# Diabetes mellitus genéticos raros

> Página oficial: https://raras.org/doenca/diabetes-mellitus-geneticos-raros
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 183625 — https://www.orpha.net/en/disease/detail/183625
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Diabetes mellitus causado por mutações em um único gene.

## Epidemiologia e herança


## Sinais e sintomas (201 fenótipos HPO)

- **Escoliose toracolombar** — HPO: HP:0002944
- **Síndrome de Fanconi renal** — HPO: HP:0001994
- **Ducto deferente atrésico** — HPO: HP:0030997
- **Contratura das articulações dos membros inferiores** — HPO: HP:0005750
- **Obesidade** — HPO: HP:0001513
- **Apneia** — HPO: HP:0002104
- **Anormalidade dos membros** — HPO: HP:0040064
- **Raquitismo** — HPO: HP:0002748
- **Sobrepeso** — HPO: HP:0025502
- **Anormalidade do nível de fosfatase alcalina** — HPO: HP:0004379
- **Ataxia** — HPO: HP:0001251
- **Orelhas de implantação baixa** — HPO: HP:0000369
- **Diabetes tipo MODY (Maturity-Onset Diabetes of the Young)** — HPO: HP:0004904
- **Tolerância à glicose prejudicada** — HPO: HP:0040270
- **Esteatose hepática** — HPO: HP:0001397
- **Aminoacidúria** — HPO: HP:0003355
- **Atetose** — HPO: HP:0002305
- **Lesão renal aguda** — HPO: HP:0001919
- **Hipouricemia** — HPO: HP:0003537
- **Hiperuricemia** — HPO: HP:0002149
- **Concentração elevada de fosfatase alcalina circulante** — HPO: HP:0003155
- **Fontanela anterior ampla** — HPO: HP:0000260
- **Pectus carinatum** — HPO: HP:0000768
- **Atividade epileptiforme interictal** — HPO: HP:0011182
- **Macroglossia** — HPO: HP:0000158
- **Atraso motor** — HPO: HP:0001270
- **Coma** — HPO: HP:0001259
- **Contratura em flexão** — HPO: HP:0001371
- **Acidemia** — HPO: HP:0032368
- **Insuficiência pancreática exócrina** — HPO: HP:0001738
- **Fibrose hepática** — HPO: HP:0001395
- **Déficit de crescimento** — HPO: HP:0001508
- **Artrite** — HPO: HP:0001369
- **Intolerância à glicose** — HPO: HP:0001952
- **Dedos sobrepostos** — HPO: HP:0010557
- **Deficiência intelectual** — HPO: HP:0001249
- **Rim em ferradura** — HPO: HP:0000085
- **Hemoglobina A1c elevada** — HPO: HP:0040217
- **Agenesia renal unilateral** — HPO: HP:0000122
- **Hipotireoidismo** — HPO: HP:0000821
- _...e mais 161 sintomas. Ver https://raras.org/doenca/diabetes-mellitus-geneticos-raros._

## Genes associados (22)

- **GCK** — Mitogen-activated protein kinase kinase kinase kinase 2 [Disease-causing germline mutation(s) in]
  - Função: Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stre
- **HNF1A** — Hepatocyte nuclear factor 1-alpha [Disease-causing germline mutation(s) in]
  - Função: Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (By similarity). Binds to the inverted palindrome 5'-GTTAAT
- **KCNJ11** — ATP-sensitive inward rectifier potassium channel 11 [Disease-causing germline mutation(s) in]
  - Função: Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many dif
- **HNF4A** — Hepatocyte nuclear factor 4-alpha [Disease-causing germline mutation(s) in]
  - Função: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promot
- **CEL** — Bile salt-activated lipase [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the hydrolysis of a wide range of substrates including cholesteryl esters, phospholipids, lysophospholipids, di- and tri-acylglycerols, and fatty acid esters of hydroxy fatty acids (FAHFAs)
- **NARS2** — Asparaginyl-tRNA synthetase [Candidate gene tested in]
  - Função: Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the asparagine amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis (PubM
- **PDX1** — Pancreas/duodenum homeobox protein 1 [Disease-causing germline mutation(s) in]
  - Função: Activates insulin, somatostatin, glucokinase, islet amyloid polypeptide and glucose transporter type 2 gene transcription. Particularly involved in glucose-dependent regulation of insulin gene transcr
- **ZFP57** — Zinc finger protein 57 homolog [Disease-causing germline mutation(s) in]
  - Função: Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of
- **KLF11** — Krueppel-like factor 11 [Disease-causing germline mutation(s) in]
  - Função: Transcription factor (PubMed:10207080, PubMed:9748269). Activates the epsilon- and gamma-globin gene promoters and, to a much lower degree, the beta-globin gene and represses promoters containing SP1-
- **APPL1** — DCC-interacting protein 13-alpha [Candidate gene tested in]
  - Função: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal traf
- **GLIS3** — Zinc finger protein GLIS3 [Disease-causing germline mutation(s) in]
  - Função: Acts both as a repressor and an activator of transcription. Binds to the consensus sequence 5'-GACCACCCAC-3' (By similarity)
- **PAX4** — Paired box protein Pax-4 [Disease-causing germline mutation(s) in]
  - Função: Plays an important role in the differentiation and development of pancreatic islet beta cells. Transcriptional repressor that binds to a common element in the glucagon, insulin and somatostatin promot
- **HNF1B** — Hepatocyte nuclear factor 1-beta [Disease-causing germline mutation(s) in]
  - Função: Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:17924661, PubMed:7900999). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity).
- **PTF1A** — Pancreas transcription factor 1 subunit alpha [Disease-causing germline mutation(s) in]
  - Função: Transcription factor implicated in the cell fate determination in various organs. Binds to the E-box consensus sequence 5'-CANNTG-3'. Plays a role in early and late pancreas development and differenti
- **INS** — Insulin [Disease-causing germline mutation(s) in]
  - Função: Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt

## Ensaios clínicos ativos (5)

- **NCT05007990** [RECRUITING]: Caregiving Networks Across Disease Context and the Life Course — https://clinicaltrials.gov/study/NCT05007990
- **NCT06478121** [RECRUITING]: Understanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE) — https://clinicaltrials.gov/study/NCT06478121
- **NCT03366337** [COMPLETED]: A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX — https://clinicaltrials.gov/study/NCT03366337
- **NCT01793168** [RECRUITING]: Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford — https://clinicaltrials.gov/study/NCT01793168
- **NCT03655223** [ENROLLING_BY_INVITATION]: Early Check: Expanded Screening in Newborns — https://clinicaltrials.gov/study/NCT03655223

## Doenças relacionadas (por similaridade fenotípica)

- [Diabetes mellitus neonatal](https://raras.org/doenca/224) — ORPHA:224 — 128 sintomas em comum
- [Síndrome MODY](https://raras.org/doenca/sindrome-mody) — ORPHA:552 — 98 sintomas em comum
- [Diabetes mellitus neonatal permanente isolado](https://raras.org/doenca/diabetes-mellitus-neonatal-permanente-isolado) — ORPHA:99885 — 62 sintomas em comum
- [Doença túbulo-intersticial renal autossômica dominante HNF1B-relacionada](https://raras.org/doenca/doenca-tubulo-intersticial-renal-autossomica-dominante-hnf1b-relacionada) — ORPHA:93111 — 57 sintomas em comum
- [Alteração do metabolismo e excreção de bilirrubina](https://raras.org/doenca/alteracao-do-metabolismo-e-excrecao-de-bilirrubina) — ORPHA:309816 — 45 sintomas em comum
- [Cistinose](https://raras.org/doenca/cistinose) — ORPHA:213 — 41 sintomas em comum
- [Hipoglicemia hiperinsulinêmica](https://raras.org/doenca/hipoglicemia-hiperinsulinemica) — ORPHA:443095 — 41 sintomas em comum
- [Deficiência de complexo III isolada](https://raras.org/doenca/deficiencia-de-complexo-iii-isolada) — ORPHA:1460 — 38 sintomas em comum
- [Acidemia metilmalônica com homocistinúria](https://raras.org/doenca/acidemia-metilmalonica-com-homocistinuria) — ORPHA:26 — 37 sintomas em comum
- [Síndrome de diabetes neonatal-hipotireoidismo congênito-glaucoma congênito-fibrose hepática-rins policísticos](https://raras.org/doenca/sindrome-de-diabetes-neonatal-hipotireoidismo-congenito-glaucoma-congenito-fibrose-hepatica-rins-policisticos) — ORPHA:79118 — 37 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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