Cutis Laxa, Autosomal Recessive, Type Iid disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

OMIM®: ⁵⁷ Autosomal recessive cutis laxa type IID (ARCL2D) is characterized by generalized skin wrinkling with sparse subcutaneous fat and dysmorphic progeroid facial features. Most patients also exhibit severe hypotonia as well as cardiovascular and neurologic involvement (summary by Van Damme et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). (617403) (Updated 08-Dec-2022)

MalaCards based summary: Cutis Laxa, Autosomal Recessive, Type Iid, also known as arcl2d, is related to cutis laxa, autosomal recessive, type ia and cutis laxa, autosomal dominant 1. An important gene associated with Cutis Laxa, Autosomal Recessive, Type Iid is ATP6V1A (ATPase H+ Transporting V1 Subunit A), and among its related pathways/superpathways are Signaling by Receptor Tyrosine Kinases and Insulin receptor signalling cascade. Affiliated tissues include skin, cortex and heart, and related phenotypes are seizure and failure to thrive

UniProtKB/Swiss-Prot: ⁷³ A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. Most ARCL2D patients exhibit severe hypotonia as well as cardiovascular and neurologic involvement.

Disease Ontology: ¹¹ An autosomal recessive cutis laxa type II classic type that is characterized by generalized skin wrinkling with sparse subcutaneous fat and dysmorphic progeroid facial featuret and that has material basis in homozygous mutation in the ATP6V1A gene on chromosome 3q13.

Sources

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iid

Diseases in the Cutis Laxa family:

Cutis Laxa, Autosomal Dominant 1	Cutis Laxa, Autosomal Recessive, Type Ia
Cutis Laxa, Autosomal Recessive, Type Iiia	Cutis Laxa, Autosomal Recessive, Type Iia
Cutis Laxa, Autosomal Recessive, Type Iib	Cutis Laxa, Autosomal Recessive, Type Ic
Cutis Laxa, Autosomal Dominant 2	Cutis Laxa, Autosomal Recessive, Type Ib
Cutis Laxa, Autosomal Recessive, Type Iiib	Cutis Laxa, Autosomal Dominant 3
Cutis Laxa, Autosomal Recessive, Type Iic	Cutis Laxa, Autosomal Recessive, Type Iid
Cutis Laxa, Autosomal Recessive, Type Iie	Autosomal Recessive Cutis Laxa Type Iii
Autosomal Recessive Cutis Laxa Type I	Atp6v0a2-Related Cutis Laxa
Efemp2-Related Cutis Laxa	Eln-Related Cutis Laxa
Fbln5-Related Cutis Laxa	Ltbp4-Related Cutis Laxa
Acquired Cutis Laxa

Diseases related to Cutis Laxa, Autosomal Recessive, Type Iid via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)

#	Related Disease	Score	Top Affiliating Genes
1	cutis laxa, autosomal recessive, type ia	9.8	ATP6V0A2 ALDH18A1
2	cutis laxa, autosomal dominant 1	9.8	ATP6V0A2 ALDH18A1
3	congenital disorder of glycosylation, type in	9.6	GORAB ATP6V0A2
4	wrinkly skin syndrome	9.6	GORAB ATP6V0A2 ALDH18A1
5	cutis laxa, autosomal dominant 3	9.5	PI4K2A ATP6V1E1 ALDH18A1
6	immunodeficiency 47	9.5	ATP6V1E1 ATP6V1A ATP6V0A2 ALDH18A1
7	autosomal recessive cutis laxa type i	9.4	RIN2 GORAB ATP6V0A2 ALDH18A1
8	autosomal recessive cutis laxa type iii	9.4	RIN2 GORAB ATP6V0A2 ALDH18A1
9	cutis laxa, autosomal recessive, type iiib	9.4	RIN2 GORAB ATP6V0A2 ALDH18A1
10	cutis laxa, autosomal recessive, type iiia	9.4	RIN2 GORAB ATP6V0A2 ALDH18A1
11	cutis laxa, autosomal recessive, type ic	9.3	RIN2 GORAB ATP6V0A2 ALDH18A1
12	cutis laxa, autosomal recessive, type ib	9.3	RIN2 GORAB ATP6V0A2 ALDH18A1
13	occipital horn syndrome	9.3	RIN2 GORAB ATP6V0A2 ALDH18A1
14	cutis laxa, autosomal recessive, type iib	9.2	RIN2 GORAB ATP6V1E1 ATP6V0A2 ALDH18A1
15	cutis laxa, autosomal recessive, type iia	9.0	RIN2 GORAB ATP6V1E1 ATP6V1A ATP6V0A2 ALDH18A1
16	cutis laxa	9.0	RIN2 GORAB ATP6V1E1 ATP6V1A ATP6V0A2 ALDH18A1
17	geroderma osteodysplasticum	9.0	RIN2 GORAB ATP6V1E1 ATP6V1A ATP6V0A2 ALDH18A1
18	autosomal recessive cutis laxa type ii classic type	8.6	RIN2 PI4K2A GORAB ATP6V1E1 ATP6V1A ATP6V0A2

Graphical network of the top 20 diseases related to Cutis Laxa, Autosomal Recessive, Type Iid:

Sources

Symptoms & Phenotypes for Cutis Laxa, Autosomal Recessive, Type Iid

Human phenotypes related to Cutis Laxa, Autosomal Recessive, Type Iid:

³⁰ (show all 31)

#	Description	HPO Source Accession
1	seizure ³⁰	HP:0001250
2	failure to thrive ³⁰	HP:0001508
3	cataract ³⁰	HP:0000518
4	inguinal hernia ³⁰	HP:0000023
5	hypertelorism ³⁰	HP:0000316
6	macrotia ³⁰	HP:0000400
7	wide nasal bridge ³⁰	HP:0000431
8	delayed speech and language development ³⁰	HP:0000750
9	congestive heart failure ³⁰	HP:0001635
10	retrognathia ³⁰	HP:0000278
11	low-set ears ³⁰	HP:0000369
12	atrial septal defect ³⁰	HP:0001631
13	hypertrophic cardiomyopathy ³⁰	HP:0001639
14	mask-like facies ³⁰	HP:0000298
15	motor delay ³⁰	HP:0001270
16	talipes equinovarus ³⁰	HP:0001762
17	disproportionate tall stature ³⁰	HP:0001519
18	downslanted palpebral fissures ³⁰	HP:0000494
19	micropenis ³⁰	HP:0000054
20	protruding ear ³⁰	HP:0000411
21	hip dislocation ³⁰	HP:0002827
22	bulbous nose ³⁰	HP:0000414
23	blepharophimosis ³⁰	HP:0000581
24	triangular face ³⁰	HP:0000325
25	right bundle branch block ³⁰	HP:0011712
26	generalized hypotonia ³⁰	HP:0001290
27	hypoplasia of the corpus callosum ³⁰	HP:0002079
28	camptodactyly ³⁰	HP:0012385
29	entropion ³⁰	HP:0000621
30	bilateral cryptorchidism ³⁰	HP:0008689
31	gliosis ³⁰	HP:0002171

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 08-Dec-2022)

Growth Other:
failure to thrive
marfanoid habitus

Genitourinary External Genitalia Male:
inguinal hernia
micropenis

Head And Neck Ears:
low-set ears
large ears
prominent ears
simple folded helices

Head And Neck Face:
mask-like facies
triangular face
receding chin
short forehead
progeroid facies

Skeletal Hands:
camptodactyly

Skeletal Feet:
club feet

Genitourinary Internal Genitalia Male:
cryptorchidism, bilateral

Skin Nails Hair Skin Electron Microscopy:
reduced elastic fibers
fragmented elastic fibers
loosely packed collagen fibers
variable diameters of collagen fibers

Metabolic Features:
abnormal serum glycosylation

Neurologic Central Nervous System:
hypotonia
motor delay
thin corpus callosum
seizures
speech delay
more

Head And Neck Eyes:
hypertelorism
blepharophimosis
entropion
downslanting palpebral fissures
bilateral cataract

Cardiovascular Heart:
atrial septal defect
cardiac failure
cardiomyopathy, hypertrophic
dilated ascending aorta
tortuous aortic arch
more

Head And Neck Nose:
bulbous nose
broad nasal bridge

Skeletal Pelvis:
dislocated hips

Skin Nails Hair Skin:
generalized skin wrinkling

Muscle Soft Tissue:
abnormal fat distribution

Skeletal:
flexion contractures of all joints

Clinical features from OMIM®:

617403 (Updated 08-Dec-2022)

Sources

Drugs & Therapeutics for Cutis Laxa, Autosomal Recessive, Type Iid

Search Clinical Trials, NIH Clinical Center for Cutis Laxa, Autosomal Recessive, Type Iid

Sources

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iid

Genetic tests related to Cutis Laxa, Autosomal Recessive, Type Iid:

#	Genetic test	Affiliating Genes
1	Autosomal Recessive Cutis Laxa Type 2d ²⁸	ATP6V1A

Sources

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iid

Organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Iid:

MalaCards : Skin, Cortex, Heart

Sources

Publications for Cutis Laxa, Autosomal Recessive, Type Iid

Articles related to Cutis Laxa, Autosomal Recessive, Type Iid:

#	Title	Authors	PMID	Year
1	Mutations in ATP6V1E1 or ATP6V1A Cause Autosomal-Recessive Cutis Laxa. ⁵⁷ ⁵	Van Damme T...Wevers RA	28065471	2017
2	A novel phenotype associated with cutis laxa, abnormal fat distribution, cardiomyopathy and cataract. ⁵⁷ ⁵	Van Asbeck E...Morava E	24459010	2014
3	Expanding the clinical and molecular spectrum of ATP6V1A related metabolic cutis laxa. ⁶²	Vogt G...Fischer-Zirnsak B	33320377	2021

Sources

Genes for Cutis Laxa, Autosomal Recessive, Type Iid

Genes related to Cutis Laxa, Autosomal Recessive, Type Iid (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	ATP6V1A	ATPase H+ Transporting V1 Subunit A	Protein Coding	1307	Molecular basis known ⁵⁷ Pathogenic ⁵ Causative variation ⁷³ Genetic Tests ²⁸ DISEASES inferred ¹⁴	24459010 28065471
2	ATP6V1E1	ATPase H+ Transporting V1 Subunit E1	Protein Coding	6.99	DISEASES inferred ¹⁴
3	ATP6V0A2	ATPase H+ Transporting V0 Subunit A2	Protein Coding	6.34	DISEASES inferred ¹⁴
4	ALDH18A1	Aldehyde Dehydrogenase 18 Family Member A1	Protein Coding	6.19	DISEASES inferred ¹⁴
5	GORAB	Golgin, RAB6 Interacting	Protein Coding	6.08	DISEASES inferred ¹⁴
6	PI4K2A	Phosphatidylinositol 4-Kinase Type 2 Alpha	Protein Coding	6.06	DISEASES inferred ¹⁴
7	RIN2	Ras And Rab Interactor 2	Protein Coding	5.98	DISEASES inferred ¹⁴

Sources

Variations for Cutis Laxa, Autosomal Recessive, Type Iid

ClinVar genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Iid:

⁵

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	ATP6V1A	NM_001690.4(ATP6V1A):c.215G>A (p.Gly72Asp)	SNV	Pathogenic	417773	rs1060505037	GRCh37: 3:113503074-113503074 GRCh38: 3:113784227-113784227
2	ATP6V1A	NM_001690.4(ATP6V1A):c.1012C>T (p.Arg338Cys)	SNV	Pathogenic	417772	rs1060505036	GRCh37: 3:113513742-113513742 GRCh38: 3:113794895-113794895
3	ATP6V1A	NM_001690.4(ATP6V1A):c.1531G>C (p.Val511Leu)	SNV	Uncertain Significance	930734	rs1709239976	GRCh37: 3:113522466-113522466 GRCh38: 3:113803619-113803619
4	ATP6V1A	NM_001690.4(ATP6V1A):c.1227-6A>G	SNV	Uncertain Significance	931142	rs1709148623	GRCh37: 3:113514717-113514717 GRCh38: 3:113795870-113795870

