LUC7L2

Chr 7

LUC7 like 2, pre-mRNA splicing factor

Also known as: CGI-59, CGI-74, LUC7B2

NCBI Gene: 51631ENSG00000146963UniProt: Q9Y383

This gene encodes a protein that contains a C2H2-type zinc finger, coiled-coil region and arginine, serine-rich (RS) domain. A similar protein in mouse interacts with sodium channel modifier 1, and the encoded protein may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

81
ClinVar variants
45
Pathogenic / LP
0.06
pLI score
0
Active trials
Clinical Summary— LUC7L2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 36 VUS of 81 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.055
Z-score 3.32
OE 0.28 (0.16–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.62Z-score
OE missense 0.51 (0.44–0.60)
117 obs / 228.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.16–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.44–0.60)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.82
0≤1.21.6
LoF obs/exp: 7 / 24.8Missense obs/exp: 117 / 228.7Syn Z: 1.21

ClinVar Variant Classifications

81 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic3
VUS36
42
Pathogenic
3
Likely Pathogenic
36
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
1
2
0
3
VUS
1
28
7
0
36
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total12951081

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

View in ClinVar →

Protein Context — Lollipop Plot

LUC7L2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention.
Yue Q et al.·Adv Sci (Weinh)
2024
The significance of CUX1 and chromosome 7 in myeloid malignancies.
Jotte MRM et al.·Curr Opin Hematol
2022Review
Hydrochlorothiazide-induced hyperuricaemia in the pharmacogenomic evaluation of antihypertensive responses study.
Vandell AG et al.·J Intern Med
2014
Evidence for a direct role of the disease modifier SCNM1 in splicing.
Howell VM et al.·Hum Mol Genet
2007
[Genetic defects of chromosome 5q and 7q in myeloid neoplasms].
Hosono N·Rinsho Ketsueki
2019
Systemic characterization of alternative splicing related to prognosis and immune infiltration in malignant mesothelioma.
Lai J et al.·BMC Cancer
2021
Concurrent detection of targeted copy number variants and mutations using a myeloid malignancy next generation sequencing panel allows comprehensive genetic analysis using a single testing strategy.
Shen W et al.·Br J Haematol
2016Clinical trial
Genomic Insights into Blood Pressure Regulation: Exploring Ion Channel and Transporter Gene Variations in Jordanian Hypertensive Individuals.
Alghamdi MA et al.·Medicina (Kaunas)
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools