CHAD

Summary

CHAD (chondroadherin, HGNC:1909) is a protein-coding gene on chromosome 17q21.33, encoding Chondroadherin (O15335). Promotes attachment of chondrocytes, fibroblasts, and osteoblasts.

Chondroadherin is a cartilage matrix protein thought to mediate adhesion of isolated chondrocytes. The protein contains 11 leucine-rich repeats flanked by cysteine-rich regions. The chondroadherin messenger RNA is present in chondrocytes at all ages.

Source: NCBI Gene 1101 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001267

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1909
Approved symbol	CHAD
Name	chondroadherin
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	SLRR4A
Ensembl gene	ENSG00000136457
Ensembl biotype	protein_coding
OMIM	602178
Entrez	1101

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000258969, ENST00000506187, ENST00000508540, ENST00000942549

RefSeq mRNA: 1 — MANE Select: NM_001267 NM_001267

CCDS: CCDS11568

Canonical transcript exons

ENST00000508540 — 4 exons

Exon	Start	End
ENSE00000737048	50465707	50465870
ENSE00001109738	50465294	50465439
ENSE00002077386	50468040	50468880
ENSE00002082736	50464496	50465049

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 97.70.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1473 / max 496.6720, expressed in 139 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166981	1.0465	126
166982	0.1008	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	97.70	gold quality
trabecular bone tissue	UBERON:0002483	89.82	gold quality
periodontal ligament	UBERON:0008266	89.65	gold quality
cerebellar hemisphere	UBERON:0002245	88.49	gold quality
cerebellar cortex	UBERON:0002129	88.33	gold quality
right lobe of liver	UBERON:0001114	88.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.27	gold quality
body of pancreas	UBERON:0001150	86.22	gold quality
cerebellum	UBERON:0002037	86.15	gold quality
calcaneal tendon	UBERON:0003701	85.82	gold quality
right adrenal gland cortex	UBERON:0035827	85.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.83	gold quality
right adrenal gland	UBERON:0001233	83.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.00	gold quality
cartilage tissue	UBERON:0002418	82.79	gold quality
mucosa of transverse colon	UBERON:0004991	82.78	gold quality
left adrenal gland	UBERON:0001234	81.98	gold quality
left adrenal gland cortex	UBERON:0035825	81.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.66	gold quality
muscle of leg	UBERON:0001383	79.89	gold quality
adrenal cortex	UBERON:0001235	79.76	gold quality
gastrocnemius	UBERON:0001388	79.70	gold quality
trachea	UBERON:0003126	79.65	gold quality
tendon	UBERON:0000043	79.27	gold quality
adrenal gland	UBERON:0002369	79.10	gold quality
caudate nucleus	UBERON:0001873	78.90	gold quality
liver	UBERON:0002107	78.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.14	gold quality
nucleus accumbens	UBERON:0001882	78.04	gold quality
putamen	UBERON:0001874	77.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting CHAD, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4729	99.69	72.18	4233

Literature-anchored findings (GeneRIF, showing 4)

• Changes in CHAD abundance or structure could be associated with the pathologic changes occurring in the scoliotic IVD. (PMID:19525844)
• chondroadherin interaction with cells may be central for maintaining the adult chondrocyte phenotype and cartilage homeostasis. (PMID:21127050)
• number of cells adhering via their beta(1) integrin receptor to collagen type II or chondroadherin was profoundly and rapidly enhanced by the addition of the heparin-binding peptide (PMID:23172228)
• crystal structures at ~2.2A resolution of human fibromodulin and chondroadherin. (PMID:28215822)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-191d15.2	ENSDARG00000092834
mus_musculus	Chad	ENSMUSG00000039084
rattus_norvegicus	Chad	ENSRNOG00000003304
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
drosophila_melanogaster	CG18095	FBGN0028872
drosophila_melanogaster	CG7509	FBGN0035575
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649
caenorhabditis_elegans		WBGENE00022789

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Chondroadherin — O15335 (reviewed: O15335)

Alternative names: Cartilage leucine-rich protein

All UniProt accessions (2): O15335, H0YA03

UniProt curated annotations — full annotation on UniProt →

Function. Promotes attachment of chondrocytes, fibroblasts, and osteoblasts. This binding is mediated (at least for chondrocytes and fibroblasts) by the integrin alpha(2)beta(1). May play an important role in the regulation of chondrocyte growth and proliferation.

Subunit / interactions. Mostly monomeric. Interacts with collagen type II.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Present in chondrocytes at all ages.

Similarity. Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily.

RefSeq proteins (1): NP_001258* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050541	LRR_TM_domain-containing	Family

Pfam: PF01462, PF13855

UniProt features (54 total): strand 15, turn 12, repeat 9, helix 6, disulfide bond 3, domain 2, sequence variant 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5LFN	X-RAY DIFFRACTION	2.1
5MX1	X-RAY DIFFRACTION	2.17

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15335-F1	93.13	0.90

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): 23–38, 304–346, 306–326

Glycosylation sites (1): 144

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GOBP_BONE_TRABECULA_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, RACCACAR_AML_Q6, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, AML_Q6, GOBP_TRABECULA_MORPHOGENESIS, MAF_Q6, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, SABATES_COLORECTAL_ADENOMA_DN, GOBP_TRABECULA_FORMATION, IK3_01, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, CAGCCTC_MIR4855P

GO Biological Process (2): bone development (GO:0060348), negative regulation of bone trabecula formation (GO:1900155)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
skeletal system development	1
animal organ development	1
negative regulation of developmental process	1
bone trabecula formation	1
regulation of bone trabecula formation	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1453 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHAD	FMOD	Q06828	601
CHAD	COMP	P49747	599
CHAD	ACAN	P16112	596
CHAD	PRELP	P51888	588
CHAD	MATN1	P21941	575
CHAD	LUM	P51884	569
CHAD	OMD	Q99983	559
CHAD	BGN	P13247	557
CHAD	CILP	O75339	517
CHAD	OGN	P20774	517
CHAD	C4A	P01028	515
CHAD	C4A	P01028	505
CHAD	COL2A1	P02458	475
CHAD	ASPN	Q9BXN1	473
CHAD	HAPLN1	P10915	457

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CHAD	CNPY4	psi-mi:“MI:0914”(association)	0.560
CHAD	CNPY4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (7): CNPY3 (Affinity Capture-MS), CNPY4 (Affinity Capture-MS), CNPY4 (Affinity Capture-MS), CNPY3 (Affinity Capture-MS), CHAD (Affinity Capture-RNA), CNPY4 (Affinity Capture-MS), CHAD (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: O02678, O15335, O35367, O42235, O46390, O46403, O46542, O55226, O60938, O62702, O70210, O75094, O94813, P07585, P19879, P20774, P21793, P21809, P21810, P28653, P28654, P28675, P47853, P51887, P51888, P82963, Q01129, Q27972, Q28888, Q29393, Q3ZBN5, Q5R1V9, Q5RBL2, Q5RI43, Q8MJF1, Q99MQ4, Q9BXN1, Q9DE65, Q9DE66, Q9DE68

Diamond homologs: A3KNN3, A4IIW9, A6NJW4, A8WHP9, E9Q7T7, O02833, O15335, O55226, O70210, O75093, O75094, O88279, O88280, O94769, O94813, P0C6S8, P24014, P35858, P35859, P56400, P58727, P70389, Q27972, Q5FW85, Q5RDJ4, Q62192, Q66HV9, Q6NUI6, Q6R5N8, Q7M6Z0, Q80TR4, Q80WD0, Q80WD1, Q86UN2, Q86UN3, Q96FE5, Q99467, Q99M75, Q99PI8, Q9BY71

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

838 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50465701:TCTTA:T	donor_loss	1.0000
17:50465702:CTTAC:C	donor_loss	1.0000
17:50465703:TTACC:T	donor_loss	1.0000
17:50465704:TA:T	donor_loss	1.0000
17:50465705:A:AC	donor_gain	1.0000
17:50465705:A:AT	donor_loss	1.0000
17:50465705:ACCG:A	donor_gain	1.0000
17:50465706:C:CC	donor_gain	1.0000
17:50465706:CCG:C	donor_gain	1.0000
17:50465706:CCGC:C	donor_gain	1.0000
17:50465738:T:TA	donor_gain	1.0000
17:50465871:C:CC	acceptor_gain	1.0000
17:50465879:CAAGG:C	acceptor_gain	1.0000
17:50468034:GCTCA:G	donor_loss	1.0000
17:50468035:CTCA:C	donor_loss	1.0000
17:50468036:TCA:T	donor_loss	1.0000
17:50468037:CA:C	donor_loss	1.0000
17:50468038:ACC:A	donor_loss	1.0000
17:50465049:CCTG:C	acceptor_loss	0.9900
17:50465050:C:CC	acceptor_gain	0.9900
17:50465051:T:A	acceptor_loss	0.9900
17:50465288:CCCCA:C	donor_loss	0.9900
17:50465289:CCCAC:C	donor_loss	0.9900
17:50465290:CCACC:C	donor_loss	0.9900
17:50465291:CAC:C	donor_loss	0.9900
17:50465292:AC:A	donor_loss	0.9900
17:50465293:C:CA	donor_loss	0.9900
17:50465294:C:G	donor_loss	0.9900
17:50465340:G:A	donor_gain	0.9900
17:50465436:CCAC:C	acceptor_gain	0.9900

AlphaMissense

2333 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50465401:C:G	C326S	0.999
17:50465402:A:T	C326S	0.999
17:50468143:A:G	L224P	0.999
17:50468431:A:G	L128P	0.999
17:50468497:A:G	L106P	0.999
17:50468503:A:C	L104W	0.999
17:50468512:A:T	L101H	0.999
17:50468513:G:A	L101F	0.999
17:50468569:A:G	L82P	0.999
17:50468575:A:G	L80S	0.999
17:50468641:A:G	L58P	0.999
17:50468647:A:G	L56P	0.999
17:50468701:C:G	C38S	0.999
17:50468701:C:T	C38Y	0.999
17:50468702:A:G	C38R	0.999
17:50468702:A:T	C38S	0.999
17:50465400:A:C	C326W	0.998
17:50465734:C:G	C304S	0.998
17:50465735:A:G	C304R	0.998
17:50465735:A:T	C304S	0.998
17:50465741:A:G	W302R	0.998
17:50465741:A:T	W302R	0.998
17:50468224:A:T	L197H	0.998
17:50468287:A:G	L176P	0.998
17:50468431:A:T	L128H	0.998
17:50468440:A:G	L125P	0.998
17:50468487:G:C	N109K	0.998
17:50468487:G:T	N109K	0.998
17:50468488:T:A	N109I	0.998
17:50468503:A:G	L104S	0.998

dbSNP variants (sampled 300 via entrez): RS1000702588 (17:50467835 G>A), RS1000776012 (17:50469192 C>T), RS1001398855 (17:50469108 G>A,C,T), RS1002850262 (17:50467405 G>T), RS1003017343 (17:50465634 T>C), RS1003046292 (17:50467676 T>C), RS1003178787 (17:50466129 C>A,T), RS1003462130 (17:50470083 C>T), RS1003741037 (17:50469863 C>G), RS1004068470 (17:50464660 G>T), RS1004463898 (17:50469792 G>A), RS1004826758 (17:50468838 T>C), RS1005853214 (17:50470790 G>T), RS1006402704 (17:50465568 T>C), RS1006463256 (17:50467110 C>T)

Disease associations

OMIM: gene MIM:602178 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_659	Blood protein levels	6.000000e-06
GCST008839_221	Height	2.000000e-25

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance	2
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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