DNAL1

dynein axonemal light chain 1, the group of Dyneins, axonemal outer arm complex subunits

Basic information

Region (hg38): 14:73644874-73703732

Previous symbols: [ "C14orf168" ]

Links

ENSG00000119661 ∙ NCBI:83544 ∙ OMIM:610062 ∙ HGNC:23247 ∙ Uniprot:Q4LDG9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 16 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 16 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 16 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 16 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 16	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary	Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing 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, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	20301301; 21496787

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAL1 gene.

• Primary ciliary dyskinesia 16 (53 variants)
• Primary ciliary dyskinesia (30 variants)
• not provided (24 variants)
• not specified (9 variants)
• Inborn genetic diseases (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAL1 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				10		10
missense			14			14
nonsense	1					1
start loss						0
frameshift	2	1	2			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			1	6	1	8
non coding			23	15	23	61
Total	3	1	42	25	23

Highest pathogenic variant AF is 0.0000200

Variants in DNAL1

This is a list of pathogenic ClinVar variants found in the DNAL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-73644885-C-T			Benign (May 11, 2021)
14-73645026-T-G		not specified	Uncertain significance (Dec 16, 2015)
14-73645050-C-G		Primary ciliary dyskinesia 16	Likely benign (May 04, 2023)
14-73645051-C-A		Primary ciliary dyskinesia 16	Likely benign (Feb 24, 2022)
14-73645059-C-T		Primary ciliary dyskinesia 16	Likely benign (Oct 07, 2022)
14-73654765-A-AATAC			Benign (May 24, 2021)
14-73654828-C-T		Primary ciliary dyskinesia 16	Likely benign (Jul 27, 2022)
14-73654828-CT-C			Benign (May 25, 2021)
14-73654832-T-C		Primary ciliary dyskinesia 16	Conflicting classifications of pathogenicity (Jan 28, 2024)
14-73654837-T-G		Primary ciliary dyskinesia 16	Likely benign (Nov 27, 2023)
14-73654842-T-A			Likely benign (Apr 20, 2018)
14-73654843-A-T		Primary ciliary dyskinesia 16	Likely benign (Oct 06, 2016)
14-73654849-G-A		Primary ciliary dyskinesia 16	Likely benign (Oct 13, 2023)
14-73654859-A-G		Primary ciliary dyskinesia 16	Uncertain significance (Jun 11, 2022)
14-73654864-CAA-C		Primary ciliary dyskinesia	Pathogenic (Dec 11, 2023)
14-73654864-CAAA-C		Primary ciliary dyskinesia	Uncertain significance (Jun 14, 2016)
14-73654877-G-A		Primary ciliary dyskinesia 16	Uncertain significance (Aug 13, 2022)
14-73654878-C-T		Primary ciliary dyskinesia 16	Uncertain significance (Oct 11, 2021)
14-73654893-C-T		Primary ciliary dyskinesia 16	Likely benign (Nov 22, 2022)
14-73654894-A-G		Primary ciliary dyskinesia 16 • DNAL1-related disorder	Benign/Likely benign (Nov 07, 2023)
14-73654898-G-A		Primary ciliary dyskinesia 16	Likely benign (Nov 01, 2022)
14-73655011-T-C			Benign (May 24, 2021)
14-73655058-T-G			Benign (Nov 11, 2018)
14-73658731-G-A			Benign (May 11, 2021)
14-73658838-T-C		Primary ciliary dyskinesia 16 • DNAL1-related disorder	Likely benign (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAL1	protein_coding	protein_coding	ENST00000553645	8	58858

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00888	0.942	124644	0	9	124653	0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	54	84.8	0.637	0.00000375	1234
Missense in Polyphen		12	20.462	0.58646		315
Synonymous	0.720	27	32.2	0.839	0.00000150	334
Loss of Function	1.70	5	11.1	0.449	4.67e-7	168

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000132	0.000129
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000644	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000358	0.0000354
Middle Eastern	0.0000644	0.0000556
South Asian	0.0000332	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency (By similarity). Component of the outer arm dynein (ODA). May be involved in a mechanosensory feedback mechanism controlling ODA activity based on external conformational cues by tethering the outer arm dynein heavy chain (DNAH5) to the microtubule within the axoneme (By similarity). Important for ciliary function in the airways and for the function of the cilia that produce the nodal flow essential for the determination of the left-right asymmetry (PubMed:21496787). {ECO:0000250|UniProtKB:Q9XHH2, ECO:0000303|PubMed:21496787}.
• Pathway: Huntington,s disease - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.699
• rvis_EVS: 0.26
• rvis_percentile_EVS: 69.83

Haploinsufficiency Scores

• pHI: 0.368
• hipred: N
• hipred_score: 0.398
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnal1
• 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); hematopoietic system phenotype; respiratory system phenotype; renal/urinary system phenotype; immune system phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: outer dynein arm assembly
• Cellular component: cytoplasm;microtubule;outer dynein arm
• Molecular function: motor activity;protein binding;alpha-tubulin binding;dynein heavy chain binding