DRC1

dynein regulatory complex subunit 1, the group of Dynein regulatory complex

Basic information

Region (hg38): 2:26401919-26456711

Previous symbols: [ "C2orf39", "CCDC164" ]

Links

ENSG00000157856 ∙ NCBI:92749 ∙ OMIM:615288 ∙ HGNC:24245 ∙ Uniprot:Q96MC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 1 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 21 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 21 (Limited), mode of inheritance: AR
• primary ciliary dyskinesia 21 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 21 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 21	AR	Allergy/Immunology/Infectious; Pulmonary	Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial	Allergy/Immunology/Infectious; Pulmonary	23354437

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DRC1 gene.

• Primary ciliary dyskinesia (305 variants)
• not provided (105 variants)
• Primary ciliary dyskinesia 21 (27 variants)
• Inborn genetic diseases (25 variants)
• not specified (10 variants)
• Spermatogenic failure 80 (1 variants)
• DRC1-related condition (1 variants)
• Kartagener syndrome (1 variants)
• Primary ciliary dyskinesia;Primary ciliary dyskinesia 21 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DRC1 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	65	7	73
missense			141	12	10	163
nonsense	4	1	1			6
start loss						0
frameshift	4	2	2			8
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)		4			1	5
splice region			5	13	2	20
non coding				56	57	113
Total	8	7	149	134	75

Highest pathogenic variant AF is 0.0000394

Variants in DRC1

This is a list of pathogenic ClinVar variants found in the DRC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-26401950-T-C			Likely benign (Oct 02, 2019)
2-26401975-C-T			Benign (Jul 06, 2018)
2-26401994-A-T		Primary ciliary dyskinesia	Uncertain significance (Jun 25, 2023)
2-26401996-C-T		Primary ciliary dyskinesia	Uncertain significance (Sep 02, 2021)
2-26401998-G-T		Primary ciliary dyskinesia	Likely benign (May 12, 2021)
2-26401999-C-T		Inborn genetic diseases	Uncertain significance (Dec 15, 2022)
2-26402003-G-A		Primary ciliary dyskinesia	Uncertain significance (Jun 26, 2022)
2-26402004-G-A		Primary ciliary dyskinesia	Likely benign (Oct 05, 2023)
2-26402015-C-T		Primary ciliary dyskinesia • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 07, 2022)
2-26402025-G-C		Primary ciliary dyskinesia • not specified • Primary ciliary dyskinesia 21	Benign/Likely benign (Jan 25, 2024)
2-26402028-C-A		Primary ciliary dyskinesia	Uncertain significance (Mar 13, 2019)
2-26402035-G-A		Primary ciliary dyskinesia	Uncertain significance (Nov 18, 2023)
2-26402045-C-T		Primary ciliary dyskinesia	Uncertain significance (Jul 19, 2023)
2-26402046-C-T		Primary ciliary dyskinesia	Likely benign (May 06, 2021)
2-26402060-C-A		Primary ciliary dyskinesia	Uncertain significance (Feb 10, 2020)
2-26402063-C-G		Primary ciliary dyskinesia • Inborn genetic diseases	Uncertain significance (Nov 19, 2022)
2-26402066-C-G		Primary ciliary dyskinesia	Uncertain significance (Jul 22, 2019)
2-26402072-A-G		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
2-26402076-C-G		Primary ciliary dyskinesia	Likely benign (Nov 13, 2023)
2-26402076-C-T		Primary ciliary dyskinesia	Likely benign (Aug 09, 2022)
2-26402087-A-G		Primary ciliary dyskinesia	Likely benign (Jan 24, 2023)
2-26402090-A-AGCGCATCCAGGCCCG		Primary ciliary dyskinesia	Uncertain significance (Apr 19, 2019)
2-26402096-T-TC		Primary ciliary dyskinesia • Primary ciliary dyskinesia 21	Pathogenic/Likely pathogenic (Jan 25, 2024)
2-26402104-C-G		Primary ciliary dyskinesia	Uncertain significance (Feb 18, 2020)
2-26402105-G-C		Primary ciliary dyskinesia 21	Uncertain significance (Mar 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DRC1	protein_coding	protein_coding	ENST00000288710	17	54796

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.32e-20	0.100	125537	1	210	125748	0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0468	402	399	1.01	0.0000212	4901
Missense in Polyphen		99	105.1	0.94196		1389
Synonymous	-0.475	165	157	1.05	0.00000850	1305
Loss of Function	1.33	35	44.6	0.785	0.00000214	523

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00131	0.00130
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000165	0.000163
Finnish	0.000925	0.000924
European (Non-Finnish)	0.00110	0.00109
Middle Eastern	0.000165	0.000163
South Asian	0.000689	0.000686
Other	0.000658	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes (By similarity). Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with CCDC65/DRC2 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules (PubMed:23354437). {ECO:0000250|UniProtKB:P0DL09, ECO:0000269|PubMed:23354437}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 21 (CILD21) [MIM:615294]: A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. {ECO:0000269|PubMed:23354437, ECO:0000269|PubMed:25186273}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.9
• rvis_percentile_EVS: 89.31

Haploinsufficiency Scores

• pHI: 0.0833
• hipred: N
• hipred_score: 0.196
• ghis: 0.389

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Drc1
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; immune system 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); respiratory system phenotype

Gene ontology

• Biological process: regulation of cilium movement;determination of left/right symmetry;heart development;cilium-dependent cell motility;axonemal dynein complex assembly
• Cellular component: axonemal dynein complex;axoneme;motile cilium