CHADL

Summary

CHADL (chondroadherin like, HGNC:25165) is a protein-coding gene on chromosome 22q13.2, encoding Chondroadherin-like protein (Q6NUI6). Potential negative modulator of chondrocyte differentiation.

Enables collagen binding activity and collagen fibril binding activity. Involved in negative regulation of collagen fibril organization. Located in collagen-containing extracellular matrix.

Source: NCBI Gene 150356 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 174 total — 1 pathogenic
• MANE Select transcript: NM_138481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25165
Approved symbol	CHADL
Name	chondroadherin like
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	SLRR4B
Ensembl gene	ENSG00000100399
Ensembl biotype	protein_coding
OMIM	616236
Entrez	150356

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000216241, ENST00000417999, ENST00000455425, ENST00000892870, ENST00000892871

RefSeq mRNA: 1 — MANE Select: NM_138481 NM_138481

CCDS: CCDS46715

Canonical transcript exons

ENST00000216241 — 6 exons

Exon	Start	End
ENSE00000880446	41235145	41235343
ENSE00001176939	41236484	41236650
ENSE00001202585	41239443	41239620
ENSE00001424674	41237176	41238885
ENSE00001658563	41229513	41229730
ENSE00001870639	41240874	41240931

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5243 / max 379.9191, expressed in 109 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194345	1.2577	99
194346	0.2050	77
194348	0.0407	23
194347	0.0209	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	96.74	gold quality
spinal cord	UBERON:0002240	95.04	gold quality
tibia	UBERON:0000979	89.87	gold quality
corpus callosum	UBERON:0002336	89.75	gold quality
medial globus pallidus	UBERON:0002477	89.29	silver quality
endothelial cell	CL:0000115	88.88	silver quality
apex of heart	UBERON:0002098	88.83	gold quality
substantia nigra	UBERON:0002038	87.35	gold quality
cartilage tissue	UBERON:0002418	86.14	gold quality
hypothalamus	UBERON:0001898	85.92	gold quality
putamen	UBERON:0001874	85.44	gold quality
midbrain	UBERON:0001891	85.32	gold quality
globus pallidus	UBERON:0001875	85.04	silver quality
Brodmann (1909) area 9	UBERON:0013540	84.58	gold quality
caudate nucleus	UBERON:0001873	84.21	gold quality
nucleus accumbens	UBERON:0001882	83.58	gold quality
prefrontal cortex	UBERON:0000451	83.37	gold quality
amygdala	UBERON:0001876	83.36	gold quality
right atrium auricular region	UBERON:0006631	82.39	gold quality
right frontal lobe	UBERON:0002810	81.82	gold quality
peripheral nervous system	UBERON:0000010	81.59	gold quality
tibial nerve	UBERON:0001323	81.59	gold quality
cardiac atrium	UBERON:0002081	81.32	gold quality
anterior cingulate cortex	UBERON:0009835	81.09	gold quality
inferior vagus X ganglion	UBERON:0005363	80.95	gold quality
sural nerve	UBERON:0015488	80.77	gold quality
heart left ventricle	UBERON:0002084	80.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.80	gold quality
cardiac ventricle	UBERON:0002082	79.10	gold quality
Ammon’s horn	UBERON:0001954	78.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.36
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting CHADL, 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-6124	99.87	69.78	3551
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4524B-3P	95.52	64.12	964
HSA-MIR-7108-3P	94.37	64.79	183

Literature-anchored findings (GeneRIF, showing 2)

• CHADL appears to have a negative regulatory role, possibly ensuring the formation of a stable extracellular matrix. (PMID:25451920)
• Data show that a rare missense variant in the COMP gene (cartilage oligomeric matrix protein) and a frameshift variant in the CHADL gene (chondroadherin-like protein) strongly associate with osteoarthritis total hip replacement. (PMID:28319091)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-191d15.2	ENSDARG00000092834
mus_musculus	Chadl	ENSMUSG00000063765
rattus_norvegicus	Chadl	ENSRNOG00000024631
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): LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), 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-like protein — Q6NUI6 (reviewed: Q6NUI6)

All UniProt accessions (3): Q6NUI6, B0QYT2, H0Y4I5

UniProt curated annotations — full annotation on UniProt →

Function. Potential negative modulator of chondrocyte differentiation. Inhibits collagen fibrillogenesis in vitro. May influence chondrocyte’s differentiation by acting on its cellular collagenous microenvironment.