UniProtKB/Swiss-Prot genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Iid:

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	ATP6V1A	p.Gly72Asp	VAR_078606	rs1060505037
2	ATP6V1A	p.Arg338Cys	VAR_078607	rs1060505036

Sources

Expression for Cutis Laxa, Autosomal Recessive, Type Iid

Search GEO for disease gene expression data for Cutis Laxa, Autosomal Recessive, Type Iid.

Sources

Pathways for Cutis Laxa, Autosomal Recessive, Type Iid

Pathways related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Signaling by Receptor Tyrosine Kinases ⁶⁶	12.22	ATP6V1E1 ATP6V1A ATP6V0A2
2	Insulin receptor signalling cascade ⁶⁶ Show member pathways Glucose homeostasis ⁷⁴ IGF1R signaling cascade ⁶⁶ IRS activation ⁶⁶ IRS-mediated signalling ⁶⁶ IRS-related events triggered by IGF1R ⁶⁶ PI3K Cascade ⁶⁶ SHC-related events triggered by IGF1R ⁶⁶ Signal attenuation ⁶⁶ Signaling by Insulin receptor ⁶⁶ Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) ⁶⁶ SOS-mediated signalling ⁶⁶	12.06	ATP6V1E1 ATP6V1A ATP6V0A2
3	Ion channel transport ⁶⁶ Show member pathways Stimuli-sensing channels ⁶⁶	11.6	ATP6V1E1 ATP6V1A ATP6V0A2
4	Insulin receptor recycling ⁶⁶ Show member pathways ATP biosynthesis ⁶¹ Events associated with phagocytolytic activity of PMN cells ⁶⁶ Iron uptake and transport ⁶⁶ melatonin degradation III ⁶¹ ROS and RNS production in phagocytes ⁶⁶ Transferrin endocytosis and recycling ⁶⁶	11.03	ATP6V1E1 ATP6V1A ATP6V0A2
5	Proximal tubule transport ⁷⁴	10.91	ATP6V1E1 ATP6V1A

Sources

GO Terms for Cutis Laxa, Autosomal Recessive, Type Iid

Cellular components related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	lysosomal membrane	GO:0005765	9.86	PI4K2A ATP6V1E1 ATP6V1A ATP6V0A2
2	microvillus	GO:0005902	9.73	ATP6V1E1 ATP6V1A
3	clathrin-coated vesicle membrane	GO:0030665	9.71	ATP6V1E1 ATP6V1A
4	proton-transporting V-type ATPase complex	GO:0033176	9.62	ATP6V1A ATP6V0A2
5	vacuolar proton-transporting V-type ATPase, V1 domain	GO:0000221	9.46	ATP6V1E1 ATP6V1A
6	ATPase complex	GO:1904949	9.37	ATP6V1A ATP6V0A2
7	transmembrane transporter complex	GO:1902495	8.96	ATP6V1A ATP6V0A2
8	proton-transporting two-sector ATPase complex	GO:0016469	8.92	ATP6V1E1 ATP6V1A

Biological processes related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	proton transmembrane transport	GO:1902600	9.8	ATP6V1E1 ATP6V1A ATP6V0A2
2	cellular iron ion homeostasis	GO:0006879	9.71	ATP6V1A ATP6V0A2
3	vacuolar acidification	GO:0007035	9.67	ATP6V1A ATP6V0A2
4	Golgi lumen acidification	GO:0061795	9.56	ATP6V1A ATP6V0A2
5	cellular response to increased oxygen levels	GO:0036295	9.26	ATP6V1A ATP6V0A2
6	synaptic vesicle lumen acidification	GO:0097401	9.16	ATP6V1E1 ATP6V1A
7	regulation of macroautophagy	GO:0016241	9.1	ATP6V1E1 ATP6V1A ATP6V0A2

Molecular functions related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	proton-transporting ATPase activity, rotational mechanism	GO:0046961	9.1	ATP6V1E1 ATP6V1A ATP6V0A2

Sources

Sources for Cutis Laxa, Autosomal Recessive, Type Iid

¹ BitterDB

² CDC

³ Cell Signaling Technology

⁴ ClinicalTrials

⁵ ClinVar

⁶ CNVD

⁷ Cochrane Library

⁸ Cosmic

⁹ dbSNP

¹⁰ DGIdb

¹¹ Disease Ontology

¹² diseasecard

¹³ DiseaseEnhancer

¹⁴ DISEASES

¹⁵ DrugBank

¹⁶ EFO

¹⁷ ExPASy

¹⁸ FMA

¹⁹ GARD

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ GenomeRNAi

²⁶ GEO DataSets

²⁷ GO

²⁸ GTR

²⁹ HMDB

³⁰ HPO

³¹ ICD10

³² ICD10 via Orphanet

³³ ICD11

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ LifeMap

³⁷ LncRNADisease

³⁸ LOVD

³⁹ MalaCards

⁴⁰ MedGen

⁴¹ MedlinePlus

⁴² MedlinePlus Genetics

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NINDS

⁵³ Novoseek

⁵⁴ Novus Biologicals

⁵⁵ ODiseA

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 08-Dec-2022)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubChem

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ WikiPathways

⁷⁵ Wikipedia

ARCL2D MCID: CTS043 MIFTS: 39	Cutis Laxa, Autosomal Recessive, Type Iid (ARCL2D) Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases	Data Licensing For inquiries, contact: [email protected]
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Expand all tables

Cutis Laxa, Autosomal Recessive, Type Iid (ARCL2D)

Aliases & Classifications for Cutis Laxa, Autosomal Recessive, Type Iid

MalaCards integrated aliases for Cutis Laxa, Autosomal Recessive, Type Iid:

Characteristics:

Inheritance:

OMIM®:

Classifications:

External Ids:

Summaries for Cutis Laxa, Autosomal Recessive, Type Iid

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iid

Diseases in the Cutis Laxa family:

Diseases related to Cutis Laxa, Autosomal Recessive, Type Iid via text searches within MalaCards or GeneCards Suite gene sharing:

Graphical network of the top 20 diseases related to Cutis Laxa, Autosomal Recessive, Type Iid:

Symptoms & Phenotypes for Cutis Laxa, Autosomal Recessive, Type Iid

Human phenotypes related to Cutis Laxa, Autosomal Recessive, Type Iid:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

Drugs & Therapeutics for Cutis Laxa, Autosomal Recessive, Type Iid

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iid

Genetic tests related to Cutis Laxa, Autosomal Recessive, Type Iid:

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iid

Organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Iid:

Publications for Cutis Laxa, Autosomal Recessive, Type Iid

Articles related to Cutis Laxa, Autosomal Recessive, Type Iid:

Genes for Cutis Laxa, Autosomal Recessive, Type Iid

Genes related to Cutis Laxa, Autosomal Recessive, Type Iid (1 elite genes):

Variations for Cutis Laxa, Autosomal Recessive, Type Iid

ClinVar genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Iid:

UniProtKB/Swiss-Prot genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Iid:

Expression for Cutis Laxa, Autosomal Recessive, Type Iid

Pathways for Cutis Laxa, Autosomal Recessive, Type Iid

Pathways related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

GO Terms for Cutis Laxa, Autosomal Recessive, Type Iid

Cellular components related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

Biological processes related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

Molecular functions related to Cutis Laxa, Autosomal Recessive, Type Iid according to GeneCards Suite gene sharing:

Sources for Cutis Laxa, Autosomal Recessive, Type Iid