46 (0.40–0.53)

126 obs / 274.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.12)

0≤0.351.4

Missense OE?0.46 (0.40–0.53)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 25.7Missense obs/exp: 126 / 274.3Syn Z: -0.11

This gene — mechanism propensity

0.3892th %ile

GOF

0.2995th %ile

LOF

0.70top 10%

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

LOFprediction above median · LOEUF 0.12

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

42 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	33	34
Likely Benign	0	0	0
Benign	0	0	0
Total	1	33	34

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

View in ClinVar →

87 pathogenic / likely-pathogenic (of 110) ClinVar copy-number / structural variants overlap UBXN7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →