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

• Baller-Gerold syndrome (Definitive), mode of inheritance: AR
• Baller-Gerold syndrome (Strong), mode of inheritance: AR
• 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
• Rothmund-Thomson syndrome type 2 (Definitive), mode of inheritance: AR
• Rothmund-Thomson syndrome (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 (256 variants)
• not provided (16 variants)
• Rothmund-Thomson syndrome type 2 (7 variants)
• Rapadilino syndrome (6 variants)
• Rothmund-Thomson syndrome (4 variants)
• Inborn genetic diseases (3 variants)
• RECQL4-related disorder (3 variants)
• Hereditary cancer-predisposing syndrome (2 variants)
• Rothmund-Thomson syndrome type 2;Rapadilino syndrome;Baller-Gerold syndrome (2 variants)
• Rapadilino syndrome;Baller-Gerold syndrome;Rothmund-Thomson syndrome (1 variants)
• B lymphoblastic leukemia lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) (1 variants)
• Rapadilino syndrome;Baller-Gerold syndrome;Rothmund-Thomson syndrome type 2 (1 variants)
• RECQL4-related spectrum disorders (1 variants)
• High grade surface osteosarcoma (1 variants)
• Baller-Gerold syndrome;Rapadilino syndrome;Rothmund-Thomson syndrome type 2 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			74	930	8	1012
missense	1	5	2206	30	16	2258
nonsense	89	8	8			105
start loss			9			9
frameshift	159	15	3		1	178
inframe indel	1	1	72	1	1	76
splice donor/acceptor (+/-2bp)	9	56	14	1		80
splice region			120	134	9	263
non coding	1	3	155	445	21	625
Total	260	88	2541	1407	47

Highest pathogenic variant AF is 0.000394

Variants in RECQL4

This is a list of pathogenic ClinVar variants found in the RECQL4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-144511422-G-C		RECQL4-related disorder	Likely benign (Feb 17, 2022)
8-144511434-G-A		Baller-Gerold syndrome • Hereditary cancer-predisposing syndrome	Likely benign (Jan 19, 2024)
8-144511434-G-C		Baller-Gerold syndrome	Likely benign (Jan 23, 2023)
8-144511434-G-T		Baller-Gerold syndrome • not specified • RECQL4-related disorder	Conflicting classifications of pathogenicity (Jan 11, 2024)
8-144511435-C-T		Baller-Gerold syndrome	Uncertain significance (Oct 11, 2023)
8-144511436-G-A		Baller-Gerold syndrome • Hereditary cancer-predisposing syndrome • Rothmund-Thomson syndrome type 2 • RECQL4-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2024)
8-144511436-G-C		Baller-Gerold syndrome	Uncertain significance (Oct 13, 2023)
8-144511437-G-A		Baller-Gerold syndrome	Likely benign (Oct 23, 2023)
8-144511440-C-T		Baller-Gerold syndrome	Uncertain significance (Oct 21, 2022)
8-144511442-C-G		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
8-144511442-C-T		Baller-Gerold syndrome	Uncertain significance (Jul 25, 2022)
8-144511443-C-G		Baller-Gerold syndrome	Uncertain significance (Aug 23, 2021)
8-144511443-C-T		Baller-Gerold syndrome	Likely benign (May 18, 2022)
8-144511445-G-A		Baller-Gerold syndrome	Uncertain significance (Oct 02, 2021)
8-144511446-CAGG-C		Baller-Gerold syndrome	Uncertain significance (Mar 07, 2017)
8-144511447-A-T		Baller-Gerold syndrome	Uncertain significance (Jun 16, 2021)
8-144511448-G-A		Baller-Gerold syndrome	Uncertain significance (Aug 30, 2022)
8-144511449-G-A		not specified • Baller-Gerold syndrome • Hereditary cancer-predisposing syndrome	Benign/Likely benign (Nov 01, 2024)
8-144511449-G-T		Baller-Gerold syndrome	Likely benign (Dec 30, 2019)
8-144511451-G-A		Baller-Gerold syndrome	Uncertain significance (Dec 26, 2022)
8-144511452-C-A		Baller-Gerold syndrome	Uncertain significance (Jan 12, 2022)
8-144511452-C-G		Baller-Gerold syndrome	Uncertain significance (Oct 29, 2018)
8-144511452-C-T		Baller-Gerold syndrome	Likely benign (May 27, 2023)
8-144511454-C-T		Baller-Gerold syndrome	Uncertain significance (Oct 17, 2022)
8-144511456-T-C		Baller-Gerold syndrome	Uncertain significance (Dec 26, 2023)

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
3.31e-35	0.0000226	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

Haploinsufficiency Scores

• pHI: 0.0665

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

Mouse Genome Informatics

• Gene name: Recql4
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; skeleton phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; pigmentation phenotype; neoplasm; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; limbs/digits/tail phenotype

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