DZIP3

Chr 3

DAZ interacting zinc finger protein 3

Also known as: PPP1R66, UURF2, hRUL138

NCBI Gene: 9666 ENSG00000198919 UniProt: Q86Y13 OMIM: 608672

DZIP3 encodes an E3 ubiquitin ligase that mediates ubiquitination and proteasomal degradation of target proteins and can specifically bind RNA. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain malformations. The gene is highly constrained against loss-of-function variants, indicating intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including phosphatase binding activity; polyubiquitin modification-dependent protein binding activity; and ubiquitin-protein transferase activity. Involved in protein polyubiquitination. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— DZIP3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

141 VUS of 191 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.96

OE 0.48 (0.36–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.71Z-score

OE missense 0.92 (0.85–0.98)

549 obs / 598.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.36–0.65)

0≤0.351.4

Missense OE?0.92 (0.85–0.98)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 33 / 68.4Missense obs/exp: 549 / 598.0Syn Z: 0.50

ClinVar Variant Classifications

191 submitted variants in ClinVar

ClinVar

Classification Summary

VUS141

Likely Benign5

Benign2

141

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	141	0	141
Likely Benign	5	0	5
Benign	1	1	2
Total	147	1	148

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap DZIP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →