DNAAF4 (dynein axonemal assembly factor 4)

Gene

• Entrez ID: 161582
• Gene name: Dynein axonemal assembly factor 4
• Gene symbol: DNAAF4
• Synonyms (NCBI Gene): CILD25, DYX1, DYX1C1, DYXC1, EKN1, RD, pf23
• Chromosome: 15
• Chromosome location: 15q21.3
• Summary: This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in th

Transcription factors

Transcription factor	Regulation	Reference
GTF2I	Unknown	18445785
PARP1	Unknown	18445785
SFPQ	Unknown	18445785

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001764	Process	Neuron migration	ISS
GO:0003341	Process	Cilium movement	IEA
GO:0003341	Process	Cilium movement	IMP	23872636
GO:0003351	Process	Epithelial cilium movement involved in extracellular fluid movement	IBA
GO:0003351	Process	Epithelial cilium movement involved in extracellular fluid movement	IEA
GO:0005515	Function	Protein binding	IPI	19423554, 20562859, 23872636, 25416956, 26871637, 28041644, 29601588, 32296183
GO:0005576	Component	Extracellular region	IEA
GO:0005634	Component	Nucleus	IDA	16989952, 19423554
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	16989952, 19423554, 23872636
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IDA
GO:0007368	Process	Determination of left/right symmetry	IBA
GO:0007368	Process	Determination of left/right symmetry	IEA
GO:0007368	Process	Determination of left/right symmetry	IMP	23872636
GO:0007399	Process	Nervous system development	IEA
GO:0007507	Process	Heart development	IBA
GO:0007507	Process	Heart development	IEA
GO:0007611	Process	Learning or memory	IEA
GO:0030331	Function	Nuclear estrogen receptor binding	IBA
GO:0030331	Function	Nuclear estrogen receptor binding	IDA	19423554
GO:0033146	Process	Regulation of intracellular estrogen receptor signaling pathway	IDA	19423554
GO:0036158	Process	Outer dynein arm assembly	IBA
GO:0036158	Process	Outer dynein arm assembly	IEA
GO:0036158	Process	Outer dynein arm assembly	IMP	23872636
GO:0036159	Process	Inner dynein arm assembly	IBA
GO:0036159	Process	Inner dynein arm assembly	IEA
GO:0036159	Process	Inner dynein arm assembly	IMP	23872636
GO:0042995	Component	Cell projection	IEA
GO:0043005	Component	Neuron projection	IEA
GO:0051649	Process	Establishment of localization in cell	IEA
GO:0061136	Process	Regulation of proteasomal protein catabolic process	IDA	19423554
GO:0120293	Component	Dynein axonemal particle	IEA
GO:0120293	Component	Dynein axonemal particle	ISS

Other IDs

• MIM: 608706
• HGNC: 21493
• e!Ensembl: ENSG00000256061

Protein

• UniProt ID: Q8WXU2
• Protein name: Dynein axonemal assembly factor 4 (Dyslexia susceptibility 1 candidate gene 1 protein)
• Protein function: Axonemal dynein assembly factor required for ciliary motility. Involved in neuronal migration during development of the cerebral neocortex. May regulate the stability and proteasomal degradation of the estrogen receptors that play an important r
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04969	CS	6 → 77	CS domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in several tissues, including brain, lung, kidney and testis. In brain localizes to a fraction of cortical neurons and white matter glial cells. {ECO:0000269|PubMed:12954984}.
• Sequence:

  MPLQVSDYSWQQTKTAVFLSLPLKGVCVRDTDVFCTENYLKVNFPPFLFEAFLYAPIDDE
  SSKAKIGNDTIVFTLYKKEAAMWETLSVTGVDKEMMQRIREKSILQAQERAKEATEAKAA
  AKREDQKYALSVMMKIEEEERKKIEDMKENERIKATKALEAWKEYQRKAEEQKKIQREEK
  LCQKEKQIKEERKKIKYKSLTRNLASRNLAPKGRNSENIFTEKLKEDSIPAPRSVGSIKI
  NFTPRVFPTALRESQVAEEEEWLHKQAEARRAMNTDIAELCDLKEEEKNPEWLKDKGNKL
  FATENYLAAINAYNLAIRLNNKMPLLYLNRAACHLKLKNLHKAIEDSSKALELLMPPVTD
  NANARMKAHVRRGTAFCQLELYVEGLQDYEAALKIDPSNKIVQIDAEKIRNVIQGTELKS
  

• Sequence length: 420

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
DNAAF4-related disorder	Likely pathogenic; Pathogenic	rs762704959, rs779538333, rs751610886	RCV003426065 RCV004751412 RCV003403380	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Dyslexia, susceptibility to, 1	Pathogenic; Likely pathogenic	rs982697369, rs2058668062, rs751610886, rs753649614, rs397515621, rs774796257	RCV004820893 RCV003990385 RCV002476354 RCV003989587 RCV002504978 RCV005860186	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary ciliary dyskinesia	Likely pathogenic; Pathogenic	rs781156334, rs751610886, rs770136467, rs201173498	RCV005626799 RCV000610966 RCV001268924 RCV001255276	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary ciliary dyskinesia 25	Pathogenic; Likely pathogenic	rs2543406965, rs781156334, rs751610886, rs1302509857, rs753649614, rs397515621, rs397515622, rs2058179740, rs201173498	RCV003225692 RCV003320449 RCV003129933 RCV002476354 RCV005632535 RCV001507021 RCV000059318 RCV000059319 RCV001078457 RCV003142192	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Respiratory ciliopathies including non-CF bronchiectasis	Likely pathogenic; Pathogenic	rs397515621	RCV006261947	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CILIARY DYSKINESIA, PRIMARY, 1, WITH OR WITHOUT SITUS INVERSUS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 25	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY MOTILITY DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ATRESIA OF NASOPHARYNX	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSLEXIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFERTILITY, MALE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MALE INFERTILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYNESIAN BRONCHIECTASIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alexia	Alexia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Asthenozoospermia	Pubtator	37147940	Associate	★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Asthenozoospermia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	19076634, 30379906		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	15470369		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	19277710, 22375924		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	19277710, 22375924	Associate	★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bronchitis, Chronic	Gastric Cancer	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	23872636		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliary Dyskinesia, Primary, 1, With Or Without Situs Inversus	Ciliary Dyskinesia	ORPHANET_DG	23872636		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Dyskinesia, Primary, 1, With Or Without Situs Inversus	Ciliary Dyskinesia	CTD_human_DG	23872636		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 25	Ciliary Dyskinesia	GENOMICS_ENGLAND_DG	23872636		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 25	Ciliary Dyskinesia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 25	Ciliary Dyskinesia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	Pubtator	24824133, 25186273, 26123568, 28801648, 37147940	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliopathies	Ciliopathies	BEFREE	27451412		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	18618141		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of spleen	Asplenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Corneal dystrophy	Corneal Dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental reading disorder	Developmental dyslexia	BEFREE	12954984, 15470369, 15702132, 16280601, 17309662, 19277710, 19423554, 21046216, 21203818, 22326444, 22383464, 24362368		★☆☆☆☆ Found in Text Mining only
Developmental reading disorder	Developmental dyslexia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Dyslexia	Dyslexia	BEFREE	10507721, 11015455, 12954984, 15007729, 15249932, 15389770, 16133186, 16280601, 16781891, 17309879, 17450541, 18445785, 18521840, 19240663, 19277710, 19423554, 19901951, 20798984, 21599957, 22326444, 22375924, 22383464, 22426781, 22683091, 23028439, 23065966, 23872636, 25989970, 26400686, 27451412, 27510895, 28074887, 30379906		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyslexia	Dyslexia	LHGDN	12954984, 15249932, 15477871, 17450541		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyslexia	Dyslexia	Pubtator	12954984, 17309662, 18445785, 19277710, 20846247, 21046216, 21599957, 22375924, 22383464, 23028439, 23176554, 24022301, 25339756, 26400686, 28074887, 29201552, 30379906, 32445086, 33960276	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyslexia	Dyslexia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyslexia	Dyslexia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hydrocephalus	Hydrocephalus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	CTD_human_DG	23872636		★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	ORPHANET_DG	23872636		★☆☆☆☆ Found in Text Mining only
Lung Diseases, Obstructive	Lung Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	19277710, 22375924		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	18618141, 19277710, 22375924		★☆☆☆☆ Found in Text Mining only
Nasal Polyps	Nasal polyposis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22375924		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	22558177		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	22383464		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	22383464	Associate	★☆☆☆☆ Found in Text Mining only
Neuronal heterotopia	Neuronal Heterotopia	BEFREE	17259020		★☆☆☆☆ Found in Text Mining only
Otitis Media with Effusion	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polynesian Bronchiectasis	Kartagener syndrome	CTD_human_DG	23872636		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polynesian Bronchiectasis	Kartagener syndrome	ORPHANET_DG	23872636		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary Ciliary Dyskinesia	Ciliary dyskinesia	BEFREE	23872636, 24824133		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary Ciliary Dyskinesia	Ciliary dyskinesia	ORPHANET_DG	23872636		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary ciliary dyskinesia	Ciliary dyskinesia	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Recurrent sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rhinitis	Rhinitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Situs inversus totalis	Situs Inversus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Speech Disorders	Speech Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only