RECQL

Chr 12AR

RecQ like helicase

Also known as: RECON, RECQL1, RecQ1

NCBI Gene: 5965 ENSG00000004700 UniProt: P46063 OMIM: 600537

RECQL encodes a DNA helicase that unwinds DNA and resolves DNA structural intermediates during replication and repair, playing a critical role in maintaining genome stability. Biallelic mutations cause RECON progeroid syndrome, an autosomal recessive disorder characterized by premature aging features. The gene shows very low constraint against loss-of-function variants (LOEUF 1.31), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.311 OMIM phenotype

Clinical Summary— RECQL

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Gene-Disease Validity (ClinGen)

hereditary breast carcinoma · ADDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.000

Z-score 0.16

OE 0.97 (0.73–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.96 (0.88–1.05)

322 obs / 334.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.97 (0.73–1.31)

0≤0.351.4

Missense OE?0.96 (0.88–1.05)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 31 / 32.0Missense obs/exp: 322 / 334.8Syn Z: -0.38

This gene — mechanism propensity

0.6261th %ile

GOF

0.3789th %ile

LOF

0.4627th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.