Subunit / interactions. Associates with collagen and binds to collagen fibrils.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NUI6-1	1	yes
Q6NUI6-2	2

RefSeq proteins (1): NP_612490* (*=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: PF13855

UniProt features (44 total): repeat 19, sequence conflict 7, domain 4, disulfide bond 3, region of interest 2, compositionally biased region 2, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUI6-F1	84.58	0.60

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): 396–411, 679–722, 681–701

Glycosylation sites (2): 52, 626

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_CHONDROCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_CHONDROCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT

GO Biological Process (2): negative regulation of chondrocyte differentiation (GO:0032331), negative regulation of collagen fibril organization (GO:1904027)

GO Molecular Function (5): collagen binding (GO:0005518), extracellular matrix structural constituent conferring compression resistance (GO:0030021), signaling receptor activity (GO:0038023), collagen fibril binding (GO:0098633), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
negative regulation of cell differentiation	1
negative regulation of cartilage development	1
collagen fibril organization	1
negative regulation of extracellular matrix organization	1
regulation of collagen fibril organization	1
protein-containing complex binding	1
extracellular matrix structural constituent	1
molecular transducer activity	1
extracellular matrix binding	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHADL	BCL2L14	Q9BZR8	427
CHADL	P3H2	Q8IVL5	410
CHADL	HOMER3	Q9NSC5	407
CHADL	L3MBTL2	Q969R5	397
CHADL	CHST12	Q9NRB3	384
CHADL	A0A494C1N4	A0A494C1N4	367
CHADL	SHISA8	B8ZZ34	366
CHADL	DCAF4L1	Q3SXM0	349
CHADL	STK32A	Q8WU08	346
CHADL	EPYC	Q99645	341
CHADL	GFM2	Q969S9	338
CHADL	RSRC1	Q96IZ7	328
CHADL	PHETA2	Q6ICB4	322
CHADL	THOC2	Q8NI27	314
CHADL	XKR6	Q5GH73	310

IntAct

0 interactions, top by confidence:

BioGRID (3): CHADL (Affinity Capture-RNA), RAC1 (Cross-Linking-MS (XL-MS)), HSP90AB1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2A9Q0, A5PKD8, B0BNK7, D2HFT7, D4ABX8, E9Q7T7, O75325, O94819, P0C7J6, P0DKB5, Q04785, Q13641, Q1RMS4, Q24JP5, Q28730, Q2I0M4, Q2WF71, Q460M5, Q4R8Y9, Q50LG9, Q5PQV5, Q6NUI6, Q6PJG9, Q6UKI2, Q7M6Z0, Q80TG9, Q80W15, Q80WD1, Q80XU8, Q86UN3, Q86WK7, Q8BHA1, Q8BLY3, Q8BNW9, Q8C013, Q8WX77, Q96PE1, Q9BE71, Q9BTN0, Q9BY71

Diamond homologs: A3KNN3, A4IIW9, A6H789, A6H793, A6NJW4, A8WHP9, E9Q7T7, O46379, O75093, O75094, O88280, O94769, P21793, P24014, P51884, P51885, P51886, P59034, P59035, P83503, Q05443, Q3MHH9, Q5FW85, Q5M7S9, Q65YW8, Q6EMK4, Q6NUI6, Q6R5N8, Q8R5M3, Q8VCH9, Q96PB8, Q9BY71, Q9GKQ6, Q9GZU5, Q9TTE2, Q9WVB4, Q9WVC1, Q9Z0L0, A0N0X6, A1KZ92

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	158
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062461	GRCh37/hg19 22q13.2(chr22:41430641-41815625)x1	Pathogenic

SpliceAI

1150 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41229625:G:GT	donor_gain	1.0000
22:41229653:GAGA:G	donor_gain	1.0000
22:41229655:GA:G	donor_gain	1.0000
22:41229657:G:GG	donor_gain	1.0000
22:41230137:A:AG	acceptor_gain	1.0000
22:41230138:G:GG	acceptor_gain	1.0000
22:41230138:GTC:G	acceptor_gain	1.0000
22:41230138:GTCA:G	acceptor_gain	1.0000
22:41236479:CCCA:C	donor_loss	1.0000
22:41236480:CCA:C	donor_loss	1.0000
22:41236481:CA:C	donor_loss	1.0000
22:41236482:A:AT	donor_loss	1.0000
22:41238886:C:CC	acceptor_gain	1.0000
22:41229532:A:AG	acceptor_gain	0.9900
22:41229536:AAAG:A	acceptor_gain	0.9900
22:41229536:AAAGG:A	acceptor_gain	0.9900
22:41229537:AAG:A	acceptor_gain	0.9900
22:41229538:A:G	acceptor_gain	0.9900
22:41229538:AG:A	acceptor_gain	0.9900
22:41229538:AGGGA:A	acceptor_loss	0.9900
22:41229539:GG:G	acceptor_gain	0.9900
22:41229654:A:T	donor_gain	0.9900
22:41229683:C:T	donor_gain	0.9900
22:41230134:TTCA:T	acceptor_loss	0.9900
22:41230135:TCAGT:T	acceptor_loss	0.9900
22:41230136:CA:C	acceptor_loss	0.9900
22:41230137:AG:A	acceptor_loss	0.9900
22:41230138:G:A	acceptor_loss	0.9900
22:41230138:GT:G	acceptor_gain	0.9900
22:41230138:GTCAT:G	acceptor_gain	0.9900

AlphaMissense

4769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41238425:T:A	N216I	0.992
22:41238755:A:G	F106S	0.992
22:41238496:G:C	N192K	0.991
22:41238496:G:T	N192K	0.991
22:41238827:A:C	F82C	0.991
22:41238352:G:C	N240K	0.990
22:41238352:G:T	N240K	0.990
22:41238827:A:G	F82S	0.990
22:41238424:G:C	N216K	0.988
22:41238424:G:T	N216K	0.988
22:41238426:T:A	N216Y	0.988
22:41238568:G:C	N168K	0.988
22:41238568:G:T	N168K	0.988
22:41238640:G:C	N144K	0.988
22:41238640:G:T	N144K	0.988
22:41238497:T:A	N192I	0.986
22:41238728:A:T	L115H	0.986
22:41238856:A:C	N72K	0.986
22:41238856:A:T	N72K	0.986
22:41237804:A:G	F423S	0.985
22:41238755:A:C	F106C	0.985
22:41238784:G:C	C96W	0.985
22:41238809:A:T	L88H	0.985
22:41238866:A:G	L69P	0.985
22:41237804:A:C	F423C	0.984
22:41238498:T:A	N192Y	0.984
22:41238570:T:A	N168Y	0.984
22:41238785:C:T	C96Y	0.984
22:41238800:A:G	L91P	0.984
22:41239486:C:G	C48S	0.984

dbSNP variants (sampled 300 via entrez): RS1000054281 (22:41241667 G>C), RS1000070747 (22:41235482 C>A,T), RS1000363070 (22:41241378 G>A), RS1000464149 (22:41242261 TTATA>T), RS1000516560 (22:41237880 G>A,C,T), RS1001256261 (22:41236162 A>C), RS1001290357 (22:41235911 G>A), RS1001462700 (22:41241076 C>T), RS1001800695 (22:41241790 G>A), RS1001828533 (22:41235232 C>T), RS1001965687 (22:41230662 T>C,G), RS1002066093 (22:41235408 G>A), RS1002926141 (22:41239791 C>A,T), RS1003018607 (22:41234236 A>G), RS1003517984 (22:41238386 G>C,T)

Disease associations

OMIM: gene MIM:616236 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002539_94	Schizophrenia	2.000000e-11
GCST003043_197	Inflammatory bowel disease	3.000000e-06
GCST003044_35	Crohn’s disease	2.000000e-10
GCST004017_2	Neuroticism	9.000000e-09
GCST004199_1	Osteoarthritis (with total hip replacement)	5.000000e-18
GCST004521_55	Autism spectrum disorder or schizophrenia	9.000000e-09
GCST005232_52	Neuroticism	3.000000e-18
GCST005839_22	Depression	8.000000e-09
GCST006803_24	Schizophrenia	6.000000e-13
GCST006926_19	Osteoarthritis (hip)	2.000000e-25
GCST006950_3	Feeling worry	2.000000e-08
GCST009600_38	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	5.000000e-14
GCST010002_83	Refractive error	2.000000e-27
GCST010133_13	Lamb consumption	3.000000e-08
GCST011126_37	Caffeine consumption from coffee or tea	1.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0007942	hip osteoarthritis symptom severity measurement
EFO:0009589	worry measurement
EFO:0008111	diet measurement
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
sodium arsenite	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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