DKC1

dyskerin pseudouridine synthase 1, the group of MicroRNA protein coding host genes|H/ACA ribonucleoprotein complex|Pseudouridine synthases|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): X:154762741-154777689

Previous symbols: [ "DKC" ]

Links

ENSG00000130826 ∙ NCBI:1736 ∙ OMIM:300126 ∙ HGNC:2890 ∙ Uniprot:O60832 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita, X-linked (Definitive), mode of inheritance: XLR
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• Hoyeraal-Hreidarsson syndrome (Supportive), mode of inheritance: AD
• dyskeratosis congenita, X-linked (Strong), mode of inheritance: XL
• dyskeratosis congenita, X-linked (Definitive), mode of inheritance: XL
• DKC1-related disorder (Definitive), mode of inheritance: XL
• dyskeratosis congenita, X-linked (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, X-linked; Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1	XL	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Oncologic; Pulmonary; Renal	For Dyskeratosis congenita, 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; Lung transplant may be indicated in individuals with advanced lung diease; 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; Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 can involve early-onset hearing loss and renal disease, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Identification and management of renal sequelae may be beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary; Renal	14096348; 5442429; 768476; 7272212; 6601257; 3009302; 3236366; 3201986; 1958493; 1361371; 1390173; 8318369; 7607282; 9590285; 8616066; 9042917; 9886310; 10583221; 10364516; 10700698; 12406104; 18005359; 18627054; 19415736; 19327580; 21415081; 20301779; 32554502

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DKC1 gene.

• Dyskeratosis congenita (256 variants)
• not provided (65 variants)
• Dyskeratosis congenita, X-linked (55 variants)
• not specified (20 variants)
• Inborn genetic diseases;Dyskeratosis congenita (20 variants)
• Inborn genetic diseases (6 variants)
• DKC1-related condition (6 variants)
• Dyskeratosis congenita;Inborn genetic diseases (4 variants)
• Hoyeraal-Hreidarsson syndrome (2 variants)
• Congenital cerebellar hypoplasia (1 variants)
• History of neurodevelopmental disorder (1 variants)
• Inherited Immunodeficiency Diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DKC1 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			2	73	5	80
missense	6	9	82	5	1	103
nonsense		1				1
start loss						0
frameshift						0
inframe indel		1	6	3	2	12
splice donor/acceptor (+/-2bp)			1			1
splice region			6	19		25
non coding			4	71	17	92
Total	6	11	95	152	25

Variants in DKC1

This is a list of pathogenic ClinVar variants found in the DKC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-154762795-A-T		not specified	Uncertain significance (Sep 06, 2018)
X-154762824-C-G		Dyskeratosis congenita, X-linked • not specified • Dyskeratosis congenita • DKC1-related disorder	Conflicting classifications of pathogenicity (Jan 24, 2024)
X-154762892-G-A		not specified	Uncertain significance (Jan 13, 2016)
X-154762896-C-G		not specified	Uncertain significance (Oct 19, 2021)
X-154762907-G-T		not specified	Uncertain significance (Jun 18, 2018)
X-154762947-G-C		not specified	Benign (Jul 23, 2018)
X-154762967-TGGC-T		Dyskeratosis congenita	Pathogenic (Jul 13, 2023)
X-154762970-C-T		Dyskeratosis congenita, X-linked • Dyskeratosis congenita	Conflicting classifications of pathogenicity (Apr 28, 2023)
X-154762977-G-A		Dyskeratosis congenita	Likely benign (Aug 07, 2023)
X-154762986-G-A		not specified	Uncertain significance (Sep 27, 2016)
X-154762988-G-A		DKC1-related disorder	Likely benign (Nov 06, 2023)
X-154762989-C-T		Dyskeratosis congenita	Likely benign (Jun 16, 2023)
X-154762991-G-T		Dyskeratosis congenita	Likely benign (Nov 07, 2023)
X-154762992-C-T		Dyskeratosis congenita	Likely benign (Nov 04, 2022)
X-154762997-TTCCGGGCCGTGCTAAC-T		Dyskeratosis congenita	Likely benign (Jan 12, 2024)
X-154762999-C-G		Dyskeratosis congenita	Likely benign (Sep 22, 2023)
X-154763183-C-T			Benign (Mar 03, 2015)
X-154763200-C-T			Likely benign (Apr 24, 2019)
X-154763383-G-A			Likely benign (Feb 18, 2022)
X-154763573-C-G		Dyskeratosis congenita, X-linked	Pathogenic (Apr 01, 2001)
X-154764881-CTG-C		Dyskeratosis congenita	Likely benign (Sep 23, 2023)
X-154764883-G-A		Dyskeratosis congenita	Likely benign (Aug 16, 2023)
X-154764883-G-T		Dyskeratosis congenita	Likely benign (Apr 04, 2023)
X-154764889-G-A		Dyskeratosis congenita	Likely benign (May 25, 2021)
X-154764890-T-A		Dyskeratosis congenita	Likely benign (May 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DKC1	protein_coding	protein_coding	ENST00000369550	15	14934

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000841	107211	1	0	107212	0.00000466

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.40	68	205	0.332	0.0000161	3358
Missense in Polyphen		4	73.653	0.054309		1219
Synonymous	-0.569	79	72.8	1.08	0.00000570	979
Loss of Function	4.44	1	24.9	0.0402	0.00000215	372

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000803	0.0000627
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000803	0.0000627
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:25219674}.
• 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:10583221, ECO:0000269|PubMed:12437656, ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:24914498}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);rRNA processing;Metabolism of RNA;Telomere Extension By Telomerase;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;rRNA modification in the nucleus and cytosol;rRNA processing in the nucleus and cytosol;Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.49

Haploinsufficiency Scores

• pHI: 0.960
• hipred: Y
• hipred_score: 0.783
• ghis: 0.582

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.702

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dkc1
• Phenotype: embryo phenotype; respiratory system phenotype; normal 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); reproductive system phenotype; hematopoietic system phenotype; neoplasm; immune system phenotype; renal/urinary system 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: dkc1
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: enzyme-directed rRNA pseudouridine synthesis;box H/ACA snoRNA 3'-end processing;rRNA processing;RNA processing;telomere maintenance via telomerase;cell population proliferation;rRNA pseudouridine synthesis;snRNA pseudouridine synthesis;positive regulation of telomere maintenance via telomerase;positive regulation of telomerase activity;scaRNA localization to Cajal body;telomerase RNA stabilization;positive regulation of establishment of protein localization to telomere;positive regulation of protein localization to Cajal body;regulation of telomerase RNA localization to Cajal body;positive regulation of telomerase RNA localization to Cajal body;mRNA pseudouridine synthesis
• Cellular component: fibrillar center;nucleus;nucleoplasm;telomerase holoenzyme complex;nucleolus;cytoplasm;box H/ACA snoRNP complex;box H/ACA scaRNP complex;box H/ACA telomerase RNP complex
• Molecular function: telomerase activity;RNA binding;protein binding;pseudouridine synthase activity;box H/ACA snoRNA binding;telomerase RNA binding