Diabetes Mellitus, Permanent Neonatal, 4 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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Aliases & Classifications for Diabetes Mellitus, Permanent Neonatal, 4

MalaCards integrated aliases for Diabetes Mellitus, Permanent Neonatal, 4:

Name: Diabetes Mellitus, Permanent Neonatal, 4 ⁵⁷

Diabetes Mellitus, Permanent Neonatal 4 ⁵⁷ ⁷³

Permanent Neonatal Diabetes Mellitus 4 ²⁹ ⁶

Pndm4 ⁵⁷ ⁷³

Characteristics:

OMIM®:

⁵⁷ (Updated 05-Mar-2021)

Inheritance:
autosomal dominant
autosomal recessive (in 1 patient)

Miscellaneous:
germline mosaicism has been reported
median age of diagnosis 9-11 weeks (majority diagnosed before age 6 months)
homozygous mutations have been reported

HPO:

³¹

diabetes mellitus, permanent neonatal, 4:
Inheritance autosomal dominant inheritance autosomal recessive inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Neuronal diseases Endocrine diseases Gastrointestinal diseases Muscle diseases

See all MalaCards categories (disease lists)

External Ids:

OMIM® ⁵⁷ 618858

OMIM Phenotypic Series ⁵⁷ PS606176

MeSH ⁴⁴ D003920

MedGen ⁴¹ C5394307 CN280870

SNOMED-CT via HPO ⁶⁸ 237598005 258211005 263681008 more

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Summaries for Diabetes Mellitus, Permanent Neonatal, 4

UniProtKB/Swiss-Prot : ⁷³ Diabetes mellitus, permanent neonatal 4: A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. PNDM4 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance.

MalaCards based summary : Diabetes Mellitus, Permanent Neonatal, 4, also known as diabetes mellitus, permanent neonatal 4, is related to hyperproinsulinemia and maturity-onset diabetes of the young. An important gene associated with Diabetes Mellitus, Permanent Neonatal, 4 is INS (Insulin), and among its related pathways/superpathways are AMP-activated Protein Kinase (AMPK) Signaling and Type II diabetes mellitus. Related phenotypes are type i diabetes mellitus and small for gestational age

OMIM® : ⁵⁷ Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life (summary by Polak et al., 2008). For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176). (618858) (Updated 05-Mar-2021)

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Related Diseases for Diabetes Mellitus, Permanent Neonatal, 4

Diseases in the Permanent Neonatal Diabetes Mellitus family:

Diabetes Mellitus, Permanent Neonatal, 1	Diabetes Mellitus, Permanent Neonatal, 2
Diabetes Mellitus, Permanent Neonatal, 3	Diabetes Mellitus, Permanent Neonatal, 4

Diseases related to Diabetes Mellitus, Permanent Neonatal, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

#	Related Disease	Score	Top Affiliating Genes
1	hyperproinsulinemia	9.8	INS-IGF2 INS
2	maturity-onset diabetes of the young	9.7	INS-IGF2 INS
3	maturity-onset diabetes of the young, type 10	9.7	INS-IGF2 INS
4	type 1 diabetes mellitus 2	9.7	INS-IGF2 INS
5	monogenic diabetes	9.7	INS-IGF2 INS
6	permanent neonatal diabetes mellitus	9.7	INS-IGF2 INS
7	neonatal diabetes	9.6	INS-IGF2 INS
8	diabetes mellitus, permanent neonatal, 1	9.6	INS-IGF2 INS
9	beckwith-wiedemann syndrome	9.5	INS-IGF2 INS

Graphical network of the top 20 diseases related to Diabetes Mellitus, Permanent Neonatal, 4:

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Symptoms & Phenotypes for Diabetes Mellitus, Permanent Neonatal, 4

Human phenotypes related to Diabetes Mellitus, Permanent Neonatal, 4:

³¹ (show all 6)

#	Description	HPO Source Accession
1	type i diabetes mellitus ³¹	HP:0100651
2	small for gestational age ³¹	HP:0001518
3	hyperglycemia ³¹	HP:0003074
4	elevated hemoglobin a1c ³¹	HP:0040217
5	diabetic ketoacidosis ³¹	HP:0001953
6	reduced c-peptide level ³¹	HP:0030795

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 05-Mar-2021)

Growth Other:
failure to thrive
small for gestational age

Head And Neck Eyes:
retinopathy

Laboratory Abnormalities:
hyperglycemia
ketoacidosis
elevated hemoglobin a1c
ketosis
negative insulin autoantibodies
more

Neurologic Peripheral Nervous System:
neuropathy

Growth Weight:
reduced birth weight

Metabolic Features:
polydipsia

Skin Nails Hair Skin:
acanthosis nigricans

Genitourinary Kidneys:
polyuria

Endocrine Features:
neonatal diabetes mellitus

Cardiovascular Vascular:
diabetic macroangiopathy

Clinical features from OMIM®:

618858 (Updated 05-Mar-2021)

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Drugs & Therapeutics for Diabetes Mellitus, Permanent Neonatal, 4

Search Clinical Trials , NIH Clinical Center for Diabetes Mellitus, Permanent Neonatal, 4

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Genetic Tests for Diabetes Mellitus, Permanent Neonatal, 4

Genetic tests related to Diabetes Mellitus, Permanent Neonatal, 4:

#	Genetic test	Affiliating Genes
1	Permanent Neonatal Diabetes Mellitus 4 ²⁹	INS

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Anatomical Context for Diabetes Mellitus, Permanent Neonatal, 4

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Publications for Diabetes Mellitus, Permanent Neonatal, 4

Articles related to Diabetes Mellitus, Permanent Neonatal, 4:

#	Title	Authors	PMID	Year
1	Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism. ⁵⁷ ⁶	Carmody D...Greeley SA	26101329	2015
2	Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. ⁵⁷ ⁶	Colombo C...Early Onset Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (SIEDP)	18451997	2008
3	Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group. ⁵⁷ ⁶	Polak M...French ND (Neonatal Diabetes) Study Group	18171712	2008
4	Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. ⁵⁷ ⁶	Edghill EL...Ellard S	18162506	2008
5	Insulin gene mutations as a cause of permanent neonatal diabetes. ⁶ ⁵⁷	Stoy J...Neonatal Diabetes International Collaborative Group	17855560	2007

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Genes for Diabetes Mellitus, Permanent Neonatal, 4

Genes related to Diabetes Mellitus, Permanent Neonatal, 4 (2 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	INS	Insulin	Protein Coding	918.85	Molecular basis known ⁵⁷ Causative variation ⁷³ Genetic Tests ²⁹ GeneCards inferred via : Disorders Variants (show sections)
2	INS-IGF2	INS-IGF2 Readthrough	Protein Coding	400	Pathogenic ⁶	17855560 18162506 18171712 (more) 18451997 26101329

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Variations for Diabetes Mellitus, Permanent Neonatal, 4

ClinVar genetic disease variations for Diabetes Mellitus, Permanent Neonatal, 4:

⁶

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	INS-IGF2	NM_000207.3(INS):c.187+241G>A	SNV	Pathogenic	268153	rs886041083	11:2181774-2181774	11:2160544-2160544
2	INS-IGF2	NM_000207.3(INS):c.94G>A (p.Gly32Ser)	SNV	Pathogenic	21122	rs80356664	11:2182108-2182108	11:2160878-2160878
3	INS-IGF2	NM_000207.3(INS):c.127T>G (p.Cys43Gly)	SNV	Pathogenic	21114	rs80356666	11:2182075-2182075	11:2160845-2160845
4	INS-IGF2	NM_000207.3(INS):c.265C>T (p.Arg89Cys)	SNV	Pathogenic	21117	rs80356669	11:2181150-2181150	11:2159920-2159920
5	INS-IGF2	NM_000207.3(INS):c.287G>A (p.Cys96Tyr)	SNV	Pathogenic	13387	rs80356671	11:2181128-2181128	11:2159898-2159898
6	INS-IGF2	NM_000207.3(INS):c.71C>A (p.Ala24Asp)	SNV	Pathogenic	13388	rs80356663	11:2182131-2182131	11:2160901-2160901
7	INS-IGF2	NM_000207.3(INS):c.143T>G (p.Phe48Cys)	SNV	Pathogenic	13389	rs80356668	11:2182059-2182059	11:2160829-2160829

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Permanent Neonatal, 4:

⁷³ (show all 15)

