Diabetes mellitus, transient neonatal, 2: genes and variants
Explore variant evidence for Diabetes mellitus, transient neonatal, 2 across 2 analyzed proteins (ABCC8, KCNJ11). Linked ClinVar records include 22 pathogenic or likely pathogenic variants, 158 variants of uncertain significance and 46 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, transient neonatal, 2
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.
19 ClinVar pathogenic / likely pathogenic and 153 uncertain variants in ABCC8 have source records linked to Diabetes mellitus, transient neonatal, 2. 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.
3 ClinVar pathogenic / likely pathogenic and 51 uncertain variants in KCNJ11 have source records linked to Diabetes mellitus, transient neonatal, 2. Association strength is not clinical gene validity.
Where Diabetes mellitus, transient neonatal, 2 variants cluster
- ABCC8 ABC transporter 2 (positions 1344–1578): 10 of 19 ClinVar pathogenic / likely pathogenic variants, 3.5× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Diabetes mellitus, transient neonatal, 2
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCC8 R1352P | 1352 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1418H | 1418 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1420C | 1420 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1493W | 1493 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 G1554V | 1554 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| KCNJ11 R136C | 136 | Extracellular | Pathogenic / likely pathogenic (★★) |
| ABCC8 R74W | 74 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| ABCC8 G1400R | 1400 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R825W | 825 | ABC transporter 1 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R841G | 841 | ABC transporter 1 | Pathogenic / likely pathogenic (★★) |
| ABCC8 R1182W | 1182 | ABC transmembrane type-1 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 T1515M | 1515 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 V187D | 187 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ABCC8 D1471N | 1471 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 L1543P | 1543 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 M1V | 1 | Extracellular | Pathogenic / likely pathogenic (★★) |
| ABCC8 N188S | 188 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| ABCC8 L1565P | 1565 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCC8 G111R | 111 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| KCNJ11 R201C | 201 | Cytoplasmic | Pathogenic / likely pathogenic |
| ABCC8 L582V | 582 | ABC transmembrane type-1 1 | Pathogenic / likely pathogenic |
| KCNJ11 G53R | 53 | Cytoplasmic | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Diabetes mellitus, transient neonatal, 2
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| KCNJ11 R136H | 136 | Extracellular | Conflicting reports (★) | +6: R136C at the same position is pathogenic; REVEL 0.984 |
| 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, transient neonatal, 2
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 97 out of 100
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 80 out of 100
- SIFT: 80 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, transient neonatal, 2 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, transient neonatal, 2 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, transient neonatal, 2 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, transient neonatal, 2 variants (20 pathogenic / likely pathogenic).
- Diabetes mellitus, permanent neonatal 3 also has ClinVar records linked to ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (17 pathogenic / likely pathogenic).
- Diabetes also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (12 pathogenic / likely pathogenic).
- Diabetes mellitus, permanent neonatal 3 also has ClinVar records linked to KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (7 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, transient neonatal, 2 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, transient neonatal, 2 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, transient neonatal, 2 variants (6 pathogenic / likely pathogenic).
Diseases related to Diabetes mellitus, transient neonatal, 2
- Monogenic diabetes, also linked to ABCC8 and KCNJ11
- MODY, also linked to ABCC8 and KCNJ11
- Hyperinsulinemic hypoglycemia, familial, 1, also linked to ABCC8 and KCNJ11
- Type 2 diabetes mellitus, also linked to ABCC8 and KCNJ11
- Diabetes, also linked to ABCC8 and KCNJ11
- Diabetes mellitus, permanent neonatal 3, also linked to ABCC8 and KCNJ11
- Familial hyperinsulinism, also linked to ABCC8 and KCNJ11
- Permanent neonatal diabetes mellitus, 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
- Leucine-induced hypoglycemia, also linked to ABCC8
Frequently asked questions
Which genes have records linked to Diabetes mellitus, transient neonatal, 2?
This view contains 2 analyzed proteins: ABCC8, 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 22 pathogenic or likely pathogenic variants, 158 variants of uncertain significance and 46 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. 2 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 231 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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