NME8 (NME/NM23 family member 8)

Gene

• Entrez ID: 51314
• Gene name: NME/NM23 family member 8
• Gene symbol: NME8
• Synonyms (NCBI Gene): CILD6, DNAI8, HEL-S-99, NM23-H8, SPTRX2, TXNDC3, sptrx-2
• Chromosome: 7
• Chromosome location: 7p14.1
• Summary: This gene encodes a protein with an N-terminal thioredoxin domain and three C-terminal nucleoside diphosphate kinase (NDK) domains, but the NDK domains are thought to be catalytically inactive. The sea urchin ortholog of this gene encodes a component of s

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918300	T>A,C	Pathogenic	Missense variant, coding sequence variant, stop gained
rs146777129	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT041630	hsa-miR-484	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005634	Component	Nucleus	IDA	11737268
GO:0005737	Component	Cytoplasm	IDA	11737268
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005829	Component	Cytosol	IDA
GO:0005930	Component	Axoneme	IBA
GO:0005930	Component	Axoneme	IEA
GO:0005930	Component	Axoneme	ISS
GO:0006308	Process	DNA catabolic process	IDA	16313181
GO:0007283	Process	Spermatogenesis	IEA
GO:0008017	Function	Microtubule binding	IBA
GO:0008017	Function	Microtubule binding	IDA	17360648
GO:0008296	Function	3'-5'-DNA exonuclease activity	IDA	16313181
GO:0016607	Component	Nuclear speck	IDA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0030317	Process	Flagellated sperm motility	IBA
GO:0030317	Process	Flagellated sperm motility	IEA
GO:0034614	Process	Cellular response to reactive oxygen species	IEA
GO:0036126	Component	Sperm flagellum	IEA
GO:0036157	Component	Outer dynein arm	IMP	17360648
GO:0060271	Process	Cilium assembly	IBA
GO:0060271	Process	Cilium assembly	IMP	17360648
GO:0097225	Component	Sperm midpiece	IDA	11737268
GO:0097228	Component	Sperm principal piece	IBA
GO:0097228	Component	Sperm principal piece	IDA	11737268
GO:0097228	Component	Sperm principal piece	IEA
GO:0097598	Component	Sperm cytoplasmic droplet	IEA

Other IDs

• MIM: 607421
• HGNC: 16473
• e!Ensembl: ENSG00000086288

Protein

• UniProt ID: Q8N427
• Protein name: Thioredoxin domain-containing protein 3 (3'-5' exonuclease NME8) (EC 3.1.-.-) (NM23-H8) (NME/NM23 family member 8) (Spermatid-specific thioredoxin-2) (Sptrx-2)
• Protein function: Probably required during the final stages of sperm tail maturation in the testis and/or epididymis, where extensive disulfide bonding of fibrous sheath (FS) proteins occurs. In vitro, it has neither nucleoside diphosphate kinase (NDPK) activity
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00085	Thioredoxin	11 → 115	Thioredoxin	Domain
  PF00334	NDK	155 → 236	Nucleoside diphosphate kinase	Domain
  PF00334	NDK	316 → 452	Nucleoside diphosphate kinase	Domain
  PF00334	NDK	451 → 586	Nucleoside diphosphate kinase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Testis-specific. Expressed only in primary spermatocytes and round spermatids. {ECO:0000269|PubMed:11737268}.
• Sequence:

  MASKKREVQLQTVINNQSLWDEMLQNKGLTVIDVYQAWCGPCRAMQPLFRKLKNELNEDE
  ILHFAVAEADNIVTLQPFRDKCEPVFLFSVNGKIIEKIQGANAPLVNKKVINLIDEERKI
  AAGEMARPQYPEIPLVDSDSEVSEESPCESVQELYSIAIIKPDAVISKKVLEIKRKITKA
  GFIIEAEHKTVLTEEQVVNFYSRIADQCDFEEFVSFMTSGLSYILVVSQGSKHNPPSEET
  EPQTDTEPNERSEDQPEVEAQVTPGMMKNKQDSLQEYLERQHLAQLCDIEEDAANVAKFM
  DAFFPDFKKMKSMKLEKTLALLRPNLFHERKDDVLRIIKDEDFKILEQRQVVLSEKEAQA
  LCKEYENEDYFNKLIENMTSGPSLALVLLRDNGLQYWKQLLGPRTVEEAIEYFPESLCAQ
  FAMDSLPVNQLYGSDSLETAEREIQHFFPLQSTLGLIKPHATSEQREQILKIVKEAGFDL
  TQVKKMFLTPEQIEKIYPKVTGKDFYKDLLEMLSVGPSMVMILTKWNAVAEWRRLMGPTD
  PEEAKLLSPDSIRAQFGISKLKNIVHGASNAYEAKEVVNRLFEDPEEN

• Sequence length: 588

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 6	—	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
DUPUYTREN CONTRACTURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NME8-related disorder	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary ciliary dyskinesia	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Primary ciliary dyskinesia 6	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar ClinGen, ClinVar, GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Thymoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	25486118, 30258121, 33213512	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	27144521		★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Asthenozoospermia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	25486118	Associate	★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders Inherited	Blood coagulation disorder	Pubtator	17360648	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	30947698	Associate	★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Bronchitis, Chronic	Gastric Cancer	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, 6	Ciliary dyskinesia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 6	Ciliary dyskinesia	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	Pubtator	11737268, 17360648, 18434704	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
Cognition Disorders	Cognition disorder	Pubtator	25486118	Associate	★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	11737268	Associate	★☆☆☆☆ 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
Degenerative polyarthritis	Arthritis	LHGDN	16642435, 17304710		★☆☆☆☆ Found in Text Mining only
Familial lichen amyloidosis	Lichen amyloidosis	BEFREE	26993346		★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	25486118		★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	11737268, 17360648	Associate	★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	LHGDN	17360648		★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	BEFREE	30833143		★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Lung Diseases, Obstructive	Lung Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Mild cognitive disorder	Cognitive disorder	BEFREE	25486118		★☆☆☆☆ Found in Text Mining only
Nasal Polyps	Nasal polyposis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	25486118	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	16642435	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	BEFREE	18471322		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	34252604	Associate	★☆☆☆☆ Found in Text Mining only
Otitis Media with Effusion	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	BEFREE	25672891		★☆☆☆☆ Found in Text Mining only
Primary Ciliary Dyskinesia	Ciliary dyskinesia	BEFREE	18270537, 18434704, 30833143		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Primary ciliary dyskinesia	Ciliary dyskinesia	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Recurrent sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Tract Infections	Respiratory system infectious disease	Pubtator	17360648	Associate	★☆☆☆☆ Found in Text Mining only
Rhinitis	Rhinitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Situs inversus totalis	Situs Inversus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Testicular Diseases	Testicular disease	Pubtator	33603952	Associate	★☆☆☆☆ Found in Text Mining only