UBR7

Chr 14AR

ubiquitin protein ligase E3 component n-recognin 7

Also known as: C14orf130, LICAS

NCBI Gene: 55148 ENSG00000012963 UniProt: Q8N806 OMIM: 613816

The protein is an E3 ubiquitin ligase that recognizes and targets proteins with destabilizing N-terminal residues for ubiquitination and proteasomal degradation as part of the N-end rule pathway. Biallelic mutations cause Li-Campeau syndrome, an autosomal recessive disorder. The gene shows significant constraint against loss-of-function variants (LOEUF 0.447), indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a UBR box-containing protein that belongs to the E3 ubiquitin ligase family. The protein also contains a plant homeodomain (PHD) in the C-terminus. In mammals, the encoded protein recognizes N-degrons, the destabilizing N-terminal residues of short-lived proteins, which results in ubiquitinylation, and proteolysis via the proteasome. [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.451 OMIM phenotype

Clinical Summary— UBR7

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 35 VUS of 67 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.494

Z-score 3.54

OE 0.21 (0.11–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.85Z-score

OE missense 0.65 (0.57–0.75)

145 obs / 222.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.11–0.45)

0≤0.351.4

Missense OE?0.65 (0.57–0.75)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 5 / 23.5Missense obs/exp: 145 / 222.6Syn Z: 1.04

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic3

VUS35

Likely Benign9

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	0	1	0	6
Likely Pathogenic	3	0	0	0	3
VUS	1	34	0	0	35
Likely Benign	0	5	0	4	9
Benign	0	0	0	0	0
Conflicting	—				1
Total	9	39	1	4	54

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap UBR7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →