ABCA12

ATP binding cassette subfamily A member 12, the group of ATP binding cassette subfamily A

Basic information

Region (hg38): 2:214931542-215138626

Previous symbols: [ "ICR2B" ]

Links

ENSG00000144452 ∙ NCBI:26154 ∙ OMIM:607800 ∙ HGNC:14637 ∙ Uniprot:Q86UK0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive congenital ichthyosis 4B (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 4A (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 4A (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 4B (Strong), mode of inheritance: AR
• lamellar ichthyosis (Supportive), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 4B (Supportive), mode of inheritance: AR
• congenital non-bullous ichthyosiform erythroderma (Supportive), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 4A (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 4A; Ichthyosis, congenital, autosomal recessive 4B	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	8204475; 12208260; 12915478; 16007253; 15756637; 16902423; 21339420; 21729033; 22257947

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCA12 gene.

• not provided (76 variants)
• Autosomal recessive congenital ichthyosis 4B (8 variants)
• Autosomal recessive congenital ichthyosis 4A (4 variants)
• Lamellar ichthyosis (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCA12 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	466	32	504
missense	2	18	181	97	26	324
nonsense	35	5	1			41
start loss						0
frameshift	37	7	1			45
inframe indel			1			1
splice donor/acceptor (+/-2bp)	5	30	1			36
splice region		1	7	72	3	83
non coding			20	250	49	319
Total	79	60	211	813	107

Highest pathogenic variant AF is 0.0000394

Variants in ABCA12

This is a list of pathogenic ClinVar variants found in the ABCA12 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-214931578-G-GACAA		Congenital ichthyosiform erythroderma	Benign (Jun 14, 2016)
2-214931726-C-G		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214931753-A-G		Congenital ichthyosis of skin	Benign (Jan 13, 2018)
2-214931790-G-A		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214931824-T-C		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214931844-T-C		Congenital ichthyosis of skin	Benign (Jan 12, 2018)
2-214931902-C-T		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214931910-C-T		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214931914-C-G		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214931921-A-C		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214931970-G-C		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214932060-G-A		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214932082-C-T		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214932094-A-AC		Congenital ichthyosiform erythroderma	Likely benign (Jun 14, 2016)
2-214932109-A-ACAT		Congenital ichthyosiform erythroderma	Uncertain significance (Jun 14, 2016)
2-214932149-A-G		Congenital ichthyosis of skin	Benign (Jan 12, 2018)
2-214932169-C-T		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214932238-G-A		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214932256-C-G		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214932256-C-T		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214932269-C-G		Congenital ichthyosis of skin	Uncertain significance (Feb 09, 2018)
2-214932290-A-G		Congenital ichthyosis of skin	Uncertain significance (Jan 13, 2018)
2-214932324-T-C		Congenital ichthyosis of skin	Benign (Jan 13, 2018)
2-214932359-G-T		Congenital ichthyosis of skin	Uncertain significance (Jan 12, 2018)
2-214932608-C-T		Congenital ichthyosis of skin • Autosomal recessive congenital ichthyosis 4A • Autosomal recessive congenital ichthyosis 4B	Benign (Jul 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCA12	protein_coding	protein_coding	ENST00000272895	53	206886

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.92e-15	1.00	125579	0	169	125748	0.000672

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.63	1175	1.34e+3	0.875	0.0000694	17089
Missense in Polyphen		404	504.5	0.80079		6448
Synonymous	-0.564	519	503	1.03	0.0000277	4958
Loss of Function	6.64	50	133	0.377	0.00000725	1605

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00113
Ashkenazi Jewish	0.000596	0.000595
East Asian	0.000763	0.000761
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000576	0.000571
Middle Eastern	0.000763	0.000761
South Asian	0.00230	0.00141
Other	0.00140	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transporter involved in lipid homeostasis.
• Disease: DISEASE: Ichthyosis, congenital, autosomal recessive 4A (ARCI4A) [MIM:601277]: 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. {ECO:0000269|PubMed:12915478, ECO:0000269|PubMed:17508018, ECO:0000269|PubMed:18284401, ECO:0000269|PubMed:19262603, ECO:0000269|PubMed:22257947}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ichthyosis, congenital, autosomal recessive 4B (ARCI4B) [MIM:242500]: A rare, very severe form of congenital ichthyosis, in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period. Babies who survive into infancy and beyond develop skin changes resembling severe non-bullous congenital ichthyosiform erythroderma. {ECO:0000269|PubMed:16675967, ECO:0000269|PubMed:16902423}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ABC transporters - Homo sapiens (human);ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.0151
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.27

Haploinsufficiency Scores

• pHI: 0.163
• hipred: N
• hipred_score: 0.466
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.138

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Abca12
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: abca12
• Affected structure: keratinocyte
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: lipid transport;positive regulation of cholesterol efflux;cellular homeostasis;keratinization;secretion by cell;phospholipid efflux;ceramide transport;surfactant homeostasis;regulated exocytosis;lung alveolus development;transmembrane transport;lipid homeostasis;establishment of skin barrier;protein localization to plasma membrane;positive regulation of protein localization to cell surface
• Cellular component: cytoplasm;cytosol;plasma membrane;integral component of membrane;intracellular membrane-bounded organelle;epidermal lamellar body
• Molecular function: signaling receptor binding;lipid transporter activity;protein binding;ATP binding;lipid-transporting ATPase activity;apolipoprotein A-I receptor binding;ATPase activity, coupled to transmembrane movement of substances