COL14A1

Summary

COL14A1 (collagen type XIV alpha 1 chain, HGNC:2191) is a protein-coding gene on chromosome 8q24.12, encoding Collagen alpha-1(XIV) chain (Q05707). Plays an adhesive role by integrating collagen bundles.

This gene encodes the alpha chain of type XIV collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XIV collagen interacts with the fibril surface and is involved in the regulation of fibrillogenesis.

Source: NCBI Gene 7373 — RefSeq curated summary.

At a glance

• Gene–disease (curated): punctate palmoplantar keratoderma type 1 (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 379 total
• Phenotypes (HPO): 25
• Druggable target: yes
• MANE Select transcript: NM_021110

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2191
Approved symbol	COL14A1
Name	collagen type XIV alpha 1 chain
Location	8q24.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187955
Ensembl biotype	protein_coding
OMIM	120324
Entrez	7373

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000297848, ENST00000309791, ENST00000432943, ENST00000434620, ENST00000440844, ENST00000498051, ENST00000523142, ENST00000537875, ENST00000964662, ENST00000964663, ENST00000964664

RefSeq mRNA: 13 — MANE Select: NM_021110 NM_001384947, NM_001413490, NM_001413491, NM_001413492, NM_001413493, NM_001413494, NM_001413495, NM_001413496, NM_001413497, NM_001413498, NM_001413499, NM_001413500, NM_021110

CCDS: CCDS34938, CCDS94338

Canonical transcript exons

ENST00000297848 — 48 exons

Exon	Start	End
ENSE00000702890	120278111	120278234
ENSE00000702891	120278435	120278578
ENSE00000702894	120279935	120280099
ENSE00000702896	120280711	120280749
ENSE00000702898	120280921	120281059
ENSE00000702899	120283636	120283778
ENSE00000702901	120285861	120285970
ENSE00000702903	120289608	120289766
ENSE00000702905	120297511	120297588
ENSE00000702907	120300732	120300818
ENSE00000702910	120310009	120310062
ENSE00000702912	120313932	120314027
ENSE00000702914	120315533	120315586
ENSE00000702916	120315944	120315997
ENSE00000702917	120332141	120332194
ENSE00000702919	120332664	120332735
ENSE00001137193	120367171	120367248
ENSE00001137198	120345375	120345563
ENSE00001137202	120342380	120342446
ENSE00001137208	120341325	120341360
ENSE00001157957	120369330	120369485
ENSE00001896910	120371152	120373573
ENSE00003478957	120158130	120158246
ENSE00003480662	120199402	120199566
ENSE00003481426	120212448	120212577
ENSE00003484236	120255240	120255356
ENSE00003485290	120266827	120266883
ENSE00003491919	120197811	120197930
ENSE00003500672	120225088	120225214
ENSE00003519973	120247613	120247735
ENSE00003537350	120231467	120231618
ENSE00003557380	120162426	120162569
ENSE00003557787	120270035	120270174
ENSE00003562018	120196791	120196946
ENSE00003569905	120209756	120209901
ENSE00003590313	120168161	120168247
ENSE00003592188	120203709	120203870
ENSE00003596710	120147806	120147930
ENSE00003604219	120226627	120226766
ENSE00003608173	120250617	120250766
ENSE00003610746	120206943	120207094
ENSE00003614050	120262868	120263014
ENSE00003651920	120216351	120216490
ENSE00003658024	120208232	120208361
ENSE00003661095	120243879	120244008
ENSE00003672149	120227220	120227352
ENSE00003688699	120228710	120228769
ENSE00003845457	120125102	120125340

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 99.41.

FANTOM5 (CAGE): breadth broad, TPM avg 19.9403 / max 1180.7840, expressed in 760 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90416	12.8100	644
90417	6.0152	597
90419	0.4730	183
90420	0.2571	131
90418	0.2512	98
205303	0.0839	44
90415	0.0500	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	99.41	gold quality
right coronary artery	UBERON:0001625	99.21	gold quality
popliteal artery	UBERON:0002250	99.18	gold quality
tibial artery	UBERON:0007610	99.18	gold quality
aorta	UBERON:0000947	99.15	gold quality
thoracic aorta	UBERON:0001515	99.15	gold quality
cartilage tissue	UBERON:0002418	99.14	gold quality
ascending aorta	UBERON:0001496	99.12	gold quality
artery	UBERON:0001637	99.05	gold quality
gall bladder	UBERON:0002110	98.72	gold quality
left coronary artery	UBERON:0001626	98.40	gold quality
saphenous vein	UBERON:0007318	98.35	gold quality
coronary artery	UBERON:0001621	98.28	gold quality
blood vessel layer	UBERON:0004797	97.76	gold quality
calcaneal tendon	UBERON:0003701	97.20	gold quality
vena cava	UBERON:0004087	97.04	gold quality
superficial temporal artery	UBERON:0001614	96.64	gold quality
mammalian vulva	UBERON:0000997	96.48	gold quality
tendon of biceps brachii	UBERON:0008188	96.42	gold quality
synovial joint	UBERON:0002217	96.25	gold quality
tendon	UBERON:0000043	96.24	gold quality
colonic epithelium	UBERON:0000397	95.78	gold quality
ectocervix	UBERON:0012249	95.47	gold quality
smooth muscle tissue	UBERON:0001135	95.35	gold quality
right ovary	UBERON:0002118	95.27	gold quality
mucosa of urinary bladder	UBERON:0001259	95.26	gold quality
left ovary	UBERON:0002119	95.07	gold quality
endocervix	UBERON:0000458	94.96	gold quality
skin of hip	UBERON:0001554	94.82	gold quality
mammary duct	UBERON:0001765	94.78	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	7105.12
E-MTAB-8322	yes	1738.49
E-MTAB-10662	yes	737.37
E-MTAB-9906	yes	667.41
E-MTAB-6701	yes	67.33
E-MTAB-8410	yes	59.95
E-HCAD-10	yes	35.68
E-ANND-3	yes	21.72
E-HCAD-1	yes	18.58
E-MTAB-10287	yes	15.51
E-CURD-112	yes	10.92
E-GEOD-130148	yes	6.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting COL14A1, 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-4682	100.00	68.89	1258
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 6)

• Results suggest that collagens XII and XIV might serve different functions during human embryonic development although their structures are highly similar. (PMID:15609093)
• the fibronectin type III domain of collagen XIV is an inducer of quiescence and differentiation in fibroblasts and preadipocytes (PMID:16129687)
• The aim of this study was therefore to test the association between polymorphisms within COL12A1 and COL14A1 and Achilles tendon injuries (PMID:17960519)
• In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. (PMID:22573329)
• COL14A1 would be a casual gene for punctate palmoplantar keratoderma. (PMID:22972947)
• the intima+media of IPAH vessels, collagens (COL4A5, COL14A1, and COL18A1), matrix metalloproteinase (MMP) 19, and a disintegrin and metalloprotease (ADAM) 33 were higher expressed, whereas MMP10, ADAM17, TIMP1, and TIMP3 were less abundant. (PMID:25840998)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	col14a1a	ENSDARG00000005762
danio_rerio	col14a1b	ENSDARG00000076623
mus_musculus	Col14a1	ENSMUSG00000022371
rattus_norvegicus	Col14a1	ENSRNOG00000026415

Paralogs (12): COCH (ENSG00000100473), COL12A1 (ENSG00000111799), MATN4 (ENSG00000124159), MATN3 (ENSG00000132031), MATN2 (ENSG00000132561), MATN1 (ENSG00000162510), COL6A3 (ENSG00000163359), VWA2 (ENSG00000165816), COL6A5 (ENSG00000172752), VWA1 (ENSG00000179403), VIT (ENSG00000205221), COL6A6 (ENSG00000206384)

Protein

Protein identifiers

Collagen alpha-1(XIV) chain — Q05707 (reviewed: Q05707)

Alternative names: Undulin

All UniProt accessions (5): Q05707, H0YBB2, J3QT75, J3QT83, Q4G0W3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an adhesive role by integrating collagen bundles. It is probably associated with the surface of interstitial collagen fibrils via COL1. The COL2 domain may then serve as a rigid arm which sticks out from the fibril and protrudes the large N-terminal globular domain into the extracellular space, where it might interact with other matrix molecules or cell surface receptors.

Subunit / interactions. Homotrimer.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in all cases and bind carbohydrates. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. May contain numerous cysteine residues involved in inter- and intramolecular disulfide bonding.

Similarity. Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q05707-1	1, Undulin 1, Un1	yes
Q05707-2	2
Q05707-3	3, Undulin 2, Un2

RefSeq proteins (13): NP_001371876, NP_001400419, NP_001400420, NP_001400421, NP_001400422, NP_001400423, NP_001400424, NP_001400425, NP_001400426, NP_001400427, NP_001400428, NP_001400429, NP_066933* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR003961	FN3_dom	Domain
IPR008160	Collagen	Repeat
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR048287	TSPN-like_N	Domain
IPR050525	ECM_Assembly_Org	Family

Pfam: PF00041, PF00092, PF01391

UniProt features (97 total): modified residue 46, domain 15, glycosylation site 12, region of interest 6, compositionally biased region 6, sequence variant 5, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05707-F1	74.06	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.

Post-translational modifications (46): 1467, 1470, 1476, 1482, 1485, 1497, 1503, 1517, 1520, 1523, 1526, 1532, 1538, 1544, 1550, 1556, 1565, 1568, 1574, 1577 …

Glycosylation sites (12): 94, 137, 372, 1384, 1388, 1476, 1485, 1523, 1526, 1601, 1698, 1701

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-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 318 (showing top): MORF_ITGA2, ACTACCT_MIR196A_MIR196B, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOCC_COLLAGEN_TRIMER, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, MORF_RAD51L3, GCM_PRKCG, GOBP_CELL_CELL_ADHESION, GCM_RING1, GOBP_VENTRICULAR_CARDIAC_MUSCLE_TISSUE_DEVELOPMENT

GO Biological Process (7): ventricular cardiac muscle tissue development (GO:0003229), extracellular matrix organization (GO:0030198), collagen fibril organization (GO:0030199), homeostasis of number of cells within a tissue (GO:0048873), regulation of cell growth involved in cardiac muscle cell development (GO:0061050), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (6): RNA binding (GO:0003723), extracellular matrix structural constituent (GO:0005201), collagen binding (GO:0005518), extracellular matrix structural constituent conferring tensile strength (GO:0030020), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), collagen trimer (GO:0005581), collagen type XIV trimer (GO:0005596), interstitial matrix (GO:0005614), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Collagen formation	2
Degradation of the extracellular matrix	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular matrix	2
cardiac muscle tissue development	1
extracellular structure organization	1
external encapsulating structure organization	1
extracellular matrix organization	1
tissue homeostasis	1
homeostasis of number of cells	1
regulation of cell growth	1
regulation of cardiac muscle tissue growth	1
cell growth involved in cardiac muscle cell development	1
cell adhesion	1
cellular process	1
nucleic acid binding	1
structural molecule activity	1
protein-containing complex binding	1
extracellular matrix structural constituent	1
protein binding	1
molecular adaptor activity	1
binding	1
cellular anatomical structure	1
protein-containing complex	1
FACIT collagen trimer	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

1790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL14A1	DCN	P07585	882
COL14A1	FN1	P02751	718
COL14A1	ELN	P15502	715
COL14A1	LUM	P51884	623
COL14A1	CTNND1	O60716	612
COL14A1	LAMC1	P11047	609
COL14A1	COL5A1	P20908	584
COL14A1	ASPN	Q9BXN1	584
COL14A1	LAMB1	P07942	581
COL14A1	MFAP4	P55083	576
COL14A1	ICAM1	P05362	574
COL14A1	COL15A1	P39059	559
COL14A1	ITGA8	P53708	539
COL14A1	TGFB3	P10600	536
COL14A1	COL1A2	P02464	534

IntAct

74 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
MMP9	TIMP1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
PRELP	AMD1	psi-mi:“MI:0914”(association)	0.530
CNPY3	SELENOT	psi-mi:“MI:0914”(association)	0.530
PRDX2	PRDX3	psi-mi:“MI:0914”(association)	0.510
SYCN	AIP	psi-mi:“MI:0914”(association)	0.500
COL14A1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
COL14A1	HDAC2	psi-mi:“MI:0915”(physical association)	0.400
SCGB1D2	COL14A1	psi-mi:“MI:0915”(physical association)	0.400
TIMP4	COL14A1	psi-mi:“MI:0915”(physical association)	0.400
CD81	HIP1R	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
NAGA	TMEM223	psi-mi:“MI:0914”(association)	0.350
OS9	GXYLT2	psi-mi:“MI:0914”(association)	0.350
RNASE13	POTEF	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
P4HA2	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
FCN3	METTL15	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
RLN2	AIP	psi-mi:“MI:0914”(association)	0.350
P4HA1	POLRMT	psi-mi:“MI:0914”(association)	0.350
FGL1	DNM1L	psi-mi:“MI:0914”(association)	0.350
PLOD1	PLK4	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS)

