ARCI4A
MCID: ICH040
MIFTS: 41

Ichthyosis, Congenital, Autosomal Recessive 4a (ARCI4A)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Ichthyosis, Congenital, Autosomal Recessive 4a

MalaCards integrated aliases for Ichthyosis, Congenital, Autosomal Recessive 4a:

Name: Ichthyosis, Congenital, Autosomal Recessive 4a 57 73 13
Autosomal Recessive Congenital Ichthyosis 4a 12 29 6 15
Ichthyosis Congenita Iib 57 12 20 73
Icr2b 57 12 20 73
Arci4a 57 12 73
Lamellar Ichthyosis 2 12 73
Li2 20 73
Ichthyosis, Congenital, Autosomal Recessive, Type 4a 39
Ichthyosis, Lamellar, 2, Formerly; Li2, Formerly 57
Ichthyosis, Lamellar, 2, Formerly 57
Ichthyosis Congenita Iib; Icr2b 57
Lamellar Ichthyosis, Type 2 20
Ichthyosis Lamellar 2 20
Li2, Formerly 57

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive


HPO:

31
ichthyosis, congenital, autosomal recessive 4a:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0060712
OMIM® 57 601277
OMIM Phenotypic Series 57 PS242300
MeSH 44 D017490
ICD10 32 Q80.2
MedGen 41 C1832550

Summaries for Ichthyosis, Congenital, Autosomal Recessive 4a

OMIM® : 57 Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300). (601277) (Updated 05-Mar-2021)

MalaCards based summary : Ichthyosis, Congenital, Autosomal Recessive 4a, also known as autosomal recessive congenital ichthyosis 4a, is related to ichthyosis and autosomal recessive congenital ichthyosis. An important gene associated with Ichthyosis, Congenital, Autosomal Recessive 4a is ABCA12 (ATP Binding Cassette Subfamily A Member 12), and among its related pathways/superpathways are Keratinization and Fat digestion and absorption. Affiliated tissues include Epidermis, and related phenotypes are leukonychia and clubbing

Disease Ontology : 12 An autosomal recessive congenital ichthyosis characterized by generalized ichthyosis and ectropion that has material basis in homozygous or compound hetrezogyous mutation in the ABCA12 gene on chromosome 2q35.

UniProtKB/Swiss-Prot : 73 Ichthyosis, congenital, autosomal recessive 4A: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.

Related Diseases for Ichthyosis, Congenital, Autosomal Recessive 4a

Diseases in the Ichthyosis family:

Ichthyosis, Congenital, Autosomal Recessive 2 Ichthyosis, Congenital, Autosomal Recessive 1
Ichthyosis, Congenital, Autosomal Recessive 4b Ichthyosis, Congenital, Autosomal Recessive 4a
Ichthyosis, Congenital, Autosomal Recessive 11 Ichthyosis, Congenital, Autosomal Recessive 5
Ichthyosis, Congenital, Autosomal Recessive 3 Ichthyosis, Congenital, Autosomal Recessive 6
Ichthyosis, Congenital, Autosomal Recessive 8 Ichthyosis, Congenital, Autosomal Recessive 7
Ichthyosis, Congenital, Autosomal Recessive 9 Ichthyosis, Congenital, Autosomal Recessive 10
Ichthyosis, Congenital, Autosomal Recessive 12 Ichthyosis, Congenital, Autosomal Recessive 14
Ichthyosis, Congenital, Autosomal Recessive 13 Autosomal Recessive Congenital Ichthyosis
Ichthyosis, Acquired Inherited Ichthyosis
Autosomal Ichthyosis Syndrome

Diseases related to Ichthyosis, Congenital, Autosomal Recessive 4a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 34)
# Related Disease Score Top Affiliating Genes
1 ichthyosis 29.7 TGM1 LORICRIN GBA ABCA12
2 autosomal recessive congenital ichthyosis 29.6 TGM1 LORICRIN ABCA12 ABCA1
3 rapidly involuting congenital hemangioma 10.2
4 ichthyosis, congenital, autosomal recessive 7 10.2 TGM1 ABCA12
5 x-linked chondrodysplasia punctata 2 10.2 TGM1 ABCA12
6 acrokeratosis verruciformis 10.2 TGM1 ABCA12
7 ichthyosis, congenital, autosomal recessive 1 10.2 TGM1 ABCA12
8 ectropion 10.1 TGM1 ABCA12
9 eyelid disease 10.1 TGM1 ABCA12
10 vohwinkel syndrome 10.1 TGM1 LORICRIN
11 skin papilloma 10.0 LORICRIN KRT14
12 netherton syndrome 10.0 TGM1 GBA
13 ichthyosis, x-linked 10.0 TGM1 ABCA12
14 ichthyosis, congenital, autosomal recessive 4b 10.0 TGM1 LORICRIN ABCA12
15 erythrokeratodermia variabilis et progressiva 1 10.0 TGM1 LORICRIN ABCA12
16 adermatoglyphia 10.0 LORICRIN KRT14
17 hyaline fibromatosis syndrome 10.0 LORICRIN KRT14
18 splenomegaly 9.9 GBA ABCA1
19 pachyonychia congenita 1 9.9 LORICRIN KRT14
20 epidermolytic hyperkeratosis 9.9 TGM1 LORICRIN KRT14
21 asymmetric motor neuropathy 9.8 H3-2 APOA1
22 hypoalphalipoproteinemia, primary, 1 9.8 APOA1 ABCA1
23 hypoalphalipoproteinemia 9.8 APOA1 ABCA1
24 hypoalphalipoproteinemia, primary, 2 9.8 APOA1 ABCA1
25 huntington disease-like 1 9.7 APOA1 ABCA1
26 ichthyosis vulgaris 9.7 TGM1 LORICRIN KRT14 ABCA12
27 keratosis 9.7 TGM1 LORICRIN KRT14 ABCA12
28 hair disease 9.7 LORICRIN KRT14
29 skin disease 9.7 TGM1 LORICRIN KRT14 ABCA12
30 sitosterolemia 9.6 APOA1 ABCA1
31 hypolipoproteinemia 9.6 APOA1 ABCA12 ABCA1
32 tangier disease 9.6 APOA1 ABCA12 ABCA1
33 homozygous familial hypercholesterolemia 9.5 APOA1 ABCA1
34 inherited metabolic disorder 9.3 H3-2 GBA APOA1 ABCA1

Graphical network of the top 20 diseases related to Ichthyosis, Congenital, Autosomal Recessive 4a:



Diseases related to Ichthyosis, Congenital, Autosomal Recessive 4a

Symptoms & Phenotypes for Ichthyosis, Congenital, Autosomal Recessive 4a

Human phenotypes related to Ichthyosis, Congenital, Autosomal Recessive 4a:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 leukonychia 31 occasional (7.5%) HP:0001820
2 clubbing 31 occasional (7.5%) HP:0001217
3 palmoplantar keratoderma 31 HP:0000982
4 abnormality of the nervous system 31 HP:0000707
5 ectropion 31 HP:0000656
6 congenital ichthyosiform erythroderma 31 HP:0007431
7 abnormal abdomen morphology 31 HP:0001438

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skin Nails Hair Skin:
palmoplantar keratoderma
collodion membrane at birth
ichthyosis, generalized, with involvement of flexural folds
large adherent dark pigmented scales
fine whitish scales (rare)

Skin Nails Hair Nails:
clubbing (rare)
leukonychia (rare)

Head And Neck Eyes:
ectropion

Clinical features from OMIM®:

601277 (Updated 05-Mar-2021)

Drugs & Therapeutics for Ichthyosis, Congenital, Autosomal Recessive 4a

Search Clinical Trials , NIH Clinical Center for Ichthyosis, Congenital, Autosomal Recessive 4a

Genetic Tests for Ichthyosis, Congenital, Autosomal Recessive 4a

Genetic tests related to Ichthyosis, Congenital, Autosomal Recessive 4a:

# Genetic test Affiliating Genes
1 Autosomal Recessive Congenital Ichthyosis 4a 29 ABCA12

Anatomical Context for Ichthyosis, Congenital, Autosomal Recessive 4a

MalaCards organs/tissues related to Ichthyosis, Congenital, Autosomal Recessive 4a:

40
Skin
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Ichthyosis, Congenital, Autosomal Recessive 4a:
# Tissue Anatomical CompartmentCell Relevance
1 Epidermis Stratified Epidermis Corneocytes Affected by disease
2 Epidermis Stratified Epidermis Granular Keratinocytes Affected by disease
3 Epidermis Stratified Epidermis Spinous Keratinocytes Affected by disease

Publications for Ichthyosis, Congenital, Autosomal Recessive 4a

Articles related to Ichthyosis, Congenital, Autosomal Recessive 4a:

# Title Authors PMID Year
1
Lamellar ichthyosis: further narrowing, physical and expression mapping of the chromosome 2 candidate locus. 61 6 57
10094194 1999
2
Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. 57 6
12915478 2003
3
Mapping of a second locus for lamellar ichthyosis to chromosome 2q33-35. 6 57
8845852 1996
4
ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts. 57
20672373 2010
5
Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. 57
20643494 2010
6
Autosomal recessive congenital ichthyosis. 57
19434086 2009
7
Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. 57
16436457 2006
8
Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis. 57
16116617 2005
9
The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis. 57
12780701 2003
10
Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. 57
10712205 2000

Variations for Ichthyosis, Congenital, Autosomal Recessive 4a

ClinVar genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 4a:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ABCA12 NM_173076.3(ABCA12):c.4142G>A (p.Gly1381Glu) SNV Pathogenic 2854 rs28940268 2:215851287-215851287 2:214986563-214986563
2 ABCA12 NM_173076.3(ABCA12):c.4139A>G (p.Asn1380Ser) SNV Pathogenic 2855 rs28940269 2:215851290-215851290 2:214986566-214986566
3 ABCA12 NM_173076.3(ABCA12):c.4951G>A (p.Gly1651Ser) SNV Pathogenic 2856 rs28940568 2:215843554-215843554 2:214978830-214978830
4 ABCA12 NM_173076.3(ABCA12):c.4541G>A (p.Arg1514His) SNV Pathogenic 2857 rs28940270 2:215846949-215846949 2:214982225-214982225
5 ABCA12 NM_173076.3(ABCA12):c.4615G>A (p.Glu1539Lys) SNV Pathogenic 2858 rs28940271 2:215845332-215845332 2:214980608-214980608
6 ABCA12 NM_173076.3(ABCA12):c.1657+1G>T SNV Likely pathogenic 560161 rs758568142 2:215884059-215884059 2:215019335-215019335
7 ABCA12 NM_173076.3(ABCA12):c.859C>T (p.Arg287Ter) SNV Likely pathogenic 264999 rs11891778 2:215910574-215910574 2:215045850-215045850
8 ABCA12 NM_173076.3(ABCA12):c.4139A>G (p.Asn1380Ser) SNV Likely pathogenic 2855 rs28940269 2:215851290-215851290 2:214986566-214986566

UniProtKB/Swiss-Prot genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 4a:

73 (show all 12)
# Symbol AA change Variation ID SNP ID
1 ABCA12 p.Asn1380Ser VAR_019598 rs28940269
2 ABCA12 p.Gly1381Glu VAR_019599 rs28940268
3 ABCA12 p.Arg1514His VAR_019600 rs28940270
4 ABCA12 p.Glu1539Lys VAR_019601 rs28940271
5 ABCA12 p.Gly1651Ser VAR_019602 rs28940568
6 ABCA12 p.Thr345Pro VAR_067075 rs129593586
7 ABCA12 p.Gly1136Asp VAR_067077
8 ABCA12 p.Trp1235Ser VAR_067079
9 ABCA12 p.Ile1494Thr VAR_067080 rs126369859
10 ABCA12 p.Gly1559Val VAR_067081 rs145751315
11 ABCA12 p.Pro1798Leu VAR_067082 rs181314573
12 ABCA12 p.Thr1980Lys VAR_067083 rs763858530

Expression for Ichthyosis, Congenital, Autosomal Recessive 4a

Search GEO for disease gene expression data for Ichthyosis, Congenital, Autosomal Recessive 4a.

