RECQL4

Chr 8AR

RecQ like helicase 4

NCBI Gene: 9401ENSG00000160957UniProt: O94761

An ATP-dependent DNA helicase which unwinds dsDNA with a 3'-overhang in a 3'-5' direction (PubMed:28653661). Does not unwind more than 18 bp of dsDNA (PubMed:28653661). May modulate chromosome segregation. The N-terminal domain (residues 1-54) binds DNA Y-shaped DNA better than ss- or dsDNA (PubMed:22730300). The core helicase domain binds ssDNA (PubMed:22730300, PubMed:28653661)

Primary Disease Associations & Inheritance

Baller-Gerold syndromeMIM #218600
AR
RAPADILINO syndromeMIM #266280
AR
Rothmund-Thomson syndrome, type 2MIM #268400
AR
580
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RECQL4
🧬
Gene-Disease Validity (ClinGen)
Rothmund-Thomson syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 366 VUS of 580 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.21LOEUF
pLI 0.000
Z-score 0.25
OE 0.96 (0.77–1.21)
Tolerant

Highly tolerant — LoF variants common in population

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.
-4.22Z-score
OE missense 1.43 (1.36–1.51)
1074 obs / 748.9 exp
Tolerant

Tolerant to missense variation

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.0.96 (0.77–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.43 (1.36–1.51)
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.1.63
0≤1.21.6
LoF obs/exp: 54 / 56.0Missense obs/exp: 1074 / 748.9Syn Z: -8.69

ClinVar Variant Classifications

580 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic6
VUS366
Likely Benign179
Conflicting5
24
Pathogenic
6
Likely Pathogenic
366
VUS
179
Likely Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
13
0
24
Likely Pathogenic
3
0
3
0
6
VUS
3
352
11
0
366
Likely Benign
1
17
16
145
179
Benign
0
0
0
0
0
Conflicting
—5
Total1836943145580

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

View in ClinVar →

Protein Context — Lollipop Plot

RECQL4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RECQL4-related Baller-Gerold syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

RECQL4-related Rothmund-Thomson syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Baller-Gerold syndrome

MIM #218600

Molecular basis of disorder known

Autosomal recessive

RAPADILINO syndrome

MIM #266280

Molecular basis of disorder known

Autosomal recessive

Rothmund-Thomson syndrome, type 2

MIM #268400

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — RECQL4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RECQL4 Inhibits Radiation-Induced Tumor Immune Awakening via Suppressing the cGAS-STING Pathway in Hepatocellular Carcinoma.
Hong W et al.·Adv Sci (Weinh)
2024
The versatile RECQL4.
Kellermayer R·Genet Med
2006Review
Rothmund-Thomson syndrome.
Larizza L et al.·Orphanet J Rare Dis
2010Review
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
Bonache S et al.·J Cancer Res Clin Oncol
2018
Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping.
Larizza L et al.·Cancer Lett
2006Review
Estimation of carrier frequencies utilizing the gnomAD database for ACMG recommended carrier screening and Finnish disease heritage conditions in non-Finnish European, Finnish, and Ashkenazi Jewish populations.
Kandolin M et al.·Am J Med Genet A
2024
Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders.
Lu L et al.·Ageing Res Rev
2017Review
Shared and non-overlapping functions of RECQL4 and BLM helicases in chemotherapeutics-induced glioma cell responses.
Wojnicki K et al.·BMC Cancer
2025Cohort
Cancer risk among RECQL4 heterozygotes.
Martin-Giacalone BA et al.·Cancer Genet
2022
RECQ DNA Helicases and Osteosarcoma.
Lu L et al.·Adv Exp Med Biol
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Unmanipulated bone marrow infusion without conditioning can rescue RECQL4 -/- severe combined immunodeficiency.
Grier AE et al.·J Hum Immun
2026🔓 Open Access
Case Report: Rothmund-Thomson syndrome type 2 in Ecuador: clinical and molecular insights into a recurrent RECQL4 variant.
Armas Samaniego MI et al.·Front Pediatr
2026🔓 Open AccessCase report
Clinical, Radiological and Molecular Genetic Findings in Six New Cases with Rothmund-Thomson Syndrome: Evidence for a Founder RECQL4 Variant.
Genç A et al.·Klin Padiatr
2026Cohort
RECQL4 promotes the malignant progression of lung adenocarcinoma through the YBX1/G3BP1-mediated NF-κB signaling pathway.
Li R et al.·Cell Death Discov
2026🔓 Open Access
Novel mutations in the RECQL4 gene affect its helicase functions, interactions with the BLM helicase and chemotherapeutics-induced cell death.
Kaczmarczyk A et al.·Cell Death Discov
2025🔓 Open Access
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