NME8

Chr 7

NME/NM23 family member 8

Also known as: CILD6, DNAI8, HEL-S-99, NDK8, NM23-H8, SPTRX2, TXNDC3, sptrx-2

NCBI Gene: 51314ENSG00000086288UniProt: Q8N427

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 sperm outer dynein arms, and the protein is implicated in ciliary function. Mutations in this gene are implicated in primary ciliary dyskinesia type 6.[provided by RefSeq, Nov 2009]

Primary Disease Associations & Inheritance

UniProtCiliary dyskinesia, primary, 6
505
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NME8
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 269 VUS of 505 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.34LOEUF
pLI 0.000
Z-score -0.19
OE 1.03 (0.80–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.38Z-score
OE missense 1.06 (0.97–1.16)
320 obs / 301.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.03 (0.80–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.97–1.16)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 41 / 39.7Missense obs/exp: 320 / 301.6Syn Z: -1.43

ClinVar Variant Classifications

505 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic3
VUS269
Likely Benign144
Benign65
Conflicting8
16
Pathogenic
3
Likely Pathogenic
269
VUS
144
Likely Benign
65
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
3
0
3
VUS
15
211
38
5
269
Likely Benign
0
9
61
74
144
Benign
0
6
54
5
65
Conflicting
—8
Total1522617284505

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NME8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — NME8
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nuclear functions of NME proteins.
Puts GS et al.·Lab Invest
2018Review
Genetics of Alzheimer's disease.
Chouraki V et al.·Adv Genet
2014Review
Bioinformatics and experimental approaches identify NME8 as a promoter of the metastasis of renal cell carcinoma by activating the JAK/STAT signaling pathway.
Ma Y et al.·Clin Exp Med
2026
Genetic associations of in vivo pathology influence Alzheimer's disease susceptibility.
Seo J et al.·Alzheimers Res Ther
2020
Identification and validation of hub genes and molecular classifications associated with chronic myeloid leukemia.
Zhong F et al.·Front Immunol
2024
Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.
Angelopoulou E et al.·Int J Mol Sci
2024Review
Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease.
Schott JM et al.·Alzheimers Dement
2016
Centenarian controls increase variant effect sizes by an average twofold in an extreme case-extreme control analysis of Alzheimer's disease.
Tesi N et al.·Eur J Hum Genet
2019
Nme gene family evolutionary history reveals pre-metazoan origins and high conservation between humans and the sea anemone, Nematostella vectensis.
Desvignes T et al.·PLoS One
2010
Identification of candidate cancer predisposing variants by performing whole-exome sequencing on index patients from BRCA1 and BRCA2-negative breast cancer families.
Shahi RB et al.·BMC Cancer
2019Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools