AEBP1

Summary

AEBP1 (AE binding protein 1, HGNC:303) is a protein-coding gene on chromosome 7p13, encoding Adipocyte enhancer-binding protein 1 (Q8IUX7). As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix.

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.

Source: NCBI Gene 165 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ehlers-Danlos syndrome, classic-like, 2 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 811 total — 33 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 95
• MANE Select transcript: NM_001129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:303
Approved symbol	AEBP1
Name	AE binding protein 1
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	ACLP
Ensembl gene	ENSG00000106624
Ensembl biotype	protein_coding
OMIM	602981
Entrez	165

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000223357, ENST00000413907, ENST00000431035, ENST00000434445, ENST00000449162, ENST00000450684, ENST00000453052, ENST00000454218, ENST00000455443, ENST00000910437, ENST00000910438, ENST00000910439, ENST00000910440, ENST00000910441, ENST00000935640, ENST00000935641

RefSeq mRNA: 1 — MANE Select: NM_001129 NM_001129

CCDS: CCDS5476

Canonical transcript exons

ENST00000223357 — 21 exons

Exon	Start	End
ENSE00000680729	44107439	44107510
ENSE00000680733	44108899	44108976
ENSE00000680736	44110015	44110124
ENSE00000680737	44110207	44110346
ENSE00000680738	44110725	44110809
ENSE00000680739	44110913	44111057
ENSE00000680741	44111507	44111630
ENSE00000832563	44106546	44106887
ENSE00000832564	44107809	44107931
ENSE00000832565	44108007	44108084
ENSE00001323037	44104345	44104918
ENSE00001882007	44113594	44114560
ENSE00003458441	44112142	44112321
ENSE00003489453	44112558	44112909
ENSE00003502428	44113252	44113351
ENSE00003560136	44112991	44113130
ENSE00003574885	44111154	44111239
ENSE00003605397	44109288	44109341
ENSE00003611869	44109107	44109184
ENSE00003667836	44111854	44112050
ENSE00003785901	44107629	44107700

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.8788 / max 6219.9757, expressed in 1233 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78393	59.0952	1224
78394	3.7717	775
78395	2.0119	569

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.97	gold quality
thoracic aorta	UBERON:0001515	99.77	gold quality
ascending aorta	UBERON:0001496	99.76	gold quality
right coronary artery	UBERON:0001625	99.76	gold quality
descending thoracic aorta	UBERON:0002345	99.75	gold quality
aorta	UBERON:0000947	99.67	gold quality
popliteal artery	UBERON:0002250	99.62	gold quality
tibial artery	UBERON:0007610	99.62	gold quality
artery	UBERON:0001637	99.60	gold quality
left coronary artery	UBERON:0001626	99.59	gold quality
coronary artery	UBERON:0001621	99.57	gold quality
saphenous vein	UBERON:0007318	99.46	gold quality
endocervix	UBERON:0000458	99.43	gold quality
right ovary	UBERON:0002118	99.33	gold quality
body of uterus	UBERON:0009853	99.27	gold quality
left ovary	UBERON:0002119	99.21	gold quality
gall bladder	UBERON:0002110	99.10	gold quality
left uterine tube	UBERON:0001303	99.06	gold quality
mucosa of stomach	UBERON:0001199	99.03	gold quality
stromal cell of endometrium	CL:0002255	98.80	gold quality
ectocervix	UBERON:0012249	98.69	gold quality
urethra	UBERON:0000057	98.67	gold quality
blood vessel layer	UBERON:0004797	98.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.54	gold quality
omental fat pad	UBERON:0010414	98.52	gold quality
peritoneum	UBERON:0002358	98.51	gold quality
metanephros cortex	UBERON:0010533	98.51	gold quality
peripheral nervous system	UBERON:0000010	98.38	gold quality
nerve	UBERON:0001021	98.38	gold quality
tibial nerve	UBERON:0001323	98.38	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	1588.45
E-HCAD-36	yes	1556.72
E-GEOD-124263	yes	1284.95
E-MTAB-9841	yes	1102.88
E-MTAB-8142	yes	107.36
E-HCAD-1	yes	86.62
E-GEOD-135922	yes	62.47
E-GEOD-134144	yes	38.64
E-CURD-112	yes	37.74
E-MTAB-10287	yes	24.65
E-MTAB-9543	yes	21.47
E-MTAB-9067	yes	16.37
E-CURD-46	yes	15.73
E-MTAB-5061	yes	11.21
E-HCAD-11	yes	8.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
APOE
CD36
FABP4	Repression
TFAP2A
TNF

Upstream regulators (CollecTRI, top): CEBPA, SP1, SP3

miRNA regulators (miRDB)

10 targeting AEBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-1587	96.95	64.03	932

Literature-anchored findings (GeneRIF, showing 31)

• Most ACLP knockout mice die perinatally due to abdominal issues. (PMID:11438679)
• Transgenic overexpression of AEBP1 during adipogenesis coupled with a high-fat diet results in massive obesity in female transgenic mice via adipocyte hyperplasia. (PMID:16307171)
• ACLP and its discoidin-like domain may be novel targets for anti-myofibroblast-based therapies for the treatment of pulmonary fibrosis. (PMID:19179605)
• This review focuses on the recently reported regulatory functions that adipocyte enhancer-binding protein 1 (AEBP1) exerts on PPARgamma1 and LXRalpha transcriptional activity in the context of macrophage cholesterol homeostasis and inflammation. (PMID:20419060)
• Both cellular proliferation and survival were affected in AEBP1-silenced U87MG and U138MG cell lines and a significant percentage of these cells were directed towards apoptosis. (PMID:22723309)
• There is no statistically significant differences in the frequency of variants in AEBP1 among the gastroschisis case group compared to a Caucasian control group. (PMID:22821744)
• ACLP stimulates the fibroblast-to-myofibroblast transition by promoting SMA expression via TGFbeta signaling and promoting collagen expression through a TGFbeta receptor-independent pathway. (PMID:24344132)
• AEBP1 protein is expressed in the pyramidal neurons of human central nervous system and increased in neurons and glial cells of hippocampi and parahippocampal cortices, correlating with the progression of Alzheimer’s disease. (PMID:27997051)
• The present study elucidates the role of canonical WNT pathway activation by ACLP in NASH pathology, indicating that NASH can be treated by targeting ACLP-induced canonical WNT pathway activation in HSCs. (PMID:29553485)
• These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive Ehlers-Danlos Syndrome subtype. (PMID:29606302)
• Studies identify ACLP as a stromal derived mediator of adipose progenitor differentiation that may limit adipocyte expansion during white adipose tissue fibrosis. (PMID:29799877)
• this study shows that AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-kappaB pathway and predicts poor outcome of the patients (PMID:30097586)
• Our results further verify that autosomal-recessive inherited Loss of Function variants in the AEBP1 gene cause clinical features of different Ehlers-Danlos Syndrome (EDS) subtypes, but also of the marfanoid spectrum (PMID:30548383)
• This report further expands the clinical, molecular and ultrastructural spectrum associated with AEBP1 defects and highlights the complex and variable phenotype associated with this new Ehlers-Danlos syndromes variant. (PMID:30668708)
• Association of AEBP1 and NRN1 RNA expression with Alzheimer’s disease and neurofibrillary tangle density in middle temporal gyrus. (PMID:31176712)
• these data indicated that AEBP1 may be a new prognostic factor and a potential gene therapy target in colon adenocarcinoma (PMID:31219650)
• AEBP1 expression is regulated by glucose, palmitate, and miR-372-3p, a pathway that has a role in the pathogenesis of hepatic fibrosis in nonalcoholic steatohepatitis (PMID:31299062)
• AEBP1 Promotes the Occurrence and Development of Abdominal Aortic Aneurysm by Modulating Inflammation via the NF-kappaB Pathway. (PMID:31462616)
• AEBP1 down regulation induced cell death pathway depends on PTEN status of glioma cells. (PMID:31601918)
• Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis. (PMID:31864713)
• Adipocyte enhancer-binding protein 1 (AEBP1) expression is upregulated in tumor endothelial cells of colorectal cancer (CRC). Knockdown of AEBP1 suppresses proliferation, migration, and in vitro tube formation by Human umbilical vein endothelial cells (HUVECs). AEBP1 knockdown suppresses tumorigenesis and microvessel formation in vivo. Depletion of AEBP1 in HUVECs downregulates genes associated with angiogenesis. (PMID:32086986)
• AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-kappaB Pathway. (PMID:33224311)
• Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease. (PMID:34332599)
• Molecular Characterization of AEBP1 at Transcriptional Level in Glioma. (PMID:34373835)
• Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level. (PMID:34601654)
• AEBP1 Is One of the Epithelial-Mesenchymal Transition Regulatory Genes in Colon Adenocarcinoma. (PMID:34938806)
• ACLP promotes activation of cancer-associated fibroblasts and tumor metastasis via ACLP-PPARgamma-ACLP feedback loop in pancreatic cancer. (PMID:35732215)
• Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator. (PMID:37917183)
• AEBP1 promotes papillary thyroid cancer progression by activating BMP4 signaling. (PMID:38237535)
• Dysregulated AEBP1 and COLEC12 Genes in Late-Onset Alzheimer’s Disease: Insights from Brain Cortex and Peripheral Blood Analysis. (PMID:38568322)
• AEBP1 upregulation contributes to cervical cancer progression by facilitating cell proliferation, migration, and invasion. (PMID:38684171)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	aebp1b	ENSDARG00000006901
danio_rerio	aebp1a	ENSDARG00000091726
mus_musculus	Aebp1	ENSMUSG00000020473
rattus_norvegicus	Aebp1	ENSRNOG00000013720

Paralogs (7): CPXM1 (ENSG00000088882), CPD (ENSG00000108582), CPE (ENSG00000109472), CPZ (ENSG00000109625), CPN1 (ENSG00000120054), CPXM2 (ENSG00000121898), CPM (ENSG00000135678)

Protein

Protein identifiers

Adipocyte enhancer-binding protein 1 — Q8IUX7 (reviewed: Q8IUX7)

Alternative names: Aortic carboxypeptidase-like protein

All UniProt accessions (7): Q8IUX7, C9JLQ8, H7C0W8, H7C1J5, H7C391, H7C3D7, H7C4B5

UniProt curated annotations — full annotation on UniProt →

Function. As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix. May positively regulate MAP-kinase activity in adipocytes, leading to enhanced adipocyte proliferation and reduced adipocyte differentiation. May also positively regulate NF-kappa-B activity in macrophages by promoting the phosphorylation and subsequent degradation of I-kappa-B-alpha (NFKBIA), leading to enhanced macrophage inflammatory responsiveness. Can act as a transcriptional repressor.

Subunit / interactions. Isoform 1: Interacts with different types of collagen, including collagens I, III, and V. Isoform 2: Interacts with GNG5, NFKBIA, MAPK1, MAPK3 and PTEN. Interaction with MAPK1 may stimulate DNA-binding. May interact with calmodulin. Binds to DNA in vitro.

Subcellular location. Secreted Cytoplasm. Nucleus.

Tissue specificity. Expressed in osteoblast and visceral fat.

Post-translational modifications. Phosphorylated by MAPK1 in vitro.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The F5/8 type C domain binds to different types of collagen, including collagens I, III, and V.

Similarity. Belongs to the peptidase M14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IUX7-1	1	yes
Q8IUX7-2	2

RefSeq proteins (1): NP_001120* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR000834	Peptidase_M14	Domain
IPR008969	CarboxyPept-like_regulatory	Homologous_superfamily
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR050753	Peptidase_M14_domain	Family
IPR057246	CARBOXYPEPT_ZN_1	Binding_site

Pfam: PF00246, PF00754, PF13620

UniProt features (39 total): compositionally biased region 11, region of interest 7, sequence variant 6, sequence conflict 6, splice variant 3, domain 2, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUX7-F1	67.99	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 528, 922

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 446 (showing top): MODULE_172, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOMF_METALLOPEPTIDASE_ACTIVITY, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MODULE_329, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, SHEPARD_BMYB_MORPHOLINO_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_PEPTIDE_METABOLIC_PROCESS, MODULE_492, BORLAK_LIVER_CANCER_EGF_UP, GOBP_PROTEIN_MATURATION

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), proteolysis (GO:0006508), regulation of collagen fibril organization (GO:1904026)

GO Molecular Function (9): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), carboxypeptidase activity (GO:0004180), calmodulin binding (GO:0005516), collagen binding (GO:0005518), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metallocarboxypeptidase activity (GO:0004181), extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein metabolic process	1
collagen fibril organization	1
regulation of extracellular matrix organization	1
transcription cis-regulatory region binding	1
negative regulation of transcription by RNA polymerase II	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
exopeptidase activity	1
protein binding	1
protein-containing complex binding	1
transition metal ion binding	1
nucleic acid binding	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
structural molecule activity	1
extracellular matrix	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AEBP1	TCF3	P15883	642
AEBP1	FZD8	Q9H461	518
AEBP1	COL14A1	Q05707	467
AEBP1	LRP6	O75581	463
AEBP1	FKBP14	Q9NWM8	447
AEBP1	COL5A2	P05997	444
AEBP1	FMOD	Q06828	444
AEBP1	LRRTM4	Q86VH4	437
AEBP1	COL12A1	Q99715	436
AEBP1	TP53TG5	Q9Y2B4	434
AEBP1	COL5A1	P20908	430
AEBP1	CFAP61	Q8NHU2	413
AEBP1	CHST14	Q8NCH0	407
AEBP1	NUDCD3	Q8IVD9	404
AEBP1	SP110	Q9HB58	396

IntAct

5 interactions, top by confidence:

A	B	Type	Score
VASP	AEBP1	psi-mi:“MI:0407”(direct interaction)	0.440
	AEBP1	psi-mi:“MI:0915”(physical association)	0.370
CTNNA1	MYO1G	psi-mi:“MI:0914”(association)	0.350
hflC	AEBP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): AEBP1 (Affinity Capture-MS), AEBP1 (Affinity Capture-MS), AEBP1 (Protein-peptide), HIST1H2BC (Cross-Linking-MS (XL-MS)), HIST1H2BK (Cross-Linking-MS (XL-MS)), AEBP1 (Affinity Capture-RNA), AEBP1 (Two-hybrid)

ESM2 similar proteins: A2RUV9, F8W3R9, O18738, O43278, O54858, O88393, O97827, P00734, P00735, P0C5J5, P12259, P18292, P26342, P35054, P51511, Q08629, Q08E66, Q09101, Q14118, Q24567, Q24568, Q28685, Q29243, Q5R537, Q5RD69, Q62165, Q62288, Q640N1, Q66K79, Q701R2, Q7TQN3, Q80TS3, Q8BKV0, Q8IUX7, Q8N436, Q8R4V4, Q8TEU8, Q91ZV2, Q91ZV3, Q92563

Diamond homologs: A2RUV9, A5A6K7, O14786, O17754, O18806, O35276, O35375, O35474, O43854, O54858, O54991, O60462, O75976, O88783, O89001, P00451, P02886, P02887, P02888, P04836, P12259, P12263, P14384, P15087, P15169, P16870, P21956, P28824, P29068, P37892, P39041, P42787, P70490, P78357, P79385, P79795, P83852, P97333, P97846, P98092

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPK1	“up-regulates activity”	AEBP1	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

811 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	13
Uncertain significance	301
Likely benign	367
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1030176	NM_001129.5(AEBP1):c.2853C>A (p.Tyr951Ter)	Pathogenic
1030177	NM_001129.5(AEBP1):c.1067G>A (p.Trp356Ter)	Pathogenic
146855	GRCh38/hg38 7p14.1-11.2(chr7:40534157-56107122)x1	Pathogenic
148230	GRCh38/hg38 7p14.1-13(chr7:39063400-45363096)x1	Pathogenic
154192	GRCh38/hg38 7p14.1-13(chr7:38177999-45304100)x1	Pathogenic
1676869	NM_001129.5(AEBP1):c.1783C>T (p.Arg595Ter)	Pathogenic
1959131	NM_001129.5(AEBP1):c.2387dup (p.Asp796fs)	Pathogenic
2004953	NM_001129.5(AEBP1):c.2731del (p.Val911fs)	Pathogenic
2036739	NM_001129.5(AEBP1):c.2045_2046del (p.Glu682fs)	Pathogenic
2117669	NM_001129.5(AEBP1):c.2026del (p.Ala676fs)	Pathogenic
2571277	NM_001129.5(AEBP1):c.1455G>A (p.Trp485Ter)	Pathogenic
2695350	NM_001129.5(AEBP1):c.218del (p.Gly73fs)	Pathogenic
2697420	NM_001129.5(AEBP1):c.2608G>T (p.Glu870Ter)	Pathogenic
2747490	NM_001129.5(AEBP1):c.2608del (p.Glu870fs)	Pathogenic
2795016	NM_001129.5(AEBP1):c.2383dup (p.Glu795fs)	Pathogenic
2996828	NM_001129.5(AEBP1):c.996_999del (p.Asp333fs)	Pathogenic
3020767	NM_001129.5(AEBP1):c.1630+2T>A	Pathogenic
3233787	NM_001129.5(AEBP1):c.1816_1817del (p.Asp606fs)	Pathogenic
3643102	NM_001129.5(AEBP1):c.2650del (p.Ser884fs)	Pathogenic
3649776	NM_001129.5(AEBP1):c.1102C>T (p.Arg368Ter)	Pathogenic
3657551	NM_001129.5(AEBP1):c.185_186del (p.Pro62fs)	Pathogenic
3664539	NM_001129.5(AEBP1):c.1123del (p.Glu375fs)	Pathogenic
3680182	NM_001129.5(AEBP1):c.561dup (p.Ser188fs)	Pathogenic
3706022	NM_001129.5(AEBP1):c.2174dup (p.Asn725fs)	Pathogenic
395336	GRCh37/hg19 7p14.3-13(chr7:32911003-44576005)x1	Pathogenic
4696062	NM_001129.5(AEBP1):c.899_900del (p.Pro300fs)	Pathogenic
4729564	NM_001129.5(AEBP1):c.1161dup (p.Ile388fs)	Pathogenic
4730217	NM_001129.5(AEBP1):c.148dup (p.Arg50fs)	Pathogenic
4848489	NC_000007.13:g.(?44143943)(44154160_?)del	Pathogenic
545021	NM_001129.5(AEBP1):c.1630+1G>A	Pathogenic

SpliceAI

3219 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44104915:GAAG:G	donor_gain	1.0000
7:44104916:AAGGT:A	donor_loss	1.0000
7:44104919:G:GG	donor_gain	1.0000
7:44104919:GTAA:G	donor_loss	1.0000
7:44106544:A:AG	acceptor_gain	1.0000
7:44106545:G:GG	acceptor_gain	1.0000
7:44106757:G:GT	donor_gain	1.0000
7:44106778:G:GT	donor_gain	1.0000
7:44106793:G:GT	donor_gain	1.0000
7:44107506:GCCTG:G	donor_gain	1.0000
7:44107627:A:AG	acceptor_gain	1.0000
7:44107628:G:GG	acceptor_gain	1.0000
7:44107696:GGACT:G	donor_gain	1.0000
7:44107697:GACT:G	donor_gain	1.0000
7:44107697:GACTG:G	donor_gain	1.0000
7:44107701:G:GG	donor_gain	1.0000
7:44107701:GTGA:G	donor_loss	1.0000
7:44107702:T:G	donor_loss	1.0000
7:44107705:G:GG	donor_gain	1.0000
7:44108005:A:AG	acceptor_gain	1.0000
7:44108006:G:GG	acceptor_gain	1.0000
7:44108006:GA:G	acceptor_gain	1.0000
7:44108006:GAGC:G	acceptor_gain	1.0000
7:44108080:TGACA:T	donor_gain	1.0000
7:44108081:GACA:G	donor_gain	1.0000
7:44108081:GACAG:G	donor_gain	1.0000
7:44108082:ACA:A	donor_gain	1.0000
7:44108083:CA:C	donor_gain	1.0000
7:44108083:CAG:C	donor_loss	1.0000
7:44108084:AG:A	donor_loss	1.0000

AlphaMissense

7570 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44113615:G:C	R944P	1.000
7:44110243:T:A	W433R	0.999
7:44110243:T:C	W433R	0.999
7:44110245:G:C	W433C	0.999
7:44110245:G:T	W433C	0.999
7:44110989:G:C	R521P	0.999
7:44111567:A:C	S593R	0.999
7:44111569:C:A	S593R	0.999
7:44111569:C:G	S593R	0.999
7:44111995:G:C	R661P	0.999
7:44112588:T:A	W750R	0.999
7:44112588:T:C	W750R	0.999
7:44113091:G:C	W890C	0.999
7:44113091:G:T	W890C	0.999
7:44113259:G:C	R906P	0.999
7:44113270:G:A	G910R	0.999
7:44113270:G:C	G910R	0.999
7:44113270:G:T	G910W	0.999
7:44113716:T:C	C978R	0.999
7:44113718:C:G	C978W	0.999
7:44110307:T:C	F454S	0.998
7:44110760:G:T	S479I	0.998
7:44110779:G:C	W485C	0.998
7:44110779:G:T	W485C	0.998
7:44111023:C:G	C532W	0.998
7:44111531:T:C	C581R	0.998
7:44111547:G:C	R586P	0.998
7:44111869:G:C	R619P	0.998
7:44111940:T:C	C643R	0.998
7:44111942:C:G	C643W	0.998

dbSNP variants (sampled 300 via entrez): RS1000097122 (7:44115028 C>T), RS1000193187 (7:44102946 G>A), RS1000204439 (7:44103265 G>C,T), RS1000323560 (7:44108688 C>A,T), RS1000530722 (7:44104399 C>A,G,T), RS1000704506 (7:44104322 C>A,G), RS1001333917 (7:44104227 G>C), RS1001386189 (7:44110489 C>G,T), RS1001911932 (7:44103685 C>T), RS1002029505 (7:44103464 C>A,T), RS1002177683 (7:44114065 G>A,C), RS1002936697 (7:44113034 C>G), RS1003007320 (7:44105127 G>A), RS1003049485 (7:44105489 A>T), RS1003183601 (7:44112596 G>A)

Disease associations

OMIM: gene MIM:602981 | disease phenotypes: MIM:618000, MIM:130010, MIM:130000

GenCC curated gene-disease

Disease	Classification	Inheritance
Ehlers-Danlos syndrome, classic-like, 2	Strong	Autosomal recessive

Mondo (4): Ehlers-Danlos syndrome, classic-like, 2 (MONDO:0054813), autism spectrum disorder (MONDO:0005258), Ehlers-Danlos syndrome, classic type, 2 (MONDO:0019568), Ehlers-Danlos syndrome, classic type, 1 (MONDO:0019567)

Orphanet (5): Classical-like Ehlers-Danlos syndrome type 2 (Orphanet:536532), Classical Ehlers-Danlos syndrome (Orphanet:287), OBSOLETE: Ehlers-Danlos syndrome type 2 (Orphanet:90318), NON RARE IN EUROPE: Autism (Orphanet:106), OBSOLETE: Ehlers-Danlos syndrome type 1 (Orphanet:90309)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000347	Micrognathia
HP:0000400	Macrotia
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0000692	Tooth malposition
HP:0000704	Periodontitis
HP:0000767	Pectus excavatum
HP:0000819	Diabetes mellitus
HP:0000938	Osteopenia
HP:0000953	Hyperpigmentation of the skin
HP:0000960	Sacral dimple
HP:0000974	Hyperextensible skin
HP:0000978	Bruising susceptibility
HP:0000987	Atypical scarring of skin
HP:0000993	Molluscoid pseudotumors
HP:0001015	Prominent superficial veins
HP:0001027	Soft, doughy skin
HP:0001058	Poor wound healing
HP:0001075	Atrophic scars
HP:0001097	Keratoconjunctivitis sicca
HP:0001166	Arachnodactyly
HP:0001252	Hypotonia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007581_11	Carpal tunnel syndrome	8.000000e-09

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536194	Ehlers-Danlos syndrome type 1 (supp.)
C536195	Ehlers-Danlos syndrome type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M14: Carboxypeptidase A

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Valproic Acid	decreases expression, affects expression	2
Cadmium Chloride	decreases expression, increases abundance	2
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
arenobufagin	decreases stability, decreases expression, decreases reaction, increases reaction, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Cadmium	decreases expression, increases abundance	1
Dactinomycin	affects cotreatment, decreases stability	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	affects cotreatment, increases expression	1
Phthalic Acids	increases methylation	1
Polychlorinated Biphenyls	affects expression	1
Smoke	decreases expression	1
Vitamin E	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Silver Compounds	increases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder