COL23A1

Summary

COL23A1 (collagen type XXIII alpha 1 chain, HGNC:22990) is a protein-coding gene on chromosome 5q35.3, encoding Collagen alpha-1(XXIII) chain (Q86Y22).

COL23A1 is a member of the transmembrane collagens, a subfamily of the nonfibrillar collagens that contain a single pass hydrophobic transmembrane domain (Banyard et al., 2003 [PubMed 12644459]).

Source: NCBI Gene 91522 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 125 total
• MANE Select transcript: NM_173465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22990
Approved symbol	COL23A1
Name	collagen type XXIII alpha 1 chain
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434K0621
Ensembl gene	ENSG00000050767
Ensembl biotype	protein_coding
OMIM	610043
Entrez	91522

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 nonsense_mediated_decay, 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000390654, ENST00000407622, ENST00000484750, ENST00000646779, ENST00000679888, ENST00000679896, ENST00000680268, ENST00000680889, ENST00000681261

RefSeq mRNA: 1 — MANE Select: NM_173465 NM_173465

CCDS: CCDS4436

Canonical transcript exons

ENST00000390654 — 29 exons

Exon	Start	End
ENSE00000770283	178239141	178239179
ENSE00000770284	178242042	178242128
ENSE00000973022	178249117	178249206
ENSE00000973024	178247775	178247831
ENSE00000973025	178247526	178247552
ENSE00000973026	178246391	178246453
ENSE00000973027	178246254	178246307
ENSE00000973029	178242341	178242394
ENSE00001290409	178256866	178256928
ENSE00001293360	178250061	178250105
ENSE00001295338	178248192	178248254
ENSE00001300755	178262217	178262252
ENSE00001307117	178267307	178267333
ENSE00001309173	178306875	178306919
ENSE00001323944	178257523	178257567
ENSE00001325296	178263208	178263324
ENSE00001325792	178256353	178256397
ENSE00001356640	178252544	178252597
ENSE00001356641	178254949	178255026
ENSE00001356695	178589904	178590393
ENSE00001399827	178270337	178270363
ENSE00001404070	178261722	178261748
ENSE00001407776	178268730	178268756
ENSE00001419363	178245942	178245968
ENSE00001424779	178288324	178288350
ENSE00001425372	178259721	178259747
ENSE00001508549	178237618	178238700
ENSE00002483769	178290362	178290369
ENSE00003483384	178560682	178560748

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 95.52.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8376 / max 125.4838, expressed in 404 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65176	1.3070	351
65175	0.4860	170
65174	0.0447	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	95.52	gold quality
left lobe of thyroid gland	UBERON:0001120	95.06	gold quality
thyroid gland	UBERON:0002046	94.89	gold quality
apex of heart	UBERON:0002098	86.76	gold quality
heart left ventricle	UBERON:0002084	86.01	gold quality
cardiac ventricle	UBERON:0002082	85.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.40	gold quality
mucosa of stomach	UBERON:0001199	79.91	gold quality
ileal mucosa	UBERON:0000331	79.04	gold quality
heart	UBERON:0000948	78.02	gold quality
skin of abdomen	UBERON:0001416	76.35	gold quality
right frontal lobe	UBERON:0002810	76.12	gold quality
sural nerve	UBERON:0015488	76.04	gold quality
right atrium auricular region	UBERON:0006631	75.39	gold quality
skin of leg	UBERON:0001511	75.00	gold quality
anterior cingulate cortex	UBERON:0009835	74.76	gold quality
cardiac atrium	UBERON:0002081	74.72	gold quality
tibialis anterior	UBERON:0001385	74.42	silver quality
seminal vesicle	UBERON:0000998	74.06	gold quality
zone of skin	UBERON:0000014	73.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.68	gold quality
pancreatic ductal cell	CL:0002079	73.63	silver quality
tibial nerve	UBERON:0001323	73.21	gold quality
metanephros cortex	UBERON:0010533	72.88	gold quality
right lung	UBERON:0002167	72.86	gold quality
prefrontal cortex	UBERON:0000451	72.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.82	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting COL23A1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3941	99.86	70.54	2735
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4292	99.16	65.57	1767

Literature-anchored findings (GeneRIF, showing 5)

• identification and cloning; a new member of the transmembrane collagen family, showing structural homology with the transmembrane collagens XIII and XXV (PMID:12644459)
• analysis of collagen XXIII mRNA and protein (PMID:16728390)
• newly synthesized collagen XXIII either is cleaved inside the Golgi/trans-Golgi network or reaches the cell surface, where it becomes protected from processing by being localized in lipid rafts. (PMID:17627939)
• High COL23A1 expression is associated with recurrent non-small cell lung cancer. (PMID:20447926)
• data suggest that extracellular membrane-bound CAIV, but not cytosolic CAII, augments transport activity of MCT2 in a non-catalytic manner, possibly by facilitating a proton pathway other than His-88 (PMID:21652699)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	col7a1l	ENSDARG00000069692
danio_rerio	si:dkey-117n7.4	ENSDARG00000092064
		ENSDARG00000105274
mus_musculus	Col23a1	ENSMUSG00000063564
rattus_norvegicus	Col23a1	ENSRNOG00000003349

Paralogs (37): COL9A2 (ENSG00000049089), 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), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Collagen alpha-1(XXIII) chain — Q86Y22 (reviewed: Q86Y22)

All UniProt accessions (5): A0A0A0MSD3, A0A2R8Y887, A0A7P0T8B8, Q86Y22, L8EAS4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homotrimer.

Subcellular location. Cell membrane.

Post-translational modifications. Undergoes proteolytic cleavage by furin protease to yield a 60 kDa soluble form that forms a homotrimer and exhibits a low affinity interaction with heparin.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86Y22-1	1	yes
Q86Y22-2	2

RefSeq proteins (1): NP_775736* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008160	Collagen	Repeat
IPR050938	Collagen_Structural_Proteins	Family

Pfam: PF01391

UniProt features (27 total): compositionally biased region 9, splice variant 5, domain 5, region of interest 3, topological domain 2, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86Y22-F1	59.01	0.05

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-216083	Integrin cell surface interactions
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 82 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOCC_COLLAGEN_TRIMER, GOCC_CELL_SURFACE, SRF_Q5_01, AAACCAC_MIR140, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, GOMF_GLYCOSAMINOGLYCAN_BINDING, OCT1_B, CCCNNGGGAR_OLF1_01, GOMF_HEPARIN_BINDING, REACTOME_INTEGRIN_CELL_SURFACE_INTERACTIONS, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOMF_SULFUR_COMPOUND_BINDING

GO Biological Process (0):

GO Molecular Function (4): heparin binding (GO:0008201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular matrix (GO:0031012), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Degradation of the extracellular matrix	1
Collagen formation	1
Extracellular matrix organization	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
glycosaminoglycan binding	1
sulfur compound binding	1
extracellular matrix structural constituent	1
protein binding	1
binding	1
protein-containing complex	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
external encapsulating structure	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL23A1	FURIN	P09958	568
COL23A1	C2CD4D	B7Z1M9	480
COL23A1	MMP9	P14780	451
COL23A1	COL26A1	Q96A83	438
COL23A1	SLC16A2	P36021	428
COL23A1	PHYKPL	Q8IUZ5	404
COL23A1	TMEM184C	Q9NVA4	400
COL23A1	SPATA17	Q96L03	378
COL23A1	CPLX3	Q8WVH0	337
COL23A1	COL8A1	P27658	332
COL23A1	PCOLCE2	Q9UKZ9	332
COL23A1	COL25A1	Q9BXS0	318
COL23A1	LAMB3	Q13751	311
COL23A1	ANKS1B	Q7Z6G8	302
COL23A1	ANKFY1	Q9P2R3	300

IntAct

12 interactions, top by confidence:

A	B	Type	Score
EXOSC8	COL23A1	psi-mi:“MI:0915”(physical association)	0.560
COL23A1	EXOSC8	psi-mi:“MI:0915”(physical association)	0.560
COL23A1	RPL10A	psi-mi:“MI:0915”(physical association)	0.400
COL23A1	SYNE2	psi-mi:“MI:0915”(physical association)	0.400
COL23A1	H4C16	psi-mi:“MI:0915”(physical association)	0.400
COL23A1	H1-4	psi-mi:“MI:0915”(physical association)	0.400
COL23A1	LMNA	psi-mi:“MI:0915”(physical association)	0.400
COL23A1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
COL23A1	PLOD2	psi-mi:“MI:0914”(association)	0.350
LSM8	COL23A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): COL23A1 (Two-hybrid), COL23A1 (Affinity Capture-RNA), COL23A1 (Proximity Label-MS), SYNE2 (Proximity Label-MS), COL23A1 (Proximity Label-MS), COL23A1 (Proximity Label-MS), COL23A1 (Proximity Label-MS), COL23A1 (Two-hybrid), PLOD2 (Affinity Capture-MS), PLOD1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), PLOD3 (Affinity Capture-MS), COL23A1 (PCA), COL23A1 (Co-fractionation), COL23A1 (Co-fractionation)

ESM2 similar proteins: C0HLH0, C0HLH4, C0HLI6, C0HLN2, P02460, P02462, P02463, P05997, P08120, P08122, P08125, P08572, P12106, P12107, P12108, P13942, P20849, P20850, P20909, P23206, P25318, P27393, P29400, P30754, P32017, P70560, Q01955, Q03692, Q05306, Q05722, Q07643, Q0VF58, Q14031, Q14050, Q14055, Q14993, Q28083, Q28247, Q32S24, Q3U962

