Diabetes mellitus, transient neonatal, 2: genes and variants
Diabetes mellitus, transient neonatal, 2 is linked to 2 analyzed proteins (ABCC8 and KCNJ11). 22 DNA variants are known to cause it; 204 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: diabetes mellitus, transient neonatal, 3
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 disease-causing and 153 uncertain variants in ABCC8 are linked to Diabetes mellitus, transient neonatal, 2.
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 disease-causing and 51 uncertain variants in KCNJ11 are linked to Diabetes mellitus, transient neonatal, 2.
Where Diabetes mellitus, transient neonatal, 2 variants cluster
- ABCC8 ABC transporter 2 (positions 1344–1578): 10 of 19 disease-causing changes, 3.5× more than its size predicts.
Known disease-causing variants in Diabetes mellitus, transient neonatal, 2
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCC8 R1352P | 1352 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1418H | 1418 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1420C | 1420 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1493W | 1493 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 G1554V | 1554 | ABC transporter 2 | Disease-causing (★★) |
| KCNJ11 R136C | 136 | Extracellular | Disease-causing (★★) |
| ABCC8 R74W | 74 | Transmembrane | Disease-causing (★★) |
| ABCC8 G1400R | 1400 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R825W | 825 | ABC transporter 1 | Disease-causing (★★) |
| ABCC8 R841G | 841 | ABC transporter 1 | Disease-causing (★★) |
| ABCC8 R1182W | 1182 | ABC transmembrane type-1 2 | Disease-causing (★★) |
| ABCC8 T1515M | 1515 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 V187D | 187 | Cytoplasmic | Disease-causing (★★) |
| ABCC8 D1471N | 1471 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 L1543P | 1543 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 M1V | 1 | Extracellular | Disease-causing (★★) |
| ABCC8 N188S | 188 | Cytoplasmic | Disease-causing (★★) |
| ABCC8 L1565P | 1565 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 G111R | 111 | Transmembrane | Disease-causing (★★) |
| KCNJ11 R201C | 201 | Cytoplasmic | Disease-causing |
| ABCC8 L582V | 582 | ABC transmembrane type-1 1 | Disease-causing |
| KCNJ11 G53R | 53 | Cytoplasmic | Disease-causing |
Uncertain variants in Diabetes mellitus, transient neonatal, 2 that look disease-causing
| 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
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- 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 is also caused by ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (31 disease-causing).
- Type 2 diabetes mellitus is also caused by ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (27 disease-causing).
- Hereditary hyperinsulinism is also caused by ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (22 disease-causing).
- Familial hyperinsulinism is also caused by ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (20 disease-causing).
- Diabetes mellitus, permanent neonatal 3 is also caused by ABCC8 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (17 disease-causing).
- Neonatal diabetes mellitus is also caused by KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (8 disease-causing).
- Diabetes mellitus, permanent neonatal 3 is also caused by KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (7 disease-causing).
- Hyperinsulinemic hypoglycemia, familial, 1 is also caused by KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (7 disease-causing).
- Diabetes mellitus is also caused by KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (6 disease-causing).
- Familial hyperinsulinism is also caused by KCNJ11 variants; they fall mostly in different places as the Diabetes mellitus, transient neonatal, 2 variants (6 disease-causing).
Diseases related to Diabetes mellitus, transient neonatal, 2
- Monogenic diabetes, also linked to ABCC8 and KCNJ11
- Maturity-onset diabetes of the young, also linked to ABCC8 and KCNJ11
- Type 2 diabetes mellitus, also linked to ABCC8 and KCNJ11
- Hyperinsulinemic hypoglycemia, familial, 1, also linked to ABCC8 and KCNJ11
- Diabetes mellitus, permanent neonatal 3, also linked to ABCC8 and KCNJ11
- Neonatal diabetes mellitus, also linked to ABCC8 and KCNJ11
- Familial hyperinsulinism, also linked to ABCC8 and KCNJ11
- Permanent neonatal diabetes mellitus, also linked to ABCC8 and KCNJ11
- 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
Frequently asked questions
Which genes are linked to Diabetes mellitus, transient neonatal, 2?
In CATVariant, Diabetes mellitus, transient neonatal, 2 is linked to 2 analyzed proteins: ABCC8 (ATP-binding cassette sub-family C member 8) and KCNJ11 (ATP-sensitive inward rectifier potassium channel 11).
How many genetic variants are linked to Diabetes mellitus, transient neonatal, 2?
231 variants: 22 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 204 are of uncertain significance or have conflicting reports.
Which uncertain variants in Diabetes mellitus, transient neonatal, 2 look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example KCNJ11 R136H and ABCC8 R1352H. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Diabetes mellitus, transient neonatal, 2?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 17 disease-causing and 9 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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