DCLRE1C

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

Basic information

Region (hg38): 10:14897359-14954432

Previous symbols: [ "SCIDA" ]

Links

ENSG00000152457 ∙ NCBI:64421 ∙ OMIM:605988 ∙ HGNC:17642 ∙ Uniprot:Q96SD1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe combined immunodeficiency due to DCLRE1C deficiency (Definitive), mode of inheritance: AR
• Omenn syndrome (Limited), mode of inheritance: AR
• severe combined immunodeficiency due to DCLRE1C deficiency (Supportive), mode of inheritance: AR
• Omenn syndrome (Supportive), mode of inheritance: AR
• severe combined immunodeficiency due to DCLRE1C deficiency (Strong), mode of inheritance: AR
• severe combined immunodeficiency due to DCLRE1C deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Omenn syndrome; Severe combined immunodeficiency with sensitivity to ionizing radiation	AR	Allergy/Immunology/Infectious	Individuals typically present early in life with sequelae of infections, which are typically frequent and can be severe, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT may be beneficial	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal	12055248; 12569164; 15731174; 19912631; 21184155

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DCLRE1C gene.

• Severe combined immunodeficiency due to DCLRE1C deficiency (57 variants)
• Histiocytic medullary reticulosis (10 variants)
• not provided (4 variants)
• Athabaskan severe combined immunodeficiency (3 variants)
• Severe combined immunodeficiency due to DCLRE1C deficiency;Histiocytic medullary reticulosis (2 variants)
• Severe combined immunodeficiency disease (2 variants)
• Severe combined immunodeficiency, partial (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCLRE1C 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	291	3	295
missense	2	11	242	9	8	272
nonsense	24	16	4			44
start loss			1			1
frameshift	25	30	8			63
inframe indel			3			3
splice donor/acceptor (+/-2bp)	8	26	1			35
splice region		2	14	56		72
non coding			51	127	21	199
Total	59	83	311	427	32

Highest pathogenic variant AF is 0.0000395

Variants in DCLRE1C

This is a list of pathogenic ClinVar variants found in the DCLRE1C region.

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

Position	Type	Phenotype	Significance	ClinVar
10-14897387-C-G		not specified	Uncertain significance (May 21, 2024)
10-14897449-C-T		not specified	Likely benign (Jul 21, 2021)
10-14899056-T-G		not specified	Benign (Jan 24, 2024)
10-14899187-G-A			Likely benign (Oct 01, 2023)
10-14899206-G-C			Likely benign (Nov 01, 2023)
10-14899234-C-T		Severe combined immunodeficiency due to DCLRE1C deficiency • Histiocytic medullary reticulosis • not specified	Benign (Jan 24, 2024)
10-14899244-C-G		SUV39H2-related disorder	Likely benign (Jun 05, 2019)
10-14899283-G-A		DCLRE1C-related disorder	Likely benign (Jun 20, 2019)
10-14899533-G-C			Benign (Mar 29, 2018)
10-14899588-A-G		not specified	Uncertain significance (Sep 12, 2023)
10-14902418-T-C		not specified	Uncertain significance (May 24, 2024)
10-14902438-C-G		not specified	Uncertain significance (Oct 05, 2023)
10-14906873-T-C		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14906883-T-A		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14906921-C-G		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14906956-C-T		Histiocytic medullary reticulosis	Uncertain significance (Jan 12, 2018)
10-14907000-C-T		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14907001-G-A		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14907014-G-A		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14907018-A-C		Histiocytic medullary reticulosis	Uncertain significance (Jun 14, 2016)
10-14907018-A-G		Histiocytic medullary reticulosis	Benign (Jan 13, 2018)
10-14907069-C-G		Histiocytic medullary reticulosis	Benign (Jan 13, 2018)
10-14907121-A-G		Histiocytic medullary reticulosis	Benign (Jan 13, 2018)
10-14907128-G-A		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)
10-14907132-G-C		Histiocytic medullary reticulosis	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DCLRE1C	protein_coding	protein_coding	ENST00000378278	14	57074

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.49e-7	0.999	125583	0	165	125748	0.000656

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.678	391	355	1.10	0.0000180	4540
Missense in Polyphen		99	114.48	0.86475		1463
Synonymous	-2.14	161	130	1.24	0.00000688	1285
Loss of Function	2.92	17	35.9	0.474	0.00000192	455

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000781	0.000778
Ashkenazi Jewish	0.00248	0.00248
East Asian	0.000489	0.000489
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000502	0.000501
Middle Eastern	0.000489	0.000489
South Asian	0.00124	0.00124
Other	0.00245	0.00245

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ. {ECO:0000269|PubMed:11336668, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12055248, ECO:0000269|PubMed:14744996, ECO:0000269|PubMed:15071507, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15468306, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:15574327, ECO:0000269|PubMed:15811628, ECO:0000269|PubMed:15936993}.
• Disease: DISEASE: Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]: A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T- cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity. {ECO:0000269|PubMed:11336668, ECO:0000269|PubMed:12406895, ECO:0000269|PubMed:12569164, ECO:0000269|PubMed:12592555, ECO:0000269|PubMed:12921762}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:602450]: A variety of SCID with sensitivity to ionizing radiation. A founder mutation has been detected in Athabascan- speaking native Americans, being inherited as an autosomal recessive trait. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID. {ECO:0000269|PubMed:12055248}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. {ECO:0000269|PubMed:15731174}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary immunodeficiency - Homo sapiens (human);Non-homologous end-joining - Homo sapiens (human);ATM Signaling Network in Development and Disease;DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;ATM pathway;DNA-PK pathway in nonhomologous end joining (Consensus)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.908
• rvis_EVS: 0.07
• rvis_percentile_EVS: 59.04

Haploinsufficiency Scores

• pHI: 0.218
• hipred: Y
• hipred_score: 0.718
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.893

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dclre1c
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: adaptive immune response;double-strand break repair via nonhomologous end joining;response to ionizing radiation;B cell differentiation;protection from non-homologous end joining at telomere;V(D)J recombination;interstrand cross-link repair;nucleic acid phosphodiester bond hydrolysis
• Cellular component: nuclear chromosome, telomeric region;nucleoplasm;Golgi apparatus;nonhomologous end joining complex
• Molecular function: single-stranded DNA endodeoxyribonuclease activity;damaged DNA binding;endonuclease activity;protein binding;5'-3' exonuclease activity;5'-3' exodeoxyribonuclease activity