UBR3

Chr 2

ubiquitin protein ligase E3 component n-recognin 3

Also known as: ZNF650

NCBI Gene: 130507 ENSG00000144357 UniProt: Q6ZT12 OMIM: 613831

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including sensory perception of smell; suckling behavior; and ubiquitin-dependent protein catabolic process via the N-end rule pathway. Predicted to act upstream of or within in utero embryonic development and olfactory behavior. Predicted to be located in membrane. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.13

Clinical Summary— UBR3

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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

162 VUS of 208 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 8.25

OE 0.07 (0.04–0.13)

Highly constrained

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

Missense Constraint?

4.43Z-score

OE missense 0.57 (0.52–0.61)

468 obs / 826.2 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.07 (0.04–0.13)

0≤0.351.4

Missense OE?0.57 (0.52–0.61)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 6 / 90.9Missense obs/exp: 468 / 826.2Syn Z: 2.02

This gene — mechanism propensity

0.2997th %ile

GOF

0.3491th %ile

LOF

0.70top 10%

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

LOFprediction above median · LOEUF 0.13

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

208 submitted variants in ClinVar

ClinVar

Classification Summary

VUS162

Likely Benign18

Benign6

162

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	160	0	0	162
Likely Benign	0	6	4	8	18
Benign	0	0	0	6	6
Total	2	166	4	14	186

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap UBR3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →