ABCA12

protein-coding

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

Gene summary

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Previous symbols:

ICR2B

MANE transcript

NM_173076.3

Inheritance

ClinVar variants

P:223U:398B:742

Top phenotype

Ichthyosis, congenital, autosomal recessive 4A; Ichthyosis, congenital, autosomal recessive 4B

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr2:214,931,542-215,138,626

External References & Databases

Ensembl (ENSG00000144452)

Transcript & Mutation Effects

hg38 • Region Span ~207.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive congenital ichthyosis 4BSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009443

Submitter: Genomics England PanelApp

congenital non-bullous ichthyosiform erythrodermaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019306

Submitter: Orphanet

autosomal recessive congenital ichthyosis 4BSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009443

Submitter: Orphanet

autosomal recessive congenital ichthyosis 4ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011026

Submitter: Genomics England PanelApp

autosomal recessive congenital ichthyosis 4BDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009443

Submitter: G2P

autosomal recessive congenital ichthyosis 4ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011026

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive congenital ichthyosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0017265

Submitter: PanelApp Australia

lamellar ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017778

Submitter: Orphanet

Clinical Genomic Database (CGD)

Ichthyosis, congenital, autosomal recessive 4A; Ichthyosis, congenital, autosomal recessive 4BAR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 8204475; 12208260; 12915478; 16007253; 15756637; 16902423; 21339420; 21729033; 22257947

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCA12 variants in ClinVar

12 Conditions Cataloged

not providedTotal: 1345

Inborn genetic diseasesTotal: 350

Congenital ichthyosis of skinTotal: 127

Autosomal recessive congenital ichthyosis 4BTotal: 87

ABCA12-related disorderTotal: 74

Autosomal recessive congenital ichthyosis 4ATotal: 70

not specifiedTotal: 64

Lamellar ichthyosisTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173076.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		3 clinvar	12 clinvar	535 clinvar	28 clinvar	578
missense	6 clinvar	31 clinvar	380 clinvar	162 clinvar	17 clinvar	596
nonsense	39 clinvar	13 clinvar	3 clinvar			55
start loss	1 clinvar					1
frameshift	51 clinvar	26 clinvar				77
splice donor/acceptor (+/-2bp)	9 clinvar	44 clinvar	3 clinvar			56
Total	106	117	398	697	45	1363

Highest pathogenic variant AF is 0.00030388162

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173076.3	RefSeq	NP_775099.2	53	MANE Select
ENST00000272895.12	Ensembl	ENSP00000272895.7	53	MANE Select
NM_015657.4	RefSeq	NP_056472.2	45	Standard
ENST00000389661.4	Ensembl	ENSP00000374312.4	45	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
abca12	Danio rerio	Structure: keratinocyte Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

abca12

Danio rerio

Structure: keratinocyte

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

ABC transporters - Homo sapiens (human)
ABC transporters in lipid homeostasis
Transport of small molecules
ABC-family proteins mediated transport

Biological Process

lipid transport
positive regulation of cholesterol efflux
cellular homeostasis
keratinization
secretion by cell

Molecular Function

signaling receptor binding
lipid transporter activity
protein binding
ATP binding
lipid-transporting ATPase activity

Cellular Component

cytoplasm
cytosol
plasma membrane
integral component of membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000272895
Coding exons: 53
Length: 206886
Individuals with no LoFs: 125579
Homozygous LoFs: 0
Heterozygous LoFs: 169
Defined: 125748
p: 0.000672

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.63	1175	1.34e+3	0.875	0.0000694	17089
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00049	rare
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.00076	0.00076	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00058	0.00057	rare
South Asian	0.0023	0.0014	notable
Other	0.0014	0.0011	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.158

Intolerance Scores

LoFtool: 0.0151
RVIS EVS: -0.3
RVIS percentile EVS: 32.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.138

Gene Damage Prediction

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