CDHR4

Summary

CDHR4 (cadherin related family member 4, HGNC:34527) is a protein-coding gene on chromosome 3p21.31, encoding Cadherin-related family member 4 (A6H8M9). Cadherins are calcium-dependent cell adhesion proteins.

Predicted to enable calcium ion binding activity. Predicted to be involved in cell adhesion. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 389118 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 142 total
• MANE Select transcript: NM_001007540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34527
Approved symbol	CDHR4
Name	cadherin related family member 4
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	VLLR9392
Ensembl gene	ENSG00000187492
Ensembl biotype	protein_coding
Entrez	389118

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000343366, ENST00000412678, ENST00000460430, ENST00000462108, ENST00000487256, ENST00000487666

RefSeq mRNA: 1 — MANE Select: NM_001007540 NM_001007540

CCDS: CCDS46829

Canonical transcript exons

ENST00000412678 — 19 exons

Exon	Start	End
ENSE00001367155	49799764	49799873
ENSE00001368163	49799247	49799437
ENSE00001616795	49791441	49791468
ENSE00001629523	49793583	49793722
ENSE00001645938	49792854	49793074
ENSE00001646668	49795628	49795764
ENSE00001670653	49794608	49794701
ENSE00001678315	49796922	49797032
ENSE00001690608	49795196	49795379
ENSE00001741833	49798826	49798917
ENSE00001746368	49793803	49794006
ENSE00001753570	49798994	49799156
ENSE00001759451	49793161	49793311
ENSE00001772903	49794947	49795100
ENSE00001796634	49795943	49796046
ENSE00001796912	49792468	49792610
ENSE00003564278	49791714	49791801
ENSE00003593266	49790732	49790887
ENSE00003654186	49791903	49791959

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 99.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2525 / max 50.2317, expressed in 67 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42277	0.1387	43
42278	0.1138	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.97	gold quality
fallopian tube	UBERON:0003889	88.96	gold quality
left uterine tube	UBERON:0001303	79.98	gold quality
right lung	UBERON:0002167	79.14	gold quality
right testis	UBERON:0004534	78.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.51	gold quality
left testis	UBERON:0004533	77.64	gold quality
testis	UBERON:0000473	76.88	gold quality
endocervix	UBERON:0000458	71.70	gold quality
lung	UBERON:0002048	64.95	gold quality
upper lobe of left lung	UBERON:0008952	64.62	gold quality
endometrium	UBERON:0001295	61.80	gold quality
right coronary artery	UBERON:0001625	61.25	gold quality
uterine cervix	UBERON:0000002	60.85	gold quality
popliteal artery	UBERON:0002250	59.70	gold quality
tibial artery	UBERON:0007610	59.66	gold quality
left coronary artery	UBERON:0001626	59.30	gold quality
thoracic aorta	UBERON:0001515	58.93	gold quality
ascending aorta	UBERON:0001496	58.78	gold quality
descending thoracic aorta	UBERON:0002345	58.69	gold quality
myometrium	UBERON:0001296	57.16	gold quality
stromal cell of endometrium	CL:0002255	56.84	gold quality
body of uterus	UBERON:0009853	56.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	56.28	gold quality
zone of skin	UBERON:0000014	56.03	gold quality
skin of leg	UBERON:0001511	55.93	gold quality
skin of abdomen	UBERON:0001416	55.86	gold quality
tibial nerve	UBERON:0001323	55.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	54.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting CDHR4, 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-3692-3P	99.98	70.27	2139
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-6856-3P	96.47	66.27	781

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdhr4	ENSMUSG00000032595
rattus_norvegicus	Cdhr4	ENSRNOG00000061650

Paralogs (61): PCDHB4 (ENSG00000081818), PCDHA6 (ENSG00000081842), PCDHGA2 (ENSG00000081853), PCDHB2 (ENSG00000112852), PCDHB3 (ENSG00000113205), PCDHB5 (ENSG00000113209), PCDHB6 (ENSG00000113211), PCDHB7 (ENSG00000113212), PCDHB15 (ENSG00000113248), PCDH12 (ENSG00000113555), PCDH17 (ENSG00000118946), PCDHB8 (ENSG00000120322), PCDHB10 (ENSG00000120324), PCDHB14 (ENSG00000120327), PCDHB12 (ENSG00000120328), PCDH8 (ENSG00000136099), PCDH10 (ENSG00000138650), PCDH15 (ENSG00000150275), PCDH19 (ENSG00000165194), CDH16 (ENSG00000166589), PCDHB1 (ENSG00000171815), PCDHB9 (ENSG00000177839), PCDHB13 (ENSG00000187372), PCDH18 (ENSG00000189184), PCDHB11 (ENSG00000197479), PCDHGA1 (ENSG00000204956), PCDHA9 (ENSG00000204961), PCDHA8 (ENSG00000204962), PCDHA7 (ENSG00000204963), PCDHA5 (ENSG00000204965), PCDHA4 (ENSG00000204967), PCDHA2 (ENSG00000204969), PCDHA1 (ENSG00000204970), PCDHA13 (ENSG00000239389), PCDHGC3 (ENSG00000240184), PCDHGC5 (ENSG00000240764), PCDHGC4 (ENSG00000242419), PCDHAC2 (ENSG00000243232), PCDHAC1 (ENSG00000248383), PCDHA11 (ENSG00000249158)

Protein

Protein identifiers

Cadherin-related family member 4 — A6H8M9 (reviewed: A6H8M9)

Alternative names: Cadherin-like protein 29

All UniProt accessions (4): A6H8M9, E9PFE8, H7C4N6, H7C5B2

UniProt curated annotations — full annotation on UniProt →

Function. Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
A6H8M9-1	1	yes
A6H8M9-2	2

RefSeq proteins (1): NP_001007541* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR050971	Cadherin-domain_protein	Family

Pfam: PF00028

UniProt features (13 total): domain 4, splice variant 2, topological domain 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6H8M9-F1	78.90	0.34

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 (1): 242

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_CELL_CELL_ADHESION, WANG_TUMOR_INVASIVENESS_UP, GOMF_CELL_ADHESION_MOLECULE_BINDING, MIKKELSEN_ES_ICP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, chr3p21, ZBTB12_TARGET_GENES, MIR6856_3P, MIR4641, GSE15324_NAIVE_VS_ACTIVATED_ELF4_KO_CD8_TCELL_DN, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_CEREBRUM_ASTROCYTES

GO Biological Process (2): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156)

GO Molecular Function (2): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
cell-cell adhesion	1
metal ion binding	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDHR4	IP6K1	Q92551	528
CDHR4	RNF123	Q5XPI4	522
CDHR4	MON1A	Q86VX9	496
CDHR4	CDH23	Q9H251	483
CDHR4	TRAIP	Q9BWF2	460
CDHR4	ZACN	Q401N2	452
CDHR4	KNCN	A6PVL3	432
CDHR4	CDHR2	Q9BYE9	432
CDHR4	CAMKV	Q8NCB2	419
CDHR4	C3orf62	Q6ZUJ4	399
CDHR4	EFCAB8	A8MWE9	397
CDHR4	MST1R	Q04912	378
CDHR4	R3HDM1	Q15032	364
CDHR4	KLHL3	Q9UH77	363
CDHR4	UCMA	Q8WVF2	354

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CDHR4	HSPA5	psi-mi:“MI:0914”(association)	0.350
CDHR4	TAPBP	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): HSPA5 (Affinity Capture-MS), MRC2 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), PTPRK (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), DNAJC16 (Affinity Capture-MS), COMMD3 (Affinity Capture-MS), METRNL (Affinity Capture-MS), NAGLU (Affinity Capture-MS), PON2 (Affinity Capture-MS), CNTNAP3B (Affinity Capture-MS), POLD3 (Affinity Capture-MS), ART5 (Affinity Capture-MS), SKP1 (Affinity Capture-MS), TTC37 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: A6H8M9, O55134, O88338, P34616, Q5DRA2, Q5DRC0, Q5DRC3, Q5DRC4, Q5DRF3, Q91Y13, Q9NPG4, Q9Y5F6, Q9Y5H2, Q9Y5I1, B2KI42, O02840, O54800, O55075, O60330, O88278, O93319, P09803, P15116, P19534, P33146, P33148, P33151, P33152, P55280, P55284, P55285, P55286, P55287, P55288, P70407, P97291, P97326, Q03763, Q13634, Q3SWX5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	117
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2783 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49792535:C:CT	donor_gain	1.0000
3:49792852:A:AC	donor_gain	1.0000
3:49792853:C:CC	donor_gain	1.0000
3:49793155:CCCTA:C	donor_loss	1.0000
3:49793156:CCTAC:C	donor_loss	1.0000
3:49793157:CTAC:C	donor_loss	1.0000
3:49793158:TACCT:T	donor_loss	1.0000
3:49793308:CATC:C	acceptor_gain	1.0000
3:49793310:TC:T	acceptor_gain	1.0000
3:49793311:CC:C	acceptor_gain	1.0000
3:49793312:C:CC	acceptor_gain	1.0000
3:49793312:CTGCA:C	acceptor_loss	1.0000
3:49793313:T:C	acceptor_loss	1.0000
3:49793802:CCG:C	donor_gain	1.0000
3:49793855:A:AC	donor_gain	1.0000
3:49794606:A:AC	donor_gain	1.0000
3:49794607:C:CC	donor_gain	1.0000
3:49795194:A:AC	donor_gain	1.0000
3:49795195:C:CC	donor_gain	1.0000
3:49795195:CA:C	donor_gain	1.0000
3:49795376:TCTG:T	acceptor_loss	1.0000
3:49795377:CTG:C	acceptor_gain	1.0000
3:49795377:CTGC:C	acceptor_loss	1.0000
3:49795378:TG:T	acceptor_gain	1.0000
3:49795379:GCTGC:G	acceptor_loss	1.0000
3:49795380:C:CC	acceptor_gain	1.0000
3:49795381:T:G	acceptor_loss	1.0000
3:49795383:CA:C	acceptor_gain	1.0000
3:49795384:A:AC	acceptor_gain	1.0000
3:49795384:A:C	acceptor_gain	1.0000

AlphaMissense

5118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49793055:G:C	F598L	0.955
3:49793055:G:T	F598L	0.955
3:49793057:A:G	F598L	0.955
3:49795215:A:G	C338R	0.940
3:49793963:G:C	F441L	0.939
3:49793963:G:T	F441L	0.939
3:49793965:A:G	F441L	0.939
3:49795214:C:G	C338S	0.938
3:49795215:A:T	C338S	0.938
3:49793056:A:G	F598S	0.937
3:49793593:A:T	I538N	0.936
3:49793822:A:C	F488L	0.935
3:49793822:A:T	F488L	0.935
3:49793824:A:G	F488L	0.935
3:49795367:A:T	V287D	0.932
3:49795047:C:T	C362Y	0.924
3:49795048:A:G	C362R	0.923
3:49795945:G:C	F236L	0.921
3:49795945:G:T	F236L	0.921
3:49795947:A:G	F236L	0.921
3:49796041:G:C	F204L	0.919
3:49796041:G:T	F204L	0.919
3:49796043:A:G	F204L	0.919
3:49790865:A:C	F778L	0.918
3:49790865:A:T	F778L	0.918
3:49790867:A:G	F778L	0.918
3:49791463:A:C	F763L	0.916
3:49791463:A:T	F763L	0.916
3:49791465:A:G	F763L	0.916
3:49796985:G:C	F181L	0.913

dbSNP variants (sampled 300 via entrez): RS1000345506 (3:49792062 T>A,C), RS1001005784 (3:49802427 G>T), RS1001071331 (3:49804000 C>A), RS1001100350 (3:49797073 G>C), RS1001266151 (3:49797857 G>A), RS1001298565 (3:49797594 G>C), RS1001425750 (3:49791114 G>T), RS1001550887 (3:49798176 A>G), RS1001686683 (3:49798664 C>A), RS1001695651 (3:49791034 T>C), RS1001876928 (3:49790823 T>C), RS1002119886 (3:49803386 C>T), RS1002407139 (3:49803574 G>A,C), RS1002691548 (3:49796992 C>T), RS1003580213 (3:49802532 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST005951_49	Body mass index	1.000000e-08
GCST006269_602	General cognitive ability	2.000000e-13
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Estradiol	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery