DCLRE1B

DNA cross-link repair 1B, the group of DNA cross-link repair family

Basic information

Region (hg38): 1:113904618-113914086

Links

ENSG00000118655 ∙ NCBI:64858 ∙ OMIM:609683 ∙ HGNC:17641 ∙ Uniprot:Q9H816 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita, autosomal recessive 8 (Limited), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 8 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, autosomal recessive 8	AR	Allergy/Immunology/Infectious; Hematologic; Oncologic	Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal; Awareness of infectious risk may allow prompt diagnosis and treatment of infections	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Neurologic; Oncologic	35007328

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DCLRE1B gene.

• Hoyeraal-Hreidarsson syndrome;Autosomal recessive dyskeratosis congenita (51 variants)
• Autosomal recessive dyskeratosis congenita;Hoyeraal-Hreidarsson syndrome (45 variants)
• Inborn genetic diseases (17 variants)
• not provided (13 variants)
• not specified (2 variants)
• Fanconi anemia complementation group C (2 variants)
• Dyskeratosis congenita, autosomal recessive 8 (1 variants)
• Hereditary spastic paraplegia 47 (1 variants)
• DCLRE1B-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCLRE1B 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	1		2	28	2	33
missense	1		62	4	3	70
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding					11	11
Total	2	0	68	32	16

Highest pathogenic variant AF is 0.0000788

Variants in DCLRE1B

This is a list of pathogenic ClinVar variants found in the DCLRE1B region.

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

Position	Type	Phenotype	Significance	ClinVar
1-113904627-T-G		Hereditary spastic paraplegia 47	Uncertain significance (Jun 05, 2022)
1-113904631-G-A		Hereditary spastic paraplegia 47	Likely benign (Oct 17, 2022)
1-113904649-T-C		not specified • Hereditary spastic paraplegia 47 • Inborn genetic diseases	Benign (Jan 10, 2024)
1-113904651-G-T		Hereditary spastic paraplegia 47	Uncertain significance (Feb 28, 2021)
1-113904659-G-A		Inborn genetic diseases	Uncertain significance (Nov 12, 2018)
1-113904662-T-C		Hereditary spastic paraplegia 47	Uncertain significance (Jul 17, 2021)
1-113904664-GCA-G		Hereditary spastic paraplegia 47	Pathogenic (Jan 19, 2023)
1-113904666-A-C		Hereditary spastic paraplegia 47	Uncertain significance (Jan 26, 2022)
1-113904669-G-A		Hereditary spastic paraplegia 47 • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Dec 30, 2022)
1-113904677-T-C		Hereditary spastic paraplegia 47	Uncertain significance (Aug 06, 2023)
1-113904680-A-G		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
1-113904681-G-T		Hereditary spastic paraplegia 47	Uncertain significance (-)
1-113904705-C-T		Hereditary spastic paraplegia 47	Uncertain significance (May 06, 2022)
1-113904714-GCATCT-TGGC		not specified • Inborn genetic diseases • Hereditary spastic paraplegia 47	Uncertain significance (Apr 11, 2023)
1-113904715-C-G		Hereditary spastic paraplegia 47	Uncertain significance (Sep 27, 2022)
1-113904752-C-G		not specified	Likely benign (-)
1-113904783-G-C		not specified	Likely benign (Aug 03, 2016)
1-113904937-C-T		Hereditary spastic paraplegia	Uncertain significance (Oct 02, 2017)
1-113904943-G-A		not specified	Benign (Feb 12, 2016)
1-113904989-T-C			Benign (Oct 31, 2018)
1-113905154-C-G			Benign (Jun 26, 2018)
1-113905292-G-T			Benign (Jul 09, 2018)
1-113905575-A-G			Benign (Jul 05, 2018)
1-113905596-G-A		Hoyeraal-Hreidarsson syndrome;Autosomal recessive dyskeratosis congenita	Uncertain significance (Oct 10, 2018)
1-113905598-C-T		Hoyeraal-Hreidarsson syndrome;Autosomal recessive dyskeratosis congenita	Likely benign (Nov 05, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DCLRE1B	protein_coding	protein_coding	ENST00000369563	4	8946

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.539	0.461	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.548	271	298	0.911	0.0000154	3466
Missense in Polyphen		80	101.15	0.79092		1157
Synonymous	0.443	113	119	0.948	0.00000609	1103
Loss of Function	3.27	4	19.6	0.204	0.00000114	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000453	0.000453
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000221	0.000211
Middle Eastern	0.000381	0.000381
South Asian	0.000197	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)- mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. {ECO:0000269|PubMed:15467758, ECO:0000269|PubMed:15572677, ECO:0000269|PubMed:16730175, ECO:0000269|PubMed:16730176, ECO:0000269|PubMed:18468965, ECO:0000269|PubMed:18469862, ECO:0000269|PubMed:19197158, ECO:0000269|PubMed:19411856, ECO:0000269|PubMed:20655466}.
• Disease: DISEASE: Hoyeraal-Hreidarsson syndrome (HHS) [MIM:305000]: A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency. {ECO:0000269|PubMed:20479256}. Note=The gene represented in this entry may be involved in disease pathogenesis. An aberrant splice variant of DCLRE1B, designated Apollo-Delta, has been found in a patient with Hoyeraal-Hreidarsson syndrome (PubMed:20479256). Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome. {ECO:0000269|PubMed:20479256}.
• Pathway: Fanconi Anemia Pathway;DNA Repair (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.713
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.31

Haploinsufficiency Scores

• pHI: 0.0792
• hipred: Y
• hipred_score: 0.694
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dclre1b
• Phenotype: growth/size/body region 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); embryo phenotype

Gene ontology

• Biological process: telomere maintenance;double-strand break repair via nonhomologous end joining;mitotic cell cycle checkpoint;telomere maintenance via telomere lengthening;telomere capping;telomeric loop formation;protection from non-homologous end joining at telomere;telomeric 3' overhang formation;interstrand cross-link repair;nucleic acid phosphodiester bond hydrolysis
• Cellular component: chromosome, telomeric region;nuclear chromosome, telomeric region;nucleoplasm;cytoplasm;centrosome;nuclear body
• Molecular function: damaged DNA binding;protein binding;5'-3' exonuclease activity;5'-3' exodeoxyribonuclease activity;protein homodimerization activity;protein-containing complex binding