Diamond homologs: Q810Y4, Q86Y22, Q8K4G2, Q99MQ5, Q9BXS0, Q9R1N9, Q5TAT6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

8041 predictions. Top by Δscore:

Variant	Effect	Δscore
5:178239127:T:TA	donor_gain	1.0000
5:178239128:C:A	donor_gain	1.0000
5:178246389:A:AC	donor_gain	1.0000
5:178246390:C:CC	donor_gain	1.0000
5:178248191:CCAGG:C	donor_gain	1.0000
5:178248199:T:A	donor_gain	1.0000
5:178256804:C:CA	donor_gain	1.0000
5:178261718:TCA:T	donor_loss	1.0000
5:178261719:CACCT:C	donor_loss	1.0000
5:178261750:T:A	acceptor_loss	1.0000
5:178263202:TCTTA:T	donor_loss	1.0000
5:178263203:CTTAC:C	donor_loss	1.0000
5:178263204:TTACC:T	donor_loss	1.0000
5:178263205:TA:T	donor_loss	1.0000
5:178263206:A:AC	donor_gain	1.0000
5:178263207:C:CC	donor_gain	1.0000
5:178263207:CCG:C	donor_gain	1.0000
5:178270335:A:AC	donor_gain	1.0000
5:178270336:C:CC	donor_gain	1.0000
5:178270336:CGGG:C	donor_gain	1.0000
5:178238606:CCA:C	acceptor_gain	0.9900
5:178238607:C:CT	acceptor_gain	0.9900
5:178238607:C:T	acceptor_gain	0.9900
5:178238608:A:AC	acceptor_gain	0.9900
5:178238608:A:C	acceptor_gain	0.9900
5:178238699:CA:C	acceptor_gain	0.9900
5:178238701:C:CC	acceptor_gain	0.9900
5:178239138:TA:T	donor_loss	0.9900
5:178239139:ACC:A	donor_loss	0.9900
5:178239140:CCTTA:C	donor_loss	0.9900

AlphaMissense

3345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:178242050:A:G	C525R	0.996
5:178242049:C:G	C525S	0.994
5:178242049:C:T	C525Y	0.994
5:178242050:A:T	C525S	0.994
5:178239152:A:G	C537R	0.993
5:178239151:C:G	C537S	0.992
5:178239152:A:T	C537S	0.992
5:178242048:A:C	C525W	0.992
5:178246279:C:T	G463E	0.990
5:178263251:C:T	G199D	0.990
5:178270362:C:T	G148E	0.990
5:178290369:C:T	G136D	0.990
5:178306901:C:T	G127D	0.990
5:178239151:C:T	C537Y	0.988
5:178242109:C:T	G505D	0.988
5:178242393:C:T	G481D	0.988
5:178288331:C:T	G145D	0.988
5:178306892:C:T	G130E	0.988
5:178246270:C:T	G466E	0.987
5:178288340:C:T	G142E	0.987
5:178306883:C:T	G133D	0.987
5:178239150:G:C	C537W	0.986
5:178263233:C:T	G205D	0.986
5:178288349:C:T	G139E	0.985
5:178263260:C:T	G196D	0.984
5:178306910:C:T	G124E	0.984
5:178242049:C:A	C525F	0.983
5:178242101:C:G	G508R	0.983
5:178242101:C:T	G508R	0.983
5:178263242:C:T	G202E	0.982

dbSNP variants (sampled 300 via entrez): RS1000006999 (5:178366215 C>T), RS1000010297 (5:178455080 A>C), RS1000022030 (5:178561888 G>A), RS1000031708 (5:178328348 G>A,C), RS1000041509 (5:178355224 T>C), RS1000042797 (5:178476197 G>A), RS1000044695 (5:178532717 C>T), RS1000050207 (5:178285112 G>C), RS1000062309 (5:178292672 T>C,G), RS1000070475 (5:178417822 C>T), RS1000071684 (5:178465713 C>T), RS1000074115 (5:178355371 C>G), RS1000092318 (5:178587992 A>C,G,T), RS1000138917 (5:178379061 G>A,T), RS1000150563 (5:178449892 C>T)

Disease associations

OMIM: gene MIM:610043 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001762_247	Obesity-related traits	6.000000e-06
GCST001958_7	Bulimia nervosa	6.000000e-06
GCST003465_17	Cannabis dependence symptom count	2.000000e-07
GCST003563_10	Presence of antiphospholipid antibodies	3.000000e-06
GCST006085_81	Prostate cancer	7.000000e-09
GCST006499_1	Nose length	3.000000e-10
GCST006585_2990	Blood protein levels	4.000000e-07
GCST012320_1	HDL levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement
EFO:0008457	cannabis dependence measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Air Pollutants	affects methylation	1
Arsenic	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	affects methylation	1
Rotenone	increases expression	1
Dronabinol	decreases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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