DNAL4

dynein axonemal light chain 4, the group of Dyneins, axonemal outer arm complex subunits

Basic information

Region (hg38): 22:38778507-38794198

Links

ENSG00000100246 ∙ NCBI:10126 ∙ OMIM:610565 ∙ HGNC:2955 ∙ Uniprot:O96015 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial congenital mirror movements (Supportive), mode of inheritance: AD
• mirror movements 3 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mirror movements 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	25098561

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAL4 gene.

• Inborn genetic diseases (5 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAL4 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	1
missense			5			5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	5	0	1

Variants in DNAL4

This is a list of pathogenic ClinVar variants found in the DNAL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-38779488-G-A		DNAL4-related disorder	Likely benign (Feb 27, 2019)
22-38779492-T-A		not specified	Uncertain significance (Sep 16, 2021)
22-38779601-T-C		not specified	Uncertain significance (Feb 23, 2023)
22-38780924-A-G		Mirror movements 3	Pathogenic (Nov 01, 2014)
22-38780988-T-C		not specified	Uncertain significance (May 31, 2023)
22-38780989-C-G		not specified	Uncertain significance (Jul 07, 2022)
22-38782688-C-T		not specified	Uncertain significance (Sep 16, 2021)
22-38782696-A-G		not specified	Benign (Mar 29, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAL4	protein_coding	protein_coding	ENST00000216068	3	15691

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00283	0.591	125729	0	7	125736	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.446	54	64.0	0.843	0.00000376	691
Missense in Polyphen		8	15.733	0.50848		171
Synonymous	0.844	20	25.4	0.787	0.00000175	182
Loss of Function	0.378	4	4.90	0.816	2.50e-7	57

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity (By similarity). {ECO:0000250}.
• Disease: DISEASE: Mirror movements 3 (MRMV3) [MIM:616059]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. {ECO:0000269|PubMed:25098561}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Huntington,s disease - Homo sapiens (human);Signal Transduction;Retrograde neurotrophin signalling;Signaling by NTRK1 (TRKA);Signaling by NTRKs;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.195
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.269
• hipred: Y
• hipred_score: 0.510
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.401

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnal4
• 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: microtubule-based movement;positive regulation of ATP-dependent microtubule motor activity, plus-end-directed
• Cellular component: cytoplasm;microtubule;plasma membrane;cilium;dynein complex
• Molecular function: microtubule motor activity;protein binding;ATP-dependent microtubule motor activity, plus-end-directed;dynein intermediate chain binding;dynein light intermediate chain binding