MCID: EPP024
MIFTS: 47

Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus

Categories: Genetic diseases, Rare diseases, Bone diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

MalaCards integrated aliases for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

Name: Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus 57
Wolcott-Rallison Syndrome 57 12 59 75 37 13 55 15 40 73
Med-Iddm Syndrome 57 53 75
Iddm-Med Syndrome 57 53 75
Wrs 59 75
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 53
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 59
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 75
Wolcott Rallison Syndrome 53

Characteristics:

Orphanet epidemiological data:

59
wolcott-rallison syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset of diabetes in neonatal period/ early infancy
onset of epiphyseal dysplasia and growth retardation in first 2 years of life


HPO:

32
epiphyseal dysplasia, multiple, with early-onset diabetes mellitus:
Mortality/Aging death in infancy
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1667Disease definitionWolcott-Rallison syndrome (WRS) is a very rare genetic disease, characterized by permanent neonatal diabetes mellitus (PNDM) with multiple epiphyseal dysplasia and other clinical manifestations, including recurrent episodes of acute liver failure.EpidemiologyFewer than 60 cases have been reported to date. Most patients are from consanguineous families. Prevalence may therefore vary significantly between countries.WRS may be underdiagnosed because of early death before diagnosis.Clinical descriptionDiabetes occurs early, generally before six months of age, is permanent and insulin-dependent from the onset. Skeletal dysplasia generally manifests within the 1st or 2nd year of life, and is associated with short stature (dwarfism with short trunk). Deficient mineralization or dysplastic changes, affecting the long bones, pelvis and vertebrae, but usually not the skull, may be seen on radiography as early as diabetes onset. Hepatic dysfunction is a 3rd characteristic feature and the most life-threatening complication, and manifests by elevated hepatic enzymes, liver enlargement and recurrent acute liver failure. Other manifestations vary between patients in type and severity and include renal dysfunction, exocrine pancreas insufficiency, intellectual deficit, hypothyroidism, neutropenia and recurrent infections. Clinical course is variable, including within the same sibship.EtiologyWRS is caused by mutations in the EIF2AK3 gene encoding eukaryotic translation initiation factor 2-alpha kinase 3 (PKR-like endoplasmic reticulum kinase; PERK), which plays a key role in translation control during unfolded protein response.Diagnostic methodsDiagnosis should be suspected in any infant with permanent neonatal diabetes and skeletal dysplasia and/or episodes of acute liver failure, and family history of consanguinity and/or neonatal diabetes. Diabetes is not autoimmune as shown by absence of antibodies specific for type 1 diabetes. Radiographs show early signs of multiple epiphyseal dysplasia and deficient mineralization. Molecular genetic testing confirms the diagnosis.Differential diagnosisDifferential diagnosis is based on clinical presentation and, ultimately, genetic testing. That of NDM (see this term) includes transient NDM, and other PNDMs that may be isolated or syndromic. Differential diagnosis of skeletal dysplasia includes other spondylo-epiphyseal dysplasias such as mucopolysaccharidoses (see these terms) where diabetes may occur independently at an older age.Antenatal diagnosisAntenatal diagnosis should be offered to parents of a WRS patient with confirmed EIF2AK3 mutation.Genetic counselingInheritance is autosomal recessive and genetic counseling is possible.Management and treatmentClose therapeutic monitoring of diabetes should be considered and treatment with an insulin pump is recommended, especially in the first months of life, due to the risk of acute episodes of hypoglycemia. At any age, hypoglycemia should be prevented because the disease can decompensate, even if this requires maintaining the level of glucose above the objectives generally recommended in diabetic children. General anesthesia increases the risk of acute aggravation, because of particular sensitivity of patients to anesthetics, and should be avoided wherever possible. Any drug or vaccine not strictly necessary should be limited, due to the risk of triggering secondary liver and/or kidney failure.PrognosisPrognosis is poor and most patients die at a young age from multiple-organ failure with predominant liver and renal dysfunction.Visit the Orphanet disease page for more resources.

MalaCards based summary : Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus, also known as wolcott-rallison syndrome, is related to neonatal diabetes mellitus and diabetes mellitus, permanent neonatal. An important gene associated with Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus is EIF2AK3 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3), and among its related pathways/superpathways are Protein processing in endoplasmic reticulum and Potassium Channels. Affiliated tissues include bone, pancreas and liver, and related phenotypes are genu valgum and hypothyroidism

OMIM : 57 Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis, and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, mental retardation, and cardiovascular abnormalities (summary by Delepine et al., 2000). (226980)

UniProtKB/Swiss-Prot : 75 Wolcott-Rallison syndrome: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities.

Disease Ontology : 12 A characterized by autosomal recessive inheritance of permanent neonatal diabetes mellitus with multiple epiphyseal dysplasia, osteoporosis, growth retardation and frequently hepatic and renal dysfunction that has material basis in homozygous mutation in the EIF2AK3 gene on chromosome 2p11.2.

Wikipedia : 76 Wolcott–Rallison syndrome, WRS, is a rare, autosomal recessive disorder with infancy-onset diabetes... more...

Related Diseases for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Diseases related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
# Related Disease Score Top Affiliating Genes
1 neonatal diabetes mellitus 29.8 ABCC8 EIF2AK3 KCNJ11
2 diabetes mellitus, permanent neonatal 28.9 ABCC8 EIF2AK3 IER3IP1 KCNJ11
3 blood group--wright antigen 11.5
4 blood group, diego system 11.2
5 long qt syndrome 1 11.2
6 diabetes mellitus 10.5
7 hypothyroidism 10.3
8 renal dysplasia, cystic 10.2
9 infantile liver failure syndrome 1 10.2
10 acute liver failure 10.2
11 hepatitis 10.2
12 liver disease 10.2
13 hypoaldosteronism 10.2
14 multicystic dysplastic kidney 10.2
15 spinal muscular atrophy 10.0
16 muscular atrophy 10.0
17 munchausen by proxy 10.0 ABCC8 KCNJ11
18 cardiomyopathy, dilated, 1o 10.0 ABCC8 KCNJ11
19 factitious disorder 9.9 ABCC8 KCNJ11
20 hyperinsulinemic hypoglycemia, familial, 2 9.9 ABCC8 KCNJ11
21 acute insulin response 9.9 ABCC8 KCNJ11
22 usher syndrome, type ic 9.9 ABCC8 KCNJ11
23 cantu syndrome 9.9 ABCC8 KCNJ11
24 monogenic diabetes 9.9 ABCC8 KCNJ11
25 acquired metabolic disease 9.9 IER3IP1 KCNJ11
26 pancreatic agenesis 9.8 ABCC8 KCNJ11
27 prostate cancer 9.8
28 progeroid syndrome, neonatal 9.8
29 malaria 9.8
30 cutaneous leishmaniasis 9.8
31 plasmodium vivax malaria 9.8
32 prostatitis 9.8
33 leishmaniasis 9.8
34 endocrine pancreas disease 9.8 ABCC8 KCNJ11
35 pancreas disease 9.8 ABCC8 KCNJ11
36 diabetes mellitus, transient neonatal, 1 9.8 ABCC8 KCNJ11
37 hyperinsulinemic hypoglycemia 9.7 ABCC8 KCNJ11
38 hyperinsulinism 9.6 ABCC8 KCNJ11
39 hyperglycemia 9.5 ABCC8 KCNJ11
40 glucose metabolism disease 9.4 ABCC8 IER3IP1 KCNJ11
41 hypoglycemia 9.2 ABCC8 KCNJ11

Graphical network of the top 20 diseases related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:



Diseases related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus

Symptoms & Phenotypes for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
upslanting palpebral fissures

Abdomen Liver:
hepatomegaly

Head And Neck Head:
microcephaly

Neurologic Central Nervous System:
hypertonia
developmental delay

Skeletal:
osteoporosis
multiple epiphyseal dysplasia

Skeletal Pelvis:
coxa valga
hip dislocation
narrow iliac wings
hip subluxation
reabsorption of capital femoral epiphyses

Abdomen Pancreas:
reduced pancreatic beta cells

Head And Neck Ears:
preauricular pits

Skeletal Feet:
ivory epiphyses
small, irregular tarsal centers
hypoplastic middle and distal phalanges

Skeletal Limbs:
genu valgum
bowing distal radii and ulnae
small, flattened epiphyses

Head And Neck Nose:
depressed nasal bridge

Growth Height:
short stature

Genitourinary Kidneys:
renal insufficiency

Skeletal Spine:
platyspondyly
lordosis
odontoid hypoplasia
irregular endplates

Chest External Features:
barrel-shaped chest

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
small, irregular carpal centers
cone-shaped epiphyses (proximal phalanges)
ivory epiphyses
disproportionately short middle phalanges

Endocrine Features:
insulin-dependent diabetes mellitus (onset in infancy)


Clinical features from OMIM:

226980

Human phenotypes related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

59 32 (show top 50) (show all 83)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 genu valgum 59 32 frequent (33%) Frequent (79-30%) HP:0002857
2 hypothyroidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000821
3 osteopenia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000938
4 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
5 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
6 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
7 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
8 kyphosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002808
9 hyperlordosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003307
10 hepatomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0002240
11 delayed skeletal maturation 59 32 frequent (33%) Frequent (79-30%) HP:0002750
12 microcephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000252
13 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
14 renal insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000083
15 nephropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000112
16 renal tubular dysfunction 59 32 hallmark (90%) Very frequent (99-80%) HP:0000124
17 dehydration 59 32 hallmark (90%) Very frequent (99-80%) HP:0001944
18 osteoporosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000939
19 hypoglycemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001943
20 hyperuricemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002149
21 weight loss 59 32 hallmark (90%) Very frequent (99-80%) HP:0001824
22 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000944
23 epiphyseal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002656
24 platyspondyly 59 32 frequent (33%) Frequent (79-30%) HP:0000926
25 coxa valga 59 32 frequent (33%) Frequent (79-30%) HP:0002673
26 epicanthus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000286
27 short thorax 59 32 frequent (33%) Frequent (79-30%) HP:0010306
28 microdontia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000691
29 enlarged thorax 59 32 frequent (33%) Frequent (79-30%) HP:0100625
30 intrauterine growth retardation 59 32 occasional (7.5%) Occasional (29-5%) HP:0001511
31 elevated hepatic transaminases 59 32 frequent (33%) Frequent (79-30%) HP:0002910
32 jaundice 59 32 occasional (7.5%) Occasional (29-5%) HP:0000952
33 exocrine pancreatic insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0001738
34 abnormality of neuronal migration 59 32 occasional (7.5%) Occasional (29-5%) HP:0002269
35 hip dislocation 59 32 frequent (33%) Frequent (79-30%) HP:0002827
36 brachydactyly 59 32 frequent (33%) Frequent (79-30%) HP:0001156
37 coma 59 32 very rare (1%) Very rare (<4-1%) HP:0001259
38 recurrent fractures 59 32 occasional (7.5%) Occasional (29-5%) HP:0002757
39 neutropenia 59 32 frequent (33%) Frequent (79-30%) HP:0001875
40 acute hepatic failure 59 32 frequent (33%) Frequent (79-30%) HP:0006554
41 high forehead 59 32 hallmark (90%) Very frequent (99-80%) HP:0000348
42 thin vermilion border 59 32 hallmark (90%) Very frequent (99-80%) HP:0000233
43 triangular face 59 32 hallmark (90%) Very frequent (99-80%) HP:0000325
44 narrow iliac wings 59 32 frequent (33%) Frequent (79-30%) HP:0002868
45 motor delay 59 32 frequent (33%) Frequent (79-30%) HP:0001270
46 cone-shaped epiphyses of the phalanges of the hand 59 32 hallmark (90%) Very frequent (99-80%) HP:0010230
47 glycosuria 59 32 hallmark (90%) Very frequent (99-80%) HP:0003076
48 chronic hepatic failure 59 32 frequent (33%) Frequent (79-30%) HP:0100626
49 steatorrhea 59 32 hallmark (90%) Very frequent (99-80%) HP:0002570
50 abnormal heart morphology 59 32 frequent (33%) Frequent (79-30%) HP:0001627

Drugs & Therapeutics for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Search Clinical Trials , NIH Clinical Center for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus

Genetic Tests for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Anatomical Context for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

MalaCards organs/tissues related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

41
Bone, Pancreas, Liver, Kidney, Testes, Heart

Publications for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Articles related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

(show all 36)
# Title Authors Year
1
A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Patients with Neonatal Diabetes. ( 28843469 )
2017
2
Ketoacidosis in Neonatal Diabetes Mellitus, Part of Wolcott-Rallison Syndrome. ( 28652565 )
2017
3
Multicystic dysplastic kidney: a new association of Wolcott-Rallison syndrome. ( 28955442 )
2017
4
Novel splice site mutation in EIF2AK3 gene causes Wolcott-Rallison syndrome in a consanguineous family from Saudi Arabia. ( 28220546 )
2017
5
En bloc multiorgan transplant (liver, pancreas, and kidney) for acute liver and renal failure in a patient with wolcott-rallison syndrome. ( 26784269 )
2016
6
Wolcott-Rallison syndrome with novel EIF2AK3 gene mutation. ( 27145240 )
2016
7
Os odontoideum in wolcott-rallison syndrome: a case series of 4 patients. ( 26860746 )
2016
8
Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort. ( 25659842 )
2015
9
RelatA+ve hypoaldosteronism in a patient with Wolcott-Rallison syndrome. ( 26433138 )
2015
10
Anaesthesia and orphan disease: a child with Wolcott-Rallison syndrome. ( 25101713 )
2015
11
Novel mutation in wolcott-rallison syndrome with variable expression in two omani siblings. ( 25960841 )
2015
12
Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison syndrome. ( 25384546 )
2015
13
Wolcott Rallison syndrome: a rare inherited diabetes mellitus. ( 24710710 )
2014
14
Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome. ( 24859506 )
2014
15
Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases. ( 25131821 )
2014
16
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. ( 23759358 )
2013
17
Primary hypothyroidism: an unusual manifestation of Wolcott-Rallison syndrome. ( 23933668 )
2013
18
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. ( 28156240 )
2013
19
EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome. ( 24168455 )
2013
20
Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome. ( 24194294 )
2013
21
Variable phenotype in five patients with Wolcott-Rallison syndrome due to the same EIF2AK3 (c.1259delA) mutation. ( 23585173 )
2013
22
Recurrent Hepatitis in Two Iranian Children: A Novel (Q166R) Mutation in EIF2AK3 Leading to Wolcott-Rallison Syndrome. ( 24032041 )
2013
23
Wolcott-Rallison syndrome. ( 23263430 )
2012
24
Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. ( 22672868 )
2012
25
A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child. ( 21648287 )
2011
26
Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. ( 21518408 )
2011
27
Wolcott-Rallison syndrome. ( 21050479 )
2010
28
Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. ( 20202148 )
2010
29
Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. ( 19837917 )
2009
30
Recurrent acute liver failure and mitochondriopathy in a case of Wolcott-Rallison syndrome. ( 18704764 )
2008
31
A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome. ( 16813601 )
2006
32
Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. ( 15384883 )
2004
33
Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. ( 15220213 )
2004
34
Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. ( 12086964 )
2002
35
EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. ( 10932183 )
2000
36
Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome. ( 9598721 )
1998

Variations for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

UniProtKB/Swiss-Prot genetic disease variations for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

75
# Symbol AA change Variation ID SNP ID
1 EIF2AK3 p.Arg588Gln VAR_011408 rs121908569

ClinVar genetic disease variations for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

6
(show top 50) (show all 101)
# Gene Variation Type Significance SNP ID Assembly Location
1 EIF2AK3 NM_004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs) duplication Pathogenic rs869025178 GRCh37 Chromosome 2, 88890091: 88890091
2 EIF2AK3 NM_004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs) duplication Pathogenic rs869025178 GRCh38 Chromosome 2, 88590573: 88590573
3 EIF2AK3 NM_004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln) single nucleotide variant Pathogenic rs121908569 GRCh37 Chromosome 2, 88882948: 88882948
4 EIF2AK3 NM_004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln) single nucleotide variant Pathogenic rs121908569 GRCh38 Chromosome 2, 88583430: 88583430
5 EIF2AK3 NM_004836.6(EIF2AK3): c.2985+1G> A single nucleotide variant Pathogenic rs869025179 GRCh37 Chromosome 2, 88870391: 88870391
6 EIF2AK3 NM_004836.6(EIF2AK3): c.2985+1G> A single nucleotide variant Pathogenic rs869025179 GRCh38 Chromosome 2, 88570873: 88570873
7 EIF2AK3 EIF2AK3, 4-BP DEL, 1563GAAA deletion Pathogenic
8 EIF2AK3 NM_004836.6(EIF2AK3): c.994G> T (p.Glu332Ter) single nucleotide variant Pathogenic rs121908570 GRCh37 Chromosome 2, 88890344: 88890344
9 EIF2AK3 NM_004836.6(EIF2AK3): c.994G> T (p.Glu332Ter) single nucleotide variant Pathogenic rs121908570 GRCh38 Chromosome 2, 88590826: 88590826
10 EIF2AK3 NM_004836.6(EIF2AK3): c.61_63delCTG (p.Leu21del) deletion Benign rs72416210 GRCh37 Chromosome 2, 88926730: 88926732
11 EIF2AK3 NM_004836.6(EIF2AK3): c.61_63delCTG (p.Leu21del) deletion Benign rs72416210 GRCh38 Chromosome 2, 88627212: 88627214
12 EIF2AK3 NM_004836.6(EIF2AK3): c.154G> A (p.Ala52Thr) single nucleotide variant Benign/Likely benign rs201593811 GRCh37 Chromosome 2, 88926639: 88926639
13 EIF2AK3 NM_004836.6(EIF2AK3): c.154G> A (p.Ala52Thr) single nucleotide variant Benign/Likely benign rs201593811 GRCh38 Chromosome 2, 88627121: 88627121
14 EIF2AK3 NM_004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter) single nucleotide variant Pathogenic rs864621972 GRCh37 Chromosome 2, 88888393: 88888393
15 EIF2AK3 NM_004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter) single nucleotide variant Pathogenic rs864621972 GRCh38 Chromosome 2, 88588875: 88588875
16 EIF2AK3 NM_004836.6(EIF2AK3): c.1564_1565delTG (p.Trp522Glufs) deletion Pathogenic rs797045558 GRCh37 Chromosome 2, 88885444: 88885445
17 EIF2AK3 NM_004836.6(EIF2AK3): c.1564_1565delTG (p.Trp522Glufs) deletion Pathogenic rs797045558 GRCh38 Chromosome 2, 88585926: 88585927
18 EIF2AK3 NM_004836.6(EIF2AK3): c.*870_*875delATGTTT deletion Uncertain significance rs565147927 GRCh38 Chromosome 2, 88556861: 88556866
19 EIF2AK3 NM_004836.6(EIF2AK3): c.*870_*875delATGTTT deletion Uncertain significance rs565147927 GRCh37 Chromosome 2, 88856379: 88856384
20 EIF2AK3 NM_004836.6(EIF2AK3): c.*360C> T single nucleotide variant Uncertain significance rs551581209 GRCh38 Chromosome 2, 88557376: 88557376
21 EIF2AK3 NM_004836.6(EIF2AK3): c.*360C> T single nucleotide variant Uncertain significance rs551581209 GRCh37 Chromosome 2, 88856894: 88856894
22 EIF2AK3 NM_004836.6(EIF2AK3): c.*310_*311dupTA duplication Uncertain significance rs767645334 GRCh38 Chromosome 2, 88557425: 88557426
23 EIF2AK3 NM_004836.6(EIF2AK3): c.*310_*311dupTA duplication Uncertain significance rs767645334 GRCh37 Chromosome 2, 88856943: 88856944
24 EIF2AK3 NM_004836.6(EIF2AK3): c.2532T> C (p.Ser844=) single nucleotide variant Uncertain significance rs56094918 GRCh38 Chromosome 2, 88574951: 88574951
25 EIF2AK3 NM_004836.6(EIF2AK3): c.2532T> C (p.Ser844=) single nucleotide variant Uncertain significance rs56094918 GRCh37 Chromosome 2, 88874469: 88874469
26 EIF2AK3 NM_004836.6(EIF2AK3): c.2500G> A (p.Ala834Thr) single nucleotide variant Uncertain significance rs751296708 GRCh38 Chromosome 2, 88574983: 88574983
27 EIF2AK3 NM_004836.6(EIF2AK3): c.2500G> A (p.Ala834Thr) single nucleotide variant Uncertain significance rs751296708 GRCh37 Chromosome 2, 88874501: 88874501
28 EIF2AK3 NM_004836.6(EIF2AK3): c.2237T> C (p.Met746Thr) single nucleotide variant Uncertain significance rs201662849 GRCh37 Chromosome 2, 88874764: 88874764
29 EIF2AK3 NM_004836.6(EIF2AK3): c.2237T> C (p.Met746Thr) single nucleotide variant Uncertain significance rs201662849 GRCh38 Chromosome 2, 88575246: 88575246
30 EIF2AK3 NM_004836.6(EIF2AK3): c.2093G> A (p.Arg698His) single nucleotide variant Uncertain significance rs780592115 GRCh37 Chromosome 2, 88874908: 88874908
31 EIF2AK3 NM_004836.6(EIF2AK3): c.2093G> A (p.Arg698His) single nucleotide variant Uncertain significance rs780592115 GRCh38 Chromosome 2, 88575390: 88575390
32 EIF2AK3 NM_004836.6(EIF2AK3): c.1165+10T> C single nucleotide variant Uncertain significance rs745614562 GRCh37 Chromosome 2, 88889951: 88889951
33 EIF2AK3 NM_004836.6(EIF2AK3): c.1165+10T> C single nucleotide variant Uncertain significance rs745614562 GRCh38 Chromosome 2, 88590433: 88590433
34 EIF2AK3 NM_004836.6(EIF2AK3): c.-195G> T single nucleotide variant Uncertain significance rs886056421 GRCh37 Chromosome 2, 88926987: 88926987
35 EIF2AK3 NM_004836.6(EIF2AK3): c.-195G> T single nucleotide variant Uncertain significance rs886056421 GRCh38 Chromosome 2, 88627469: 88627469
36 EIF2AK3 NM_004836.6(EIF2AK3): c.*459G> T single nucleotide variant Uncertain significance rs886056412 GRCh38 Chromosome 2, 88557277: 88557277
37 EIF2AK3 NM_004836.6(EIF2AK3): c.*459G> T single nucleotide variant Uncertain significance rs886056412 GRCh37 Chromosome 2, 88856795: 88856795
38 EIF2AK3 NM_004836.6(EIF2AK3): c.*271T> G single nucleotide variant Uncertain significance rs886056414 GRCh38 Chromosome 2, 88557465: 88557465
39 EIF2AK3 NM_004836.6(EIF2AK3): c.*271T> G single nucleotide variant Uncertain significance rs886056414 GRCh37 Chromosome 2, 88856983: 88856983
40 EIF2AK3 NM_004836.6(EIF2AK3): c.*175A> T single nucleotide variant Uncertain significance rs886056415 GRCh38 Chromosome 2, 88557561: 88557561
41 EIF2AK3 NM_004836.6(EIF2AK3): c.*175A> T single nucleotide variant Uncertain significance rs886056415 GRCh37 Chromosome 2, 88857079: 88857079
42 EIF2AK3 NM_004836.6(EIF2AK3): c.3291A> G (p.Ser1097=) single nucleotide variant Uncertain significance rs10208681 GRCh38 Chromosome 2, 88557796: 88557796
43 EIF2AK3 NM_004836.6(EIF2AK3): c.3291A> G (p.Ser1097=) single nucleotide variant Uncertain significance rs10208681 GRCh37 Chromosome 2, 88857314: 88857314
44 EIF2AK3 NM_004836.6(EIF2AK3): c.1719T> C (p.Asn573=) single nucleotide variant Uncertain significance rs137927384 GRCh37 Chromosome 2, 88882992: 88882992
45 EIF2AK3 NM_004836.6(EIF2AK3): c.1719T> C (p.Asn573=) single nucleotide variant Uncertain significance rs137927384 GRCh38 Chromosome 2, 88583474: 88583474
46 EIF2AK3 NM_004836.6(EIF2AK3): c.1697A> T (p.Asp566Val) single nucleotide variant Uncertain significance rs55791823 GRCh37 Chromosome 2, 88883014: 88883014
47 EIF2AK3 NM_004836.6(EIF2AK3): c.1697A> T (p.Asp566Val) single nucleotide variant Uncertain significance rs55791823 GRCh38 Chromosome 2, 88583496: 88583496
48 EIF2AK3 NM_004836.6(EIF2AK3): c.1307-4T> G single nucleotide variant Uncertain significance rs548802949 GRCh37 Chromosome 2, 88887626: 88887626
49 EIF2AK3 NM_004836.6(EIF2AK3): c.1307-4T> G single nucleotide variant Uncertain significance rs548802949 GRCh38 Chromosome 2, 88588108: 88588108
50 EIF2AK3 NM_004836.6(EIF2AK3): c.719G> A (p.Arg240His) single nucleotide variant Uncertain significance rs147458427 GRCh37 Chromosome 2, 88892838: 88892838

