NME5

Chr 5AR

NME/NM23 family member 5

Also known as: CILD48, NDK5, NM23-H5, NM23H5, RSPH23

NCBI Gene: 8382ENSG00000112981UniProt: P56597

Enables 3'-5' exonuclease activity. Involved in spermatid development. Predicted to be located in 9+2 motile cilium. Predicted to be part of radial spoke. Predicted to be active in cilium. Implicated in primary ciliary dyskinesia. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 48, without situs inversusMIM #620032
AR
0
Active trials
15
Pathogenic / LP
50
ClinVar variants
4
Pubs (1 yr)
0.4
Missense Z
1.28
LOEUF
Clinical Summary— NME5
🧬
Gene-Disease Validity (ClinGen)
ciliary dyskinesia, primary, 48, without situs inversus · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 32 VUS of 50 total submissions
📖
GeneReview available — NME5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.001
Z-score 0.98
OE 0.65 (0.36–1.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.41Z-score
OE missense 0.89 (0.76–1.05)
103 obs / 115.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.36–1.28)
0≤0.351.4
Missense OE0.89 (0.76–1.05)
0≤0.61.4
Synonymous OE0.61
0≤1.21.6
LoF obs/exp: 6 / 9.2Missense obs/exp: 103 / 115.5Syn Z: 1.86
DN
DN
0.6261th %ile
GOF
0.5661th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS32
Likely Benign2
Benign1
14
Pathogenic
1
Likely Pathogenic
32
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
13
0
14
Likely Pathogenic
0
0
1
0
1
VUS
1
25
6
0
32
Likely Benign
0
1
1
0
2
Benign
0
0
1
0
1
Total22622050

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

View in ClinVar →

NME5 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients