COL28A1

Summary

COL28A1 (collagen type XXVIII alpha 1 chain, HGNC:22442) is a protein-coding gene on chromosome 7p21.3, encoding Collagen alpha-1(XXVIII) chain (Q2UY09). May act as a cell-binding protein.

COL28A1 belongs to a class of collagens containing von Willebrand factor (VWF; MIM 613160) type A (VWFA) domains (Veit et al., 2006 [PubMed 16330543]).

Source: NCBI Gene 340267 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 226 total
• Druggable target: yes
• MANE Select transcript: NM_001037763

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22442
Approved symbol	COL28A1
Name	collagen type XXVIII alpha 1 chain
Location	7p21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000215018
Ensembl biotype	protein_coding
OMIM	609996
Entrez	340267

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000399429, ENST00000430711, ENST00000435823, ENST00000444268, ENST00000453441, ENST00000465339

RefSeq mRNA: 1 — MANE Select: NM_001037763 NM_001037763

CCDS: CCDS43553

Canonical transcript exons

ENST00000399429 — 35 exons

Exon	Start	End
ENSE00001538220	7360390	7360528
ENSE00001538221	7370725	7370882
ENSE00001538223	7372998	7373546
ENSE00001538224	7375461	7375497
ENSE00001538228	7380660	7380695
ENSE00001538232	7380782	7380862
ENSE00001538243	7381544	7381612
ENSE00001538247	7417859	7417927
ENSE00001613460	7521905	7521961
ENSE00001676918	7517796	7517837
ENSE00001701085	7520062	7520115
ENSE00001757604	7532752	7532912
ENSE00001761944	7531348	7531904
ENSE00001788660	7524229	7524249
ENSE00001804117	7515814	7515840
ENSE00001817124	7357875	7358805
ENSE00001853410	7535750	7535873
ENSE00003461695	7474601	7474669
ENSE00003464806	7443585	7443653
ENSE00003473615	7477112	7477180
ENSE00003478325	7444418	7444489
ENSE00003536848	7419885	7419953
ENSE00003551502	7511091	7511135
ENSE00003571717	7440790	7440861
ENSE00003578523	7456044	7456112
ENSE00003587205	7452319	7452387
ENSE00003600737	7489389	7489457
ENSE00003620227	7506014	7506067
ENSE00003637911	7432473	7432541
ENSE00003649441	7436395	7436463
ENSE00003649603	7507117	7507161
ENSE00003662007	7432632	7432700
ENSE00003667154	7453440	7453508
ENSE00003669866	7437394	7437462
ENSE00003670445	7490578	7490646

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 98.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3279 / max 54.2742, expressed in 86 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82677	0.1900	74
82676	0.1379	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.03	gold quality
trigeminal ganglion	UBERON:0001675	95.13	gold quality
tibial nerve	UBERON:0001323	94.07	gold quality
oviduct epithelium	UBERON:0004804	93.72	gold quality
dorsal root ganglion	UBERON:0000044	93.31	gold quality
right uterine tube	UBERON:0001302	90.89	gold quality
bronchial epithelial cell	CL:0002328	87.69	gold quality
bronchus	UBERON:0002185	86.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.77	gold quality
colonic epithelium	UBERON:0000397	86.19	gold quality
parotid gland	UBERON:0001831	84.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.21	gold quality
adenohypophysis	UBERON:0002196	83.35	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.15	gold quality
lower esophagus	UBERON:0013473	82.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.85	silver quality
body of stomach	UBERON:0001161	80.63	gold quality
body of pancreas	UBERON:0001150	80.48	gold quality
fallopian tube	UBERON:0003889	80.45	gold quality
pituitary gland	UBERON:0000007	78.79	gold quality
stomach	UBERON:0000945	78.27	gold quality
epithelium of nasopharynx	UBERON:0001951	78.02	gold quality
metanephros cortex	UBERON:0010533	77.92	gold quality
fundus of stomach	UBERON:0001160	77.64	gold quality
gastrocnemius	UBERON:0001388	77.33	gold quality
muscle of leg	UBERON:0001383	76.89	gold quality
trachea	UBERON:0003126	76.19	gold quality
apex of heart	UBERON:0002098	75.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	21.48
E-ANND-3	yes	7.75
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Collagen XXVIII is a novel von Willebrand factor A domain-containing protein with many imperfections in the collagenous domain (PMID:16330543)
• COL28 promotes proliferation, migration, and EMT of renal tubular epithelial cells. (PMID:36883360)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Col28a1	ENSMUSG00000068794
rattus_norvegicus	Col28a1	ENSRNOG00000033618

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL27A1 (ENSG00000196739), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COLQ (ENSG00000206561)

Protein

Protein identifiers

Collagen alpha-1(XXVIII) chain — Q2UY09 (reviewed: Q2UY09)

All UniProt accessions (5): A0A0C4DG66, A0A0C4DG72, H7BZU0, H7C3P2, Q2UY09

UniProt curated annotations — full annotation on UniProt →

Function. May act as a cell-binding protein.

Subunit / interactions. Trimer or homomer. Secreted as a 135 kDa monomer under reducing conditions and as a homotrimer under non-reducing conditions.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Similarity. Belongs to the VWA-containing collagen family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2UY09-1	1	yes
Q2UY09-2	2
Q2UY09-3	3

RefSeq proteins (1): NP_001032852* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR002223	Kunitz_BPTI	Domain
IPR008160	Collagen	Repeat
IPR020901	Prtase_inh_Kunz-CS	Conserved_site
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR050149	Collagen_superfamily	Family

Pfam: PF00014, PF00092, PF01391

UniProt features (32 total): domain 9, sequence variant 7, compositionally biased region 5, splice variant 4, disulfide bond 3, region of interest 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2UY09-F1	61.81	0.23

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): 1072–1122, 1081–1105, 1097–1118

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 58 (showing top): GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOCC_COLLAGEN_TRIMER, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOCC_BASEMENT_MEMBRANE, GOBP_SKELETAL_SYSTEM_MORPHOGENESIS, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

GO Biological Process (1): cell adhesion (GO:0007155)

GO Molecular Function (3): serine-type endopeptidase inhibitor activity (GO:0004867), extracellular matrix structural constituent conferring tensile strength (GO:0030020), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (6): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), collagen type XXVIII trimer (GO:1990326), collagen trimer (GO:0005581), basement membrane (GO:0005604)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Collagen formation	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
extracellular matrix structural constituent	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
collagenous component of basement membrane	1
von-Willerbrand-factor-A-domain-rich collagen trimer	1
extracellular protein-containing complex	1
protein-containing complex	1
extracellular matrix	1

Protein interactions and networks

STRING

970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL28A1	VWF	P04275	566
COL28A1	FAM180A	Q6UWF9	510
COL28A1	ITGAV	P06756	404
COL28A1	ANGPTL7	O43827	403
COL28A1	ELAPOR2	A8MWY0	389
COL28A1	FAT3	Q8TDW7	384
COL28A1	CNTN6	Q9UQ52	367
COL28A1	CNIH1	O95406	353
COL28A1	CNIH3	Q8TBE1	353
COL28A1	P3H1	Q32P28	350
COL28A1	ADAMTS14	Q8WXS8	350
COL28A1	CRTAP	O75718	349
COL28A1	ANGPTL5	Q86XS5	348
COL28A1	PPP4R4	Q6NUP7	347
COL28A1	TPST1	O60507	336

IntAct

0 interactions, top by confidence:

BioGRID (4): COL28A1 (Affinity Capture-MS), COL28A1 (Affinity Capture-MS), COL28A1 (Cross-Linking-MS (XL-MS)), COL28A1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0MSJ1, A5PN28, A8WR59, B8V7R6, C0HLN2, O76368, O88207, P02462, P08122, P08125, P08572, P12106, P12107, P12108, P13942, P20849, P20850, P20908, P20909, P23206, P25067, P25318, P25940, P32017, P70560, P83371, P98085, Q03692, Q05306, Q05722, Q07092, Q07643, Q0VF58, Q14050, Q14055, Q14993, Q28083, Q28668, Q2UY09, Q2UY11

Diamond homologs: A0A1D5NSM8, A2AVA0, D3YXF5, O02839, O19124, O35764, O43405, O62685, O62837, O70340, O76536, O95502, O96530, P00751, P04003, P04186, P06205, P06206, P06207, P06681, P07629, P08174, P08607, P0C6B8, P13944, P14151, P14650, P15529, P17690, P18337, P26022, P32018, P33703, P35419, P42201, P47970, P47971, P47972, P48199, P48759

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	179
Likely benign	14
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

5652 predictions. Top by Δscore:

