RECQL4

Chr 8AR

RecQ like helicase 4

Also known as: RECQ4

The RECQL4 protein is an ATP-dependent DNA helicase that unwinds double-stranded DNA and may modulate chromosome segregation. Mutations cause autosomal recessive disorders including Rothmund-Thomson syndrome type 2, RAPADILINO syndrome, and Baller-Gerold syndrome, which are rare multisystem conditions affecting growth, skeletal development, and often associated with increased cancer risk. The gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.213 OMIM phenotypes
Clinical SummaryRECQL4
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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.
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ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 231 VUS of 400 total submissions
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GeneReview available — RECQL4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.21LOEUF
pLI 0.000
Z-score 0.25
OE 0.96 (0.771.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-4.22Z-score
OE missense 1.43 (1.361.51)
1074 obs / 748.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.96 (0.771.21)
00.351.4
Missense OE1.43 (1.361.51)
00.61.4
Synonymous OE1.63
01.21.6
LoF obs/exp: 54 / 56.0Missense obs/exp: 1074 / 748.9Syn Z: -8.69

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic7
VUS231
Likely Benign126
Conflicting7
29
Pathogenic
7
Likely Pathogenic
231
VUS
126
Likely Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
0
6
0
29
Likely Pathogenic
5
1
1
0
7
VUS
4
207
18
2
231
Likely Benign
0
9
25
92
126
Benign
0
0
0
0
0
Conflicting
7
Total322175094400

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