NME8

NME/NM23 family member 8, the group of Dyneins, axonemal outer arm complex subunits|Thioredoxin domain containing |NME/NM23 family

Basic information

Region (hg38): 7:37848597-37900397

Previous symbols: [ "TXNDC3" ]

Links

ENSG00000086288 ∙ NCBI:51314 ∙ OMIM:607421 ∙ HGNC:16473 ∙ Uniprot:Q8N427 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 6 (Limited), mode of inheritance: AR
• primary ciliary dyskinesia 6 (Limited), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 6 (Limited), mode of inheritance: AR
• primary ciliary dyskinesia 6 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 6	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; The condition can involve congenital cardiac anomalies, and awareness may allow early management	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	17360648; 20301301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NME8 gene.

• Primary_ciliary_dyskinesia_6 (293 variants)
• Primary_ciliary_dyskinesia (138 variants)
• not_specified (24 variants)
• not_provided (19 variants)
• NME8-related_disorder (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NME8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016616.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	69		74
missense			190	14	3	207
nonsense			15	3		18
start loss						0
frameshift			8			8
splice donor/acceptor (+/-2bp)			7			7
Total	0	0	225	86	3

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NME8	protein_coding	protein_coding	ENST00000199447	15	51805

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.58e-28	0.0000814	125548	0	198	125746	0.000788

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.376	320	302	1.06	0.0000148	3909
Missense in Polyphen		107	106.84	1.0015		1430
Synonymous	-1.43	127	108	1.18	0.00000611	1011
Loss of Function	-0.188	41	39.7	1.03	0.00000246	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00549	0.00549
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000653	0.000653
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000459	0.000457
Middle Eastern	0.000653	0.000653
South Asian	0.000653	0.000588
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: 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. May be involved in the reduction of disulfide bonds within the sperm FS components. In vitro, it has neither NDP kinase nor reducing activity on disulfide bonds.
• Disease: DISEASE: Ciliary dyskinesia, primary, 6 (CILD6) [MIM:610852]: 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; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients 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:17360648}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.8

Haploinsufficiency Scores

• pHI: 0.0472
• hipred: N
• hipred_score: 0.123
• ghis: 0.436

Essentials

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

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nme8
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; reproductive system phenotype

Gene ontology

• Biological process: multicellular organism development;spermatogenesis;cell differentiation;flagellated sperm motility;cellular response to reactive oxygen species;cell redox homeostasis;cilium assembly
• Cellular component: outer dynein arm;sperm principal piece;sperm cytoplasmic droplet
• Molecular function: microtubule binding