ZRANB2

Chr 1

zinc finger RANBP2-type containing 2

Also known as: ZIS, ZIS1, ZIS2, ZNF265

NCBI Gene: 9406ENSG00000132485UniProt: O95218

ZRANB2 encodes a splice factor that binds single-stranded RNA and is required for alternative splicing of specific transcripts, particularly those containing the consensus sequence 5'-AGGUAA-3'. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.18), but specific diseases associated with ZRANB2 mutations have not yet been established in the clinical literature. Given its essential role in RNA splicing and extreme constraint metrics, pathogenic variants would likely cause developmental abnormalities, though the inheritance pattern and clinical phenotype remain to be characterized.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
22
P/LP submissions
0%
P/LP missense
0.18
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— ZRANB2
⚡
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.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 33 VUS of 74 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 0.999
Z-score 4.56
OE 0.04 (0.01–0.18)
Highly constrained

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

Missense Constraint
1.68Z-score
OE missense 0.65 (0.56–0.76)
122 obs / 186.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.04 (0.01–0.18)
0≤0.351.4
Missense OE0.65 (0.56–0.76)
0≤0.61.4
Synonymous OE1.25
0≤1.21.6
LoF obs/exp: 1 / 26.2Missense obs/exp: 122 / 186.4Syn Z: -1.55
DN
0.3892th %ile
GOF
0.3986th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.18

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

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
VUS33
Likely Benign1
22
Pathogenic
33
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
0
0
0
VUS
0
29
4
0
33
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02927056

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

View in ClinVar →

Protein Context — Lollipop Plot

ZRANB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients