ZRSR2

Chr XXLR

zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2

Also known as: OFD21, U2AF1-RS2, U2AF1L2, U2AF1RS2, URP, ZC3H22

NCBI Gene: 8233ENSG00000169249UniProt: Q15696OMIM: 300028

This gene encodes a pre-mRNA-binding protein required for splicing of both U2- and U12-type introns, specifically promoting recognition of 3'-splice sites and assembly of spliceosomal complexes. Mutations cause orofaciodigital syndrome XXI with X-linked recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI >0.99), indicating intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.131 OMIM phenotype
Clinical Summary— ZRSR2
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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
74 unique Pathogenic / Likely Pathogenic· 42 VUS of 129 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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
0.13LOEUF
pLI 1.000
Z-score 4.41
OE 0.00 (0.00–0.13)
Highly constrained

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

Missense Constraint
1.46Z-score
OE missense 0.71 (0.61–0.81)
137 obs / 194.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.13)
0≤0.351.4
Missense OE0.71 (0.61–0.81)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 0 / 22.7Missense obs/exp: 137 / 194.1Syn Z: 0.28
DN
0.4388th %ile
GOF
0.6247th %ile
LOF
0.68top 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

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic3
VUS42
Likely Benign8
Benign1
71
Pathogenic
3
Likely Pathogenic
42
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
69
0
71
Likely Pathogenic
3
0
0
0
3
VUS
0
24
18
0
42
Likely Benign
0
3
0
5
8
Benign
0
0
0
1
1
Total527876125

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

View in ClinVar →

Protein Context — Lollipop Plot

ZRSR2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
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 5 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