Menkes disease: genes and variants
Explore variant evidence for Menkes disease across 1 analyzed protein (ATP7A). Linked ClinVar records include 29 pathogenic or likely pathogenic variants, 441 variants of uncertain significance and 123 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Menkes disease
ATP7A: Copper-transporting ATPase 1
It delivers copper to secretory-pathway enzymes and exports excess copper from cells, making it essential for systemic copper distribution. Loss-of-function variants cause Menkes disease or occipital horn syndrome, while some hypomorphic alleles produce distal motor neuropathy.
29 ClinVar pathogenic / likely pathogenic and 564 uncertain variants in ATP7A have source records linked to Menkes disease. Association strength is not clinical gene validity.
Where Menkes disease variants cluster
- ATP7A Cytoplasmic (positions 1012–1356): 14 of 29 ClinVar pathogenic / likely pathogenic variants, 2.1× more than its size predicts.
- ATP7A Transmembrane (positions 1386–1405): 3 of 29 ClinVar pathogenic / likely pathogenic variants, 7.8× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Menkes disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ATP7A T1046I | 1046 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ATP7A N1304S | 1304 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ATP7A A1362V | 1362 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| ATP7A A1284V | 1284 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ATP7A G666R | 666 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| ATP7A G727R | 727 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| ATP7A P1001L | 1001 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| ATP7A G1315R | 1315 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ATP7A K1037N | 1037 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ATP7A D1044E | 1044 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A G1047E | 1047 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A D1305N | 1305 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A P1307R | 1307 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A A1362D | 1362 | Transmembrane | Pathogenic / likely pathogenic (★) |
| ATP7A Q724H | 724 | Transmembrane | Pathogenic / likely pathogenic (★) |
| ATP7A M786R | 786 | Transmembrane | Pathogenic / likely pathogenic (★) |
| ATP7A P852L | 852 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A V917D | 917 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A K927N | 927 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A G1017R | 1017 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A G1019D | 1019 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A G1118C | 1118 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A G1255E | 1255 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A Q1267L | 1267 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| ATP7A G1375R | 1375 | Extracellular | Pathogenic / likely pathogenic (★) |
| ATP7A P1386S | 1386 | Transmembrane | Pathogenic / likely pathogenic (★) |
| ATP7A S1396L | 1396 | Transmembrane | Pathogenic / likely pathogenic (★) |
| ATP7A S1390P | 1390 | Transmembrane | Pathogenic / likely pathogenic (★) |
| ATP7A S637L | 637 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
Which prediction tools work for Menkes disease
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- EVE: 94 out of 100
- AlphaMissense: 94 out of 100
- MetaLR: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MutPred2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 84 out of 100
Same protein, different disease
- X-linked distal spinal muscular atrophy type 3 also has ClinVar records linked to ATP7A variants; they fall mostly in different places as the Menkes disease variants (6 pathogenic / likely pathogenic).
Diseases related to Menkes disease
- Ehlers-Danlos syndrome, also linked to ATP7A
- Cutis laxa, also linked to ATP7A
- X-linked distal spinal muscular atrophy type 3, also linked to ATP7A
Frequently asked questions
Which genes have records linked to Menkes disease?
This view contains 1 analyzed proteins: ATP7A. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 29 pathogenic or likely pathogenic variants, 441 variants of uncertain significance and 123 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 818 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center