LDLRAD2

Summary

LDLRAD2 (low density lipoprotein receptor class A domain containing 2, HGNC:32071) is a protein-coding gene on chromosome 1p36.12, encoding Low-density lipoprotein receptor class A domain-containing protein 2 (Q5SZI1).

Predicted to be located in membrane.

Source: NCBI Gene 401944 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 100 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001013693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32071
Approved symbol	LDLRAD2
Name	low density lipoprotein receptor class A domain containing 2
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187942
Ensembl biotype	protein_coding
Entrez	401944

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000344642, ENST00000484271, ENST00000543870

RefSeq mRNA: 1 — MANE Select: NM_001013693 NM_001013693

CCDS: CCDS30624

Canonical transcript exons

ENST00000344642 — 5 exons

Exon	Start	End
ENSE00001366572	21812265	21812536
ENSE00001385485	21821450	21821611
ENSE00001388905	21815943	21816074
ENSE00001391037	21814398	21814823
ENSE00001391607	21822202	21825225

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 92.05.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.05	gold quality
popliteal artery	UBERON:0002250	91.90	gold quality
tibial artery	UBERON:0007610	91.89	gold quality
right coronary artery	UBERON:0001625	91.51	gold quality
descending thoracic aorta	UBERON:0002345	91.41	gold quality
thoracic aorta	UBERON:0001515	90.72	gold quality
ascending aorta	UBERON:0001496	90.59	gold quality
left coronary artery	UBERON:0001626	86.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.63	gold quality
left uterine tube	UBERON:0001303	84.55	gold quality
tibial nerve	UBERON:0001323	84.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.25	gold quality
lower esophagus	UBERON:0013473	84.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.86	gold quality
mucosa of stomach	UBERON:0001199	83.67	gold quality
myometrium	UBERON:0001296	83.19	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.65	gold quality
body of uterus	UBERON:0009853	82.06	gold quality
adipose tissue	UBERON:0001013	81.39	gold quality
apex of heart	UBERON:0002098	81.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.23	gold quality
omental fat pad	UBERON:0010414	79.80	gold quality
fundus of stomach	UBERON:0001160	79.79	gold quality
colon	UBERON:0001155	78.59	gold quality
smooth muscle tissue	UBERON:0001135	78.34	gold quality
thoracic mammary gland	UBERON:0005200	78.12	gold quality
urinary bladder	UBERON:0001255	78.07	gold quality
minor salivary gland	UBERON:0001830	77.55	gold quality
right atrium auricular region	UBERON:0006631	77.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	2814.61
E-ANND-3	yes	2.99
E-CURD-112	no	3.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting LDLRAD2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963

Literature-anchored findings (GeneRIF, showing 1)

• LDLRAD2 promotes pancreatic cancer progression through Akt/mTOR signaling pathway. (PMID:33392788)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ldlrad2	ENSDARG00000090297
mus_musculus	Ldlrad2	ENSMUSG00000094035
rattus_norvegicus	Ldlrad2	ENSRNOG00000033503

Paralogs (1): CD320 (ENSG00000167775)

Protein

Protein identifiers

Low-density lipoprotein receptor class A domain-containing protein 2 — Q5SZI1 (reviewed: Q5SZI1)

All UniProt accessions (1): Q5SZI1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the LDLR family.

RefSeq proteins (1): NP_001013715* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR042333	LRAD2/Mig-13-like	Family

Pfam: PF00057

UniProt features (14 total): disulfide bond 3, topological domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SZI1-F1	79.62	0.63

Functional residue map

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

Disulfide bonds (3): 179–199, 191–213, 173–184

Glycosylation sites (1): 97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): AGGAAGC_MIR5163P, TAATAAT_MIR126, AAGCCAT_MIR135A_MIR135B, CAGGTCC_MIR492, CCAGGGG_MIR331, chr1p36, MIR4795_3P, MIR126_5P, MIR15A_5P, MIR195_5P, MIR15B_5P, MIR16_5P, MIR6838_5P, MIR6825_5P, MIR424_5P

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDLRAD2	LRP3	O75074	508
LDLRAD2	UBL4B	Q8N7F7	447
LDLRAD2	NOXA1	Q86UR1	433
LDLRAD2	CTNNA3	Q9UI47	394
LDLRAD2	JSRP1	Q96MG2	392
LDLRAD2	TMEM273	Q5T292	378
LDLRAD2	SSC4D	Q8WTU2	374
LDLRAD2	CCDC138	Q96M89	370
LDLRAD2	SCART1	Q4G0T1	359
LDLRAD2	ABCG5	Q9H222	343
LDLRAD2	EFCAB6	Q5THR3	323
LDLRAD2	GPATCH4	Q5T3I0	323
LDLRAD2	CFAP263	Q9H0I3	322
LDLRAD2	GOLGA8B	A8MQT2	322
LDLRAD2	MACO1	Q8N5G2	320

IntAct

0 interactions, top by confidence:

BioGRID (2): LDLRAD2 (Protein-RNA), LDLRAD2 (Affinity Capture-MS)

ESM2 similar proteins: A1L515, A4D2P6, A6QQD2, A8VU90, E1BDF2, O75808, O88995, P0CG25, P22083, Q0IIA6, Q2TA57, Q3B7L1, Q3MIP1, Q3U5Q7, Q3UR50, Q3UR97, Q3UV16, Q400G9, Q5BKX5, Q5EBM0, Q5GH72, Q5SZI1, Q5TM19, Q5U4P2, Q62994, Q659K9, Q6PRD1, Q7Z736, Q861W0, Q86UR1, Q8BNN1, Q8C0R7, Q8CG70, Q8IUW3, Q8IVL6, Q8N398, Q8NAG6, Q8NCW0, Q8R2H1, Q8VCE9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	79
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2506374	NM_005529.7(HSPG2):c.13163_13164del (p.Pro4388fs)	Likely pathogenic

SpliceAI

1464 predictions. Top by Δscore:

Variant	Effect	Δscore
1:21812532:GACAG:G	donor_gain	1.0000
1:21812534:CAG:C	donor_gain	1.0000
1:21812534:CAGG:C	donor_loss	1.0000
1:21812535:AG:A	donor_gain	1.0000
1:21812536:GG:G	donor_gain	1.0000
1:21812537:G:GG	donor_gain	1.0000
1:21823611:CTTA:C	donor_loss	1.0000
1:21823612:TTA:T	donor_loss	1.0000
1:21823613:TA:T	donor_loss	1.0000
1:21823614:A:AC	donor_gain	1.0000
1:21823615:C:CC	donor_gain	1.0000
1:21823615:CCGAT:C	donor_gain	1.0000
1:21823716:CTCC:C	acceptor_gain	1.0000
1:21823717:TCC:T	acceptor_gain	1.0000
1:21823718:CC:C	acceptor_gain	1.0000
1:21823718:CCC:C	acceptor_gain	1.0000
1:21823719:CC:C	acceptor_gain	1.0000
1:21823720:C:CC	acceptor_gain	1.0000
1:21823720:CT:C	acceptor_loss	1.0000
1:21824301:CCTA:C	donor_loss	1.0000
1:21824302:CTA:C	donor_loss	1.0000
1:21824303:TA:T	donor_loss	1.0000
1:21824304:A:AC	donor_gain	1.0000
1:21824305:C:CC	donor_gain	1.0000
1:21824381:C:CT	acceptor_gain	1.0000
1:21824530:CA:C	donor_gain	1.0000
1:21824534:CACCA:C	donor_loss	1.0000
1:21824535:A:AC	donor_gain	1.0000
1:21824535:A:T	donor_loss	1.0000
1:21824536:C:CC	donor_gain	1.0000

AlphaMissense

1720 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:21814794:T:G	F161C	0.988
1:21814794:T:C	F161S	0.986
1:21814793:T:C	F161L	0.984
1:21814795:C:A	F161L	0.984
1:21814795:C:G	F161L	0.984
1:21814553:T:C	F81L	0.982
1:21814555:C:A	F81L	0.982
1:21814555:C:G	F81L	0.982
1:21814548:T:C	F79S	0.976
1:21814554:T:C	F81S	0.974
1:21816025:C:A	N198K	0.969
1:21816025:C:G	N198K	0.969
1:21814814:T:C	F168L	0.968
1:21814816:C:A	F168L	0.968
1:21814816:C:G	F168L	0.968
1:21816026:T:A	C199S	0.968
1:21816027:G:C	C199S	0.968
1:21814559:T:C	F83L	0.964
1:21814561:C:A	F83L	0.964
1:21814561:C:G	F83L	0.964
1:21816027:G:A	C199Y	0.964
1:21814475:T:C	F55L	0.963
1:21814477:C:A	F55L	0.963
1:21814477:C:G	F55L	0.963
1:21814554:T:G	F81C	0.963
1:21815966:T:A	C179S	0.963
1:21815967:G:C	C179S	0.963
1:21815961:T:G	F177C	0.962
1:21814482:T:G	F57C	0.961
1:21814562:T:C	F84L	0.960

dbSNP variants (sampled 300 via entrez): RS1000087359 (1:21825178 G>C), RS1000338291 (1:21819971 C>G,T), RS1000480492 (1:21811567 G>A), RS1000577660 (1:21822757 G>T), RS1000580644 (1:21811918 G>C), RS1000586727 (1:21817480 C>T), RS1000882484 (1:21824164 C>A,T), RS1001010448 (1:21822995 C>T), RS1001099274 (1:21823959 C>A,T), RS1001226439 (1:21820573 C>G,T), RS1001802881 (1:21810397 G>A), RS1001841149 (1:21825602 CAG>C), RS1002011876 (1:21816307 A>G), RS1002177442 (1:21819633 G>A,T), RS1002273439 (1:21821736 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:224410, MIM:255800

GenCC curated gene-disease

Mondo (5): Silverman-Handmaker type dyssegmental dysplasia (MONDO:0009140), connective tissue disorder (MONDO:0003900), Schwartz-Jampel syndrome type 1 (MONDO:0100435), Schwartz-Jampel syndrome (MONDO:0009717), microcephaly (MONDO:0001149)

Orphanet (2): Dyssegmental dysplasia, Silverman-Handmaker type (Orphanet:1865), Schwartz-Jampel syndrome (Orphanet:800)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005196_179	Coronary artery disease	9.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537998	Dyssegmental dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation	2
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT01424033	PHASE2/PHASE3	TERMINATED	A Clinical Trial for CTD-ILD Treatment
NCT04915482	PHASE2/PHASE3	UNKNOWN	TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT06574581	PHASE1/PHASE2	RECRUITING	ADSCs Therapy in Patients With CTD-ILD
NCT00001330	Not specified	COMPLETED	Study of Silicone-Associated Connective Tissue Diseases
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00001978	Not specified	TERMINATED	Determination of Kidney Function
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease
NCT00341679	Not specified	COMPLETED	Studies of the Natural History and Pathogenesis of Autoimmune/Connective Tissue Diseases
NCT00470327	Not specified	RECRUITING	A Study of the Natural Progression of Interstitial Lung Disease (ILD)
NCT00491309	Not specified	UNKNOWN	Exercise and Respiratory Therapy in Patients With Rheumatoid Arthritis / Collagenosis and Pulmonary Hypertension