Expression for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Search GEO for disease gene expression data for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus.

Pathways for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Pathways related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to KEGG:

37
# Name Kegg Source Accession
1 Protein processing in endoplasmic reticulum hsa04141

GO Terms for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Cellular components related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.26 EIF2AK3 IER3IP1 KCNJ11 PPP1R15B
2 sarcolemma GO:0042383 9.16 ABCC8 KCNJ11
3 inward rectifying potassium channel GO:0008282 8.62 ABCC8 KCNJ11

Biological processes related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of translation GO:0006417 9.37 EIF2AK3 PPP1R15B
2 potassium ion transport GO:0006813 9.32 ABCC8 KCNJ11
3 potassium ion transmembrane transport GO:0071805 9.26 ABCC8 KCNJ11
4 response to endoplasmic reticulum stress GO:0034976 9.16 EIF2AK3 PPP1R15B
5 regulation of insulin secretion GO:0050796 8.96 ABCC8 KCNJ11
6 ER overload response GO:0006983 8.62 EIF2AK3 PPP1R15B

Molecular functions related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.26 ABCC8 ALPK3 EIF2AK3 KCNJ11
2 ion channel binding GO:0044325 9.16 ABCC8 KCNJ11
3 ATP-activated inward rectifier potassium channel activity GO:0015272 8.62 ABCC8 KCNJ11

Sources for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

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17 ExPASy
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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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