Diabetes mellitus, permanent neonatal 3: genes and variants
Explore variant evidence for Diabetes mellitus, permanent neonatal 3 across 3 analyzed proteins (ABCC8, INS, KCNJ11). Linked ClinVar records include 35 pathogenic or likely pathogenic variants, 32 variants of uncertain significance and 22 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 Diabetes mellitus, permanent neonatal 3
ABCC8: ATP-binding cassette sub-family C member 8
It senses cellular nucleotide levels as the regulatory component of pancreatic beta-cell ATP-sensitive potassium channels and thereby couples glucose metabolism to insulin secretion. Loss-of-function variants cause congenital hyperinsulinism, whereas activating variants can cause neonatal diabetes.
17 ClinVar pathogenic / likely pathogenic and 27 uncertain variants in ABCC8 have source records linked to Diabetes mellitus, permanent neonatal 3. Association strength is not clinical gene validity.
INS: Insulin
After processing to insulin, it lowers blood glucose by promoting cellular glucose uptake, glycogen and lipid synthesis, and suppression of hepatic glucose production. Pathogenic variants can cause neonatal diabetes, maturity-onset diabetes of the young, or hyperproinsulinemia depending on their effect on folding and secretion.
11 ClinVar pathogenic / likely pathogenic and 16 uncertain variants in INS have source records linked to Diabetes mellitus, permanent neonatal 3. Association strength is not clinical gene validity.
KCNJ11: ATP-sensitive inward rectifier potassium channel 11
Together with SUR1, its ATP-sensitive potassium conductance couples pancreatic beta-cell metabolism to membrane depolarization and insulin secretion. Activating variants cause neonatal diabetes, whereas loss-of-function variants can cause congenital hyperinsulinism.
7 ClinVar pathogenic / likely pathogenic and 11 uncertain variants in KCNJ11 have source records linked to Diabetes mellitus, permanent neonatal 3. Association strength is not clinical gene validity.
Where Diabetes mellitus, permanent neonatal 3 variants cluster
- ABCC8 ABC transporter 2 (positions 1344–1578): 8 of 17 ClinVar pathogenic / likely pathogenic variants, 3.2× more than its size predicts.
- KCNJ11 Cytoplasmic (positions 172–390): 6 of 7 ClinVar pathogenic / likely pathogenic variants, 1.5× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Diabetes mellitus, permanent neonatal 3
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCC8 R1352P | 1352 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1393C | 1393 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 P1413L | 1413 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1420C | 1420 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1493W | 1493 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| INS C96F | 96 | Pathogenic / likely pathogenic (★★) | |
| INS C96R | 96 | Pathogenic / likely pathogenic (★★) | |
| INS C96S | 96 | Pathogenic / likely pathogenic (★★) | |
| INS C96Y | 96 | Pathogenic / likely pathogenic (★★) | |
| ABCC8 R168C | 168 | Extracellular | Pathogenic / likely pathogenic (★★) |
| KCNJ11 E282K | 282 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ABCC8 V607M | 607 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ABCC8 R841G | 841 | ABC transporter 1 | Pathogenic / likely pathogenic (★★) |
| ABCC8 G1255S | 1255 | ABC transmembrane type-1 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 V187D | 187 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ABCC8 V1522M | 1522 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| KCNJ11 V59M | 59 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNJ11 E229K | 229 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ABCC8 M1V | 1 | Extracellular | Pathogenic / likely pathogenic (★★) |
| INS M1V | 1 | Pathogenic / likely pathogenic (★★) | |
| INS A24D | 24 | Pathogenic / likely pathogenic (★★) | |
| INS F48C | 48 | Pathogenic / likely pathogenic (★★) | |
| KCNJ11 R201L | 201 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| INS R89C | 89 | Pathogenic / likely pathogenic | |
| KCNJ11 R201H | 201 | Cytoplasmic | Pathogenic / likely pathogenic |
| INS R89P | 89 | Pathogenic / likely pathogenic | |
| KCNJ11 R201C | 201 | Cytoplasmic | Pathogenic / likely pathogenic |
| INS G32S | 32 | Pathogenic / likely pathogenic | |
| INS R89L | 89 | Pathogenic / likely pathogenic | |
| KCNJ11 R301H | 301 | Cytoplasmic | Pathogenic / likely pathogenic |
| ABCC8 I1423V | 1423 | ABC transporter 2 | Pathogenic / likely pathogenic |
| ABCC8 I1424V | 1424 | ABC transporter 2 | Pathogenic / likely pathogenic |
| ABCC8 L213R | 213 | Cytoplasmic | Pathogenic / likely pathogenic |
| ABCC8 E382K | 382 | ABC transmembrane type-1 1 | Pathogenic / likely pathogenic |
| ABCC8 V86G | 86 | Transmembrane | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Diabetes mellitus, permanent neonatal 3
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ABCC8 R1352H | 1352 | ABC transporter 2 | Conflicting reports (★) | +6: R1352P at the same position is pathogenic; REVEL 0.934 |
Which prediction tools work for Diabetes mellitus, permanent neonatal 3
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 97 out of 100
- PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 86 out of 100
- CATVariant: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 80 out of 100
- MetaLR: 76 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MutPred2: 74 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 58 out of 100
Same protein, different disease
- Hyperinsulinemic hypoglycemia, familial, 1 also has ClinVar records linked to ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (31 pathogenic / likely pathogenic).
- Type 2 diabetes mellitus also has ClinVar records linked to ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (27 pathogenic / likely pathogenic).
- Hereditary hyperinsulinism also has ClinVar records linked to ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (22 pathogenic / likely pathogenic).
- Familial hyperinsulinism also has ClinVar records linked to ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (20 pathogenic / likely pathogenic).
- Diabetes mellitus, transient neonatal, 2 also has ClinVar records linked to ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (19 pathogenic / likely pathogenic).
- Diabetes also has ClinVar records linked to INS variants; they fall partly in the same places as the Diabetes mellitus, permanent neonatal 3 variants (12 pathogenic / likely pathogenic).
- Hyperproinsulinemia also has ClinVar records linked to INS variants; they fall in the same places as the Diabetes mellitus, permanent neonatal 3 variants (6 pathogenic / likely pathogenic).
- MODY also has ClinVar records linked to INS variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (3 pathogenic / likely pathogenic).
- Diabetes also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (12 pathogenic / likely pathogenic).
- Hyperinsulinemic hypoglycemia, familial, 1 also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (7 pathogenic / likely pathogenic).
- Familial hyperinsulinism also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (6 pathogenic / likely pathogenic).
- Permanent neonatal diabetes mellitus also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (6 pathogenic / likely pathogenic).
- Type 2 diabetes mellitus also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, permanent neonatal 3 variants (6 pathogenic / likely pathogenic).
Diseases related to Diabetes mellitus, permanent neonatal 3
- Monogenic diabetes, also linked to ABCC8, INS and KCNJ11
- MODY, also linked to ABCC8, INS and KCNJ11
- Type 2 diabetes mellitus, also linked to ABCC8, INS and KCNJ11
- Diabetes, also linked to ABCC8, INS and KCNJ11
- Permanent neonatal diabetes mellitus, also linked to ABCC8, INS and KCNJ11
- Hyperinsulinemic hypoglycemia, familial, 1, also linked to ABCC8 and KCNJ11
- Familial hyperinsulinism, also linked to ABCC8 and KCNJ11
- Diabetes mellitus, transient neonatal, 2, also linked to ABCC8 and KCNJ11
- Atrial septal defect, also linked to ABCC8
- Pulmonary arterial hypertension, also linked to ABCC8
- Hereditary hyperinsulinism, also linked to ABCC8
- Type 1 diabetes mellitus, also linked to INS
Frequently asked questions
Which genes have records linked to Diabetes mellitus, permanent neonatal 3?
This view contains 3 analyzed proteins: ABCC8, INS, KCNJ11. 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 35 pathogenic or likely pathogenic variants, 32 variants of uncertain significance and 22 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. 1 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 116 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.
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