#	Symbol	AA change	Variation ID	SNP ID
1	INS	p.Ala24Asp	VAR_063723	rs80356663
2	INS	p.His29Asp	VAR_063724	rs121908272
3	INS	p.Gly32Arg	VAR_063725	rs80356664
4	INS	p.Gly32Ser	VAR_063726	rs80356664
5	INS	p.Leu35Pro	VAR_063727	rs121908273
6	INS	p.Cys43Gly	VAR_063728	rs80356666
7	INS	p.Gly47Val	VAR_063730	rs80356667
8	INS	p.Phe48Cys	VAR_063731	rs80356668
9	INS	p.Arg89Cys	VAR_063735	rs80356669
10	INS	p.Gly90Cys	VAR_063736	rs80356670
11	INS	p.Cys96Ser	VAR_063737	rs80356671
12	INS	p.Cys96Tyr	VAR_063738	rs80356671
13	INS	p.Ser101Cys	VAR_063739	rs121908276
14	INS	p.Tyr103Cys	VAR_063740	rs121908277
15	INS	p.Tyr108Cys	VAR_063741	rs80356672

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Expression for Diabetes Mellitus, Permanent Neonatal, 4

Search GEO for disease gene expression data for Diabetes Mellitus, Permanent Neonatal, 4.

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Pathways for Diabetes Mellitus, Permanent Neonatal, 4

Pathways related to Diabetes Mellitus, Permanent Neonatal, 4 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	AMP-activated Protein Kinase (AMPK) Signaling ¹ Show member pathways AMPK signaling pathway ³⁶ AMPK Signaling Pathway ⁶⁶	11.41	INS-IGF2 INS
2	Type II diabetes mellitus ³⁶ ¹ Show member pathways Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics ⁶⁰	10.61	INS-IGF2 INS

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GO Terms for Diabetes Mellitus, Permanent Neonatal, 4

Molecular functions related to Diabetes Mellitus, Permanent Neonatal, 4 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	hormone activity	GO:0005179	8.62	INS-IGF2 INS

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Sources for Diabetes Mellitus, Permanent Neonatal, 4

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⁷¹ UMLS

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⁷⁴ Wikipedia

Diabetes Mellitus, Permanent Neonatal, 4 (PNDM4)

Aliases & Classifications for Diabetes Mellitus, Permanent Neonatal, 4

MalaCards integrated aliases for Diabetes Mellitus, Permanent Neonatal, 4:

Characteristics:

OMIM®:

HPO:

Classifications:

External Ids:

Summaries for Diabetes Mellitus, Permanent Neonatal, 4

Related Diseases for Diabetes Mellitus, Permanent Neonatal, 4

Diseases in the Permanent Neonatal Diabetes Mellitus family:

Diseases related to Diabetes Mellitus, Permanent Neonatal, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

Graphical network of the top 20 diseases related to Diabetes Mellitus, Permanent Neonatal, 4:

Symptoms & Phenotypes for Diabetes Mellitus, Permanent Neonatal, 4

Human phenotypes related to Diabetes Mellitus, Permanent Neonatal, 4:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

Drugs & Therapeutics for Diabetes Mellitus, Permanent Neonatal, 4

Genetic Tests for Diabetes Mellitus, Permanent Neonatal, 4

Genetic tests related to Diabetes Mellitus, Permanent Neonatal, 4:

Anatomical Context for Diabetes Mellitus, Permanent Neonatal, 4

Publications for Diabetes Mellitus, Permanent Neonatal, 4

Articles related to Diabetes Mellitus, Permanent Neonatal, 4:

Genes for Diabetes Mellitus, Permanent Neonatal, 4

Genes related to Diabetes Mellitus, Permanent Neonatal, 4 (2 elite genes):

Variations for Diabetes Mellitus, Permanent Neonatal, 4

ClinVar genetic disease variations for Diabetes Mellitus, Permanent Neonatal, 4:

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Permanent Neonatal, 4:

Expression for Diabetes Mellitus, Permanent Neonatal, 4

Pathways for Diabetes Mellitus, Permanent Neonatal, 4

Pathways related to Diabetes Mellitus, Permanent Neonatal, 4 according to GeneCards Suite gene sharing:

GO Terms for Diabetes Mellitus, Permanent Neonatal, 4

Molecular functions related to Diabetes Mellitus, Permanent Neonatal, 4 according to GeneCards Suite gene sharing:

Sources for Diabetes Mellitus, Permanent Neonatal, 4