AEBP1

protein-coding

AE binding protein 1, the group of MicroRNA protein coding host genes|M14 carboxypeptidases

Gene summary

This gene encodes a member of carboxypeptidase A protein family. The encoded protein may function as a transcriptional repressor and play a role in adipogenesis and smooth muscle cell differentiation. Studies in mice suggest that this gene functions in wound healing and abdominal wall development. Overexpression of this gene is associated with glioblastoma. [provided by RefSeq, May 2013]

MANE transcript

NM_001129.5

Inheritance

ClinVar variants

P:50U:281B:267

Top phenotype

Ehlers-Danlos syndrome, classic-like, 2

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr7:44,104,345-44,114,562

External References & Databases

Ensembl (ENSG00000106624)

Transcript & Mutation Effects

hg38 • Region Span ~10.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ehlers-Danlos syndrome, classic-like, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054813

Submitter: Labcorp Genetics (formerly Invitae)

Ehlers-Danlos syndrome, classic-like, 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0054813

Submitter: Orphanet

Ehlers-Danlos syndrome, classic-like, 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0054813

Submitter: Ambry Genetics

Ehlers-Danlos syndrome, classic-like, 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0054813

Submitter: G2P

Ehlers-Danlos syndrome, classic-like, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054813

Submitter: Genomics England PanelApp

Ehlers-Danlos syndrome, classic-like, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054813

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ehlers-Danlos syndrome, classic-like, 2AR

Manifestation: Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal

Intervention: Cardiovascular; Gastrointestinal

Rationale: The condition can include manifestations such as bowel rupture and cardiovascular complications including aortic root dilatation, and awareness may allow surveillance, preventative measures, and early management

Refs: 27023906; 29606302

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AEBP1 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 678

not specifiedTotal: 234

AEBP1-related disorderTotal: 46

Ehlers-Danlos syndrome, classic-like, 2Total: 30

Inborn genetic diseasesTotal: 6

High myopiaTotal: 1

Autism spectrum disorderTotal: 1

Ehlers-Danlos syndrome, classic type, 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001129.5. 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			2 clinvar	244 clinvar	1 clinvar	247
missense		1 clinvar	270 clinvar	20 clinvar	1 clinvar	292
nonsense	7 clinvar	5 clinvar	1 clinvar			13
start loss		1 clinvar				1
frameshift	19 clinvar	7 clinvar	5 clinvar			31
splice donor/acceptor (+/-2bp)	2 clinvar	8 clinvar	3 clinvar	1 clinvar		14
Total	28	22	281	265	2	598

Highest pathogenic variant AF is 0.000012440596

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001129.5	RefSeq	NP_001120.3	21	MANE Select
ENST00000223357.8	Ensembl	ENSP00000223357.3	21	MANE Select
ENST00000413907.1	Ensembl	ENSP00000410349.1	2	Standard
ENST00000431035.1	Ensembl	ENSP00000416568.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
skeletal system development
peptide metabolic process
muscle organ development
protein processing

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
transcription corepressor activity
carboxypeptidase activity

Cellular Component

extracellular region
extracellular space
nucleus
cytoplasm
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000223357
Coding exons: 21
Length: 10202
Individuals with no LoFs: 124409
Homozygous LoFs: 5
Heterozygous LoFs: 1332
Defined: 125746
p: 0.00533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	654	730	0.896	0.0000467	7495
Missense (PolyPhen)		222	268.07	0.82815		2638
Synonymous	1.23	279	306	0.911	0.0000212	2287
Loss of Function	3.79	27	58.2	0.464	0.00000329	624

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0012	notable
Latino/Admixed American	0.0035	0.0034	notable
Ashkenazi Jewish	0.0049	0.0048	notable
East Asian	0.00044	0.00044	rare
Finnish	0.0053	0.0049	notable
European (Non-Finnish)	0.0084	0.0077	notable
South Asian	0.0046	0.0044	notable
Other	0.0063	0.0059	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1: As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellualr matrix. {ECO:0000269|PubMed:29606302}.;
Disease: DISEASE: Ehlers-Danlos syndrome, classic-like, 2 (EDSCLL2) [MIM:618000]: A variant form of Ehlers-Danlos syndrome, a connective tissue disorder. EDSCLL2 patients show severe joint and skin laxity, osteoporosis affecting the hips and spine, osteoarthritis, soft redundant skin that can be acrogeria-like, delayed wound healing with abnormal atrophic scarring, and shoulder, hip, knee, and ankle dislocations. Additional variable features include gastrointestinal and genitourinary manifestations (bowel rupture, gut dysmotility, cryptorchidism, and hernias), vascular complications (mitral valve prolapse and aortic root dilation), and skeletal anomalies. EDSCLL2 inheritance is autosomal recessive. {ECO:0000269|PubMed:27023906, ECO:0000269|PubMed:29606302}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.140
RVIS EVS: 0.12
RVIS percentile EVS: 62.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.108

Gene Damage Prediction

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