Variant	Effect	Δscore
7:7358806:C:CC	acceptor_gain	1.0000
7:7360524:CTCAA:C	acceptor_gain	1.0000
7:7370717:TTAC:T	donor_loss	1.0000
7:7370718:TACT:T	donor_loss	1.0000
7:7370719:A:AC	donor_gain	1.0000
7:7370719:ACTT:A	donor_loss	1.0000
7:7370720:C:CC	donor_gain	1.0000
7:7370720:CTTA:C	donor_gain	1.0000
7:7370721:TTA:T	donor_loss	1.0000
7:7370723:A:AC	donor_gain	1.0000
7:7370723:ACTG:A	donor_loss	1.0000
7:7370724:C:CA	donor_gain	1.0000
7:7370724:CT:C	donor_gain	1.0000
7:7370724:CTG:C	donor_gain	1.0000
7:7370724:CTGA:C	donor_gain	1.0000
7:7370814:C:CT	acceptor_gain	1.0000
7:7370815:A:T	acceptor_gain	1.0000
7:7370884:T:C	acceptor_gain	1.0000
7:7370884:T:TC	acceptor_gain	1.0000
7:7370886:T:C	acceptor_gain	1.0000
7:7370886:T:TC	acceptor_gain	1.0000
7:7370897:G:GC	acceptor_gain	1.0000
7:7380862:CCTT:C	acceptor_gain	1.0000
7:7435395:GGTTA:G	donor_loss	1.0000
7:7435396:GTTA:G	donor_loss	1.0000
7:7435397:TTACC:T	donor_loss	1.0000
7:7435398:TAC:T	donor_loss	1.0000
7:7435399:ACCTT:A	donor_loss	1.0000
7:7435400:CCTT:C	donor_loss	1.0000
7:7439083:ATGT:A	donor_gain	1.0000

AlphaMissense

7236 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:7358658:C:G	C1118S	0.998
7:7358659:A:T	C1118S	0.998
7:7358659:A:G	C1118R	0.995
7:7358749:A:G	W1088R	0.995
7:7358749:A:T	W1088R	0.995
7:7373491:G:C	S805R	0.995
7:7373491:G:T	S805R	0.995
7:7373493:T:G	S805R	0.995
7:7358657:A:C	C1118W	0.994
7:7358721:C:G	C1097S	0.994
7:7358722:A:T	C1097S	0.994
7:7358747:C:A	W1088C	0.994
7:7358747:C:G	W1088C	0.994
7:7373048:G:T	A953D	0.994
7:7373490:A:G	S806P	0.994
7:7373510:A:G	L799P	0.994
7:7358646:C:G	C1122S	0.993
7:7358647:A:T	C1122S	0.993
7:7358722:A:G	C1097R	0.993
7:7358675:G:C	F1112L	0.992
7:7358675:G:T	F1112L	0.992
7:7358677:A:G	F1112L	0.992
7:7373267:G:T	A880D	0.992
7:7358721:C:T	C1097Y	0.991
7:7358796:C:G	C1072S	0.991
7:7358797:A:T	C1072S	0.991
7:7358645:G:C	C1122W	0.990
7:7358647:A:G	C1122R	0.990
7:7358711:A:C	F1100L	0.990
7:7358711:A:T	F1100L	0.990

dbSNP variants (sampled 300 via entrez): RS1000011177 (7:7388905 C>G), RS1000016604 (7:7405633 A>T), RS1000025654 (7:7440403 C>T), RS1000061357 (7:7440180 A>C,G), RS1000068846 (7:7391090 T>C), RS1000082975 (7:7471550 C>T), RS1000096263 (7:7513851 A>G), RS1000103145 (7:7493909 A>C), RS1000117190 (7:7457534 T>C), RS1000120689 (7:7543704 A>T), RS1000128771 (7:7403104 A>G), RS1000145803 (7:7536096 C>T), RS1000167012 (7:7350483 T>C), RS1000180824 (7:7466125 G>A,C), RS1000192987 (7:7459696 C>G,T)

Disease associations

OMIM: gene MIM:609996 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001533_10	Immune reponse to smallpox (secreted IL-1beta)	6.000000e-08
GCST003518_32	Daytime sleep phenotypes	2.000000e-06
GCST003542_173	Night sleep phenotypes	8.000000e-06
GCST006147_2	Frontotemporal dementia (age at onset)	8.000000e-07
GCST006149_1	Frontotemporal dementia with GRN mutation (age at onset)	5.000000e-06
GCST007672_3	3-month functional outcome in ischaemic stroke (modified Rankin score)	8.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007828	daytime rest measurement
EFO:0004847	age at onset
EFO:0009603	stroke outcome severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364188 (PROTEIN COMPLEX GROUP)

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Nickel	decreases expression	2
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
Estradiol	decreases expression	1
Methamphetamine	affects response to substance	1
Paraquat	increases expression, increases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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