RECQL4

RecQ like helicase 4, the group of RecQ like helicases

Basic information

Region (hg38): 8:144511288-144517845

Links

ENSG00000160957 ∙ NCBI:9401 ∙ OMIM:603780 ∙ HGNC:9949 ∙ Uniprot:O94761 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Rothmund-Thomson syndrome (Definitive), mode of inheritance: AR
• congenital heart disease (No Known Disease Relationship), mode of inheritance: AD
• rapadilino syndrome (Strong), mode of inheritance: AR
• Rothmund-Thomson syndrome type 2 (Strong), mode of inheritance: AR
• osteosarcoma (Strong), mode of inheritance: AR
• Rothmund-Thomson syndrome type 2 (Strong), mode of inheritance: AR
• Baller-Gerold syndrome (Supportive), mode of inheritance: AR
• rapadilino syndrome (Supportive), mode of inheritance: AR
• Rothmund-Thomson syndrome type 2 (Supportive), mode of inheritance: AR
• Baller-Gerold syndrome (Definitive), mode of inheritance: AR
• Rothmund-Thomson syndrome type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Baller-Gerold syndrome; RAPADILINO syndrome; Rothmund-Thomson syndrome 2	AR	Oncologic	While the disorders may be recognizable, individuals may be at risk for neoplasms, and awareness may allow early diagnosis and treatment, which may reduce morbidity and mortality	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Oncologic; Renal	8160763; 10678659; 12838562; 12952869; 15964893; 18716613; 20113479; 20503338; 27247962; 27287744; 27859906; 28039508; 28358413; 28486640; 29224249; 29367366; 29462647; 29642415; 29659569; 30007837; 31406625; 31428572; 32482547; 35025765

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RECQL4 gene.

• Baller-Gerold_syndrome (4795 variants)
• Inborn_genetic_diseases (1769 variants)
• not_provided (450 variants)
• Rothmund-Thomson_syndrome_type_2 (225 variants)
• Hereditary_cancer-predisposing_syndrome (184 variants)
• RECQL4-related_disorder (159 variants)
• Rapadilino_syndrome (158 variants)
• not_specified (123 variants)
• Rothmund-Thomson_syndrome (46 variants)
• Ovarian_cancer (26 variants)
• Familial_meningioma (3 variants)
• Congenital_heart_disease (2 variants)
• RECQL4-related_spectrum_disorders (2 variants)
• Ehlers-Danlos_syndrome (2 variants)
• Malignant_tumor_of_breast (2 variants)
• High_grade_surface_osteosarcoma (1 variants)
• See_cases (1 variants)
• Multiple_myeloma (1 variants)
• Malignant_fibrous_histiocytoma (1 variants)
• B_lymphoblastic_leukemia_lymphoma_with_t(12%3B21)(p13%3Bq22)%3B_TEL-AML1_(ETV6-RUNX1) (1 variants)
• Absent_radius (1 variants)
• Susceptibility_to_severe_COVID-19 (1 variants)
• Hepatoblastoma (1 variants)
• Familial_cancer_of_breast (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RECQL4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004260.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			43	1209	5	1257
missense	6	16	2632	148	14	2816
nonsense	102	12	9			123
start loss			6			6
frameshift	170	28	12		1	211
splice donor/acceptor (+/-2bp)	11	61	29	1		102
Total	289	117	2731	1358	20

Highest pathogenic variant AF is 0.00040140163

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RECQL4	protein_coding	protein_coding	ENST00000428558	22	6563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		4672	119559	53	124284	0.806

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-4.22	1074	749	1.43	0.0000492	7582
Missense in Polyphen		253	195.55	1.2938		2016
Synonymous	-8.69	502	308	1.63	0.0000193	2568
Loss of Function	0.245	54	56.0	0.965	0.00000273	592

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.00	1.77
Ashkenazi Jewish	1.00	0.866
East Asian	1.00	0.904
Finnish	1.00	0.570
European (Non-Finnish)	1.00	0.818
Middle Eastern	1.00	0.904
South Asian	1.00	0.939
Other	1.00	0.848

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-dependent ATPase. May modulate chromosome segregation. {ECO:0000269|PubMed:15317757}.
• Disease: DISEASE: Rothmund-Thomson syndrome (RTS) [MIM:268400]: Characterized by dermatological features such as atrophy, pigmentation, and telangiectasia and frequently accompanied by juvenile cataract, saddle nose, congenital bone defects, disturbances of hair growth, and hypogonadism. {ECO:0000269|PubMed:10552928}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: RAPADILINO syndrome (RAPADILINOS) [MIM:266280]: Disease characterized by radial and patellar aplasia or hypoplasia. {ECO:0000269|PubMed:12952869}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Baller-Gerold syndrome (BGS) [MIM:218600]: An autosomal recessive syndrome characterized by short stature, craniosynostosis, absent or hypoplastic radii, short and curved ulna, fused carpal bones and absent carpals, metacarpals and phalanges. Some patients manifest poikiloderma. Cases reported as Baller-Gerold syndrome have phenotypic overlap with several other disorders, including Saethre-Chotzen syndrome. {ECO:0000269|PubMed:15964893}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.172

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

• Biological process: telomere maintenance;double-strand break repair via homologous recombination;DNA strand renaturation;DNA replication;DNA repair;base-excision repair;DNA recombination;multicellular organism development;positive regulation of cell population proliferation;positive regulation of G2/M transition of mitotic cell cycle;DNA duplex unwinding;positive regulation of DNA replication;telomeric D-loop disassembly
• Cellular component: chromosome, telomeric region;nucleus;chromosome;cytoplasm;membrane
• Molecular function: bubble DNA binding;DNA binding;single-stranded DNA binding;helicase activity;protein binding;ATP binding;four-way junction helicase activity;oxidized purine DNA binding;annealing helicase activity;ATP-dependent 3'-5' DNA helicase activity;telomeric D-loop binding