Pathways for Ichthyosis, Congenital, Autosomal Recessive 4a

Pathways related to Ichthyosis, Congenital, Autosomal Recessive 4a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.59 TGM1 LORICRIN KRT14
2
Show member pathways
10.82 APOA1 ABCA1
3 9.9 APOA1 ABCA1

GO Terms for Ichthyosis, Congenital, Autosomal Recessive 4a

Cellular components related to Ichthyosis, Congenital, Autosomal Recessive 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endocytic vesicle GO:0030139 8.96 APOA1 ABCA1
2 cornified envelope GO:0001533 8.62 TGM1 LORICRIN

Biological processes related to Ichthyosis, Congenital, Autosomal Recessive 4a according to GeneCards Suite gene sharing:

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 lipid transport GO:0006869 9.67 APOA1 ABCA12 ABCA1
2 steroid metabolic process GO:0008202 9.65 GBA APOA1 ABCA1
3 response to estrogen GO:0043627 9.61 GBA APOA1
4 cornification GO:0070268 9.61 TGM1 LORICRIN KRT14
5 intermembrane lipid transfer GO:0120009 9.6 APOA1 ABCA1
6 lysosome organization GO:0007040 9.59 GBA ABCA1
7 phospholipid transport GO:0015914 9.58 APOA1 ABCA1
8 peptide cross-linking GO:0018149 9.58 TGM1 LORICRIN
9 cholesterol metabolic process GO:0008203 9.58 GBA APOA1 ABCA1
10 cholesterol efflux GO:0033344 9.57 APOA1 ABCA1
11 lipid storage GO:0019915 9.56 GBA APOA1
12 lipoprotein metabolic process GO:0042157 9.55 APOA1 ABCA1
13 cholesterol transport GO:0030301 9.54 APOA1 ABCA1
14 reverse cholesterol transport GO:0043691 9.52 APOA1 ABCA1
15 phospholipid homeostasis GO:0055091 9.51 APOA1 ABCA1
16 high-density lipoprotein particle assembly GO:0034380 9.46 APOA1 ABCA1
17 keratinization GO:0031424 9.46 TGM1 LORICRIN KRT14 ABCA12
18 keratinocyte differentiation GO:0030216 9.43 TGM1 LORICRIN ABCA12
19 regulation of Cdc42 protein signal transduction GO:0032489 9.37 APOA1 ABCA1
20 lipoprotein biosynthetic process GO:0042158 9.32 APOA1 ABCA1
21 positive regulation of cholesterol efflux GO:0010875 9.13 APOA1 ABCA12 ABCA1
22 phospholipid efflux GO:0033700 8.8 APOA1 ABCA12 ABCA1

Molecular functions related to Ichthyosis, Congenital, Autosomal Recessive 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 9.46 GBA APOA1 ABCA12 ABCA1
2 ATPase activity, coupled to transmembrane movement of substances GO:0042626 9.43 ABCA12 ABCA1
3 cholesterol binding GO:0015485 9.4 APOA1 ABCA1
4 phosphatidylcholine binding GO:0031210 9.37 APOA1 ABCA1
5 intermembrane cholesterol transfer activity GO:0120020 9.32 APOA1 ABCA1
6 high-density lipoprotein particle binding GO:0008035 9.26 APOA1 ABCA1
7 apolipoprotein A-I receptor binding GO:0034191 8.96 APOA1 ABCA12
8 lipid transporter activity GO:0005319 8.8 APOA1 ABCA12 ABCA1

Sources for Ichthyosis, Congenital, Autosomal Recessive 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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