ANTXR1

protein-coding

ANTXR cell adhesion molecule 1, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a type I transmembrane protein and is a tumor-specific endothelial marker that has been implicated in colorectal cancer. The encoded protein has been shown to also be a docking protein or receptor for Bacillus anthracis toxin, the causative agent of the disease, anthrax. The binding of the protective antigen (PA) component, of the tripartite anthrax toxin, to this receptor protein mediates delivery of toxin components to the cytosol of cells. Once inside the cell, the other two components of anthrax toxin, edema factor (EF) and lethal factor (LF) disrupt normal cellular processes. Three alternatively spliced variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

MANE transcript

NM_032208.3

Inheritance

AR, AD

ClinVar variants

P:11U:89B:33

Top phenotype

Hemangioma, capillary infantile, susceptibility to; Growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO syndrome)

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr2:69,013,176-69,249,327

External References & Databases

Ensembl (ENSG00000169604)

Transcript & Mutation Effects

hg38 • Region Span ~236.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

GAPO syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009263

Submitter: G2P

GAPO syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009263

Submitter: Orphanet

GAPO syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009263

Submitter: Labcorp Genetics (formerly Invitae)

capillary infantile hemangiomaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011191

Submitter: Ambry Genetics

GAPO syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009263

Submitter: PanelApp Australia

GAPO syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009263

Submitter: ClinGen

*ANTXR1* is located on chromosome 2 at 2p13.3 and encodes the Anthrax toxin receptor 1. This gene functions as a receptor for the protective antigen of anthrax toxin, facilitating the entry of the toxin into cells. Additionally, it plays a role in cell adhesion, extracellular matrix interactions, and angiogenesis, particularly in tumor vascularization. *ANTXR1* was first reported in relation with autosomal recessive GAPO syndrome in 2013 (Stránecký et al., 2013 PMID: 23602711). This is a rare syndrome with multiple congenital anomalies characterized by growth retardation, alopecia, pseudoanodontia and ocular manifestations (GAPO). The main facial features of the syndrome include frontal bossing, puffy eyelids, a depressed nasal bridge, anteverted wide nostrils, a thick upper lip, low-set ears, a very small jaw, and a premature aging appearance due to wrinkling of the skin. Nine unique variants (2 nonsense, 2 duplications, 2 canonical splice-site, 1 deletion, 1 missense, 1 intronic) reported in 10 families have been included in this curation (PMIDs: 23602711, 27587992, 30575274). Biallelic variants in *ANTXR1* most likely result in loss-of-function alleles. The maximum score for genetic evidence (12pts) has been reached; however, additional case reports exist in the literature (PMIDs: 25045128, 28870703, 38577561, 36094357, 38691016, 38423276, 29436111). This gene-disease relationship is also supported by experimental evidence including two mouse models, expression data, and evidence from biochemical function and functional alternation(PMIDs: 32244499, 19622764, 38653789). In summary, there is definitive evidence to support the relationship between *ANTXR1* and autosomal recessive GAPO syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the Syndromic Disorders Gene Curation Expert Panel on July 18th, 2025 (SOP Version 11)

GAPO syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009263

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hemangioma, capillary infantile, susceptibility to; Growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO syndrome)AD/AR

Manifestation: Craniofacial; Dental; Dermatologic; Musculoskeletal; Ophthalmologic

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: 9180938; 9298746; 18931684; 19367160; 23602711

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ANTXR1 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 79

Inborn genetic diseasesTotal: 73

GAPO syndromeTotal: 14

ANTXR1-related disorderTotal: 11

not specifiedTotal: 11

Capillary infantile hemangiomaTotal: 2

Bladder exstrophy-epispadias-cloacal exstrophy complexTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032208.3. 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		1 clinvar	1 clinvar	23 clinvar	4 clinvar	29
missense		2 clinvar	80 clinvar	5 clinvar	1 clinvar	88
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift		4 clinvar	2 clinvar			6
splice donor/acceptor (+/-2bp)		1 clinvar	6 clinvar			7
Total	1	10	89	28	5	133

Highest pathogenic variant AF is 0.0000013683747

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032208.3	RefSeq	NP_115584.1	18	MANE Select
ENST00000303714.9	Ensembl	ENSP00000301945.4	18	MANE Select
NM_001410840.1	RefSeq	NP_001397769.1	13	Standard
NM_018153.3	RefSeq	NP_060623.2	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOD-like receptor signaling pathway - Homo sapiens (human)
Disease
Uptake and actions of bacterial toxins
Uptake and function of anthrax toxins
Infectious disease

Biological Process

blood vessel development
reproductive process
actin cytoskeleton reorganization
substrate adhesion-dependent cell spreading
negative regulation of extracellular matrix assembly

Molecular Function

transmembrane signaling receptor activity
protein binding
collagen binding
metal ion binding
actin filament binding

Cellular Component

plasma membrane
external side of plasma membrane
cell surface
endosome membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303714
Coding exons: 18
Length: 236150
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.52	240	316	0.759	0.0000187	3638
Missense (PolyPhen)		78	132.44	0.58893		1543
Synonymous	-1.74	142	118	1.20	0.00000745	1103
Loss of Function	4.70	5	35.0	0.143	0.00000186	406

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in cell attachment and migration. Interacts with extracellular matrix proteins and with the actin cytoskeleton. Mediates adhesion of cells to type 1 collagen and gelatin, reorganization of the actin cytoskeleton and promotes cell spreading. Plays a role in the angiogenic response of cultured umbilical vein endothelial cells. {ECO:0000269|PubMed:15777794, ECO:0000269|PubMed:16762926}.;
Disease: DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269|PubMed:18931684}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: GAPO syndrome (GAPO) [MIM:230740]: A disease characterized by growth retardation, alopecia, failure of tooth eruption, and progressive optic atrophy in some patients. {ECO:0000269|PubMed:23602711}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.156
RVIS EVS: -0.91
RVIS percentile EVS: 10.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.545

Gene Damage Prediction

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