ESM2 similar proteins: A2A8L5, A4IFW2, A7MBJ4, B0V2N1, F1NWE3, G5EF96, O00533, O42414, O55005, O89026, O94856, O97394, P10586, P11627, P16621, P20241, P23468, P28685, P32004, P35331, P70232, P97685, P97686, Q02246, Q05695, Q05707, Q13332, Q2EY14, Q2EY15, Q2VWP7, Q2VWP9, Q3UH53, Q589G5, Q58EX2, Q64487, Q64604, Q64605, Q6V4S5, Q7Z5N4, Q810U3

Diamond homologs: A0A1D5NSM8, A0JNA2, A2AVA0, A2AX52, D3YXF5, O02839, O19063, O35764, O43405, O70340, O76536, O89029, O95502, O96530, P02741, P02743, P06205, P06206, P06207, P06681, P07202, P07629, P08607, P09871, P0C6B8, P10643, P12246, P13944, P14151, P14847, P15697, P18337, P23680, P32018, P47970, P47971, P47972, P48199, P49254, P49262

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COL14A1	up-regulates	ECM_synthesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Collagen biosynthesis and modifying enzymes	8	17.0×	1e-05
Non-integrin membrane-ECM interactions	6	11.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	199
Likely benign	32
Benign	98

Top pathogenic / likely-pathogenic (0)

SpliceAI

6891 predictions. Top by Δscore:

Variant	Effect	Δscore
8:120147802:CTAG:C	acceptor_loss	1.0000
8:120147803:TAG:T	acceptor_loss	1.0000
8:120147804:AGG:A	acceptor_loss	1.0000
8:120158128:A:AG	acceptor_gain	1.0000
8:120158128:AGT:A	acceptor_gain	1.0000
8:120158129:G:GG	acceptor_gain	1.0000
8:120158129:GT:G	acceptor_gain	1.0000
8:120158129:GTG:G	acceptor_gain	1.0000
8:120158242:TTCAG:T	donor_loss	1.0000
8:120158243:TCAG:T	donor_loss	1.0000
8:120158244:CAGG:C	donor_loss	1.0000
8:120158245:AG:A	donor_loss	1.0000
8:120158246:GG:G	donor_loss	1.0000
8:120158247:GTAA:G	donor_loss	1.0000
8:120158248:T:A	donor_loss	1.0000
8:120162421:TATAG:T	acceptor_loss	1.0000
8:120162424:A:AG	acceptor_gain	1.0000
8:120162424:AGG:A	acceptor_loss	1.0000
8:120162425:G:GG	acceptor_gain	1.0000
8:120162567:GAA:G	donor_gain	1.0000
8:120162568:AA:A	donor_gain	1.0000
8:120162570:G:GG	donor_gain	1.0000
8:120168159:A:AG	acceptor_gain	1.0000
8:120168160:G:GG	acceptor_gain	1.0000
8:120196789:A:AG	acceptor_gain	1.0000
8:120196789:AGA:A	acceptor_loss	1.0000
8:120196790:G:A	acceptor_loss	1.0000
8:120196790:G:GG	acceptor_gain	1.0000
8:120196790:GA:G	acceptor_gain	1.0000
8:120196790:GAA:G	acceptor_gain	1.0000

AlphaMissense

11625 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:120158189:T:A	W50R	1.000
8:120158189:T:C	W50R	1.000
8:120196839:T:C	L162P	1.000
8:120196845:A:T	D164V	1.000
8:120196853:T:A	W167R	1.000
8:120196853:T:C	W167R	1.000
8:120196855:G:C	W167C	1.000
8:120196855:G:T	W167C	1.000
8:120197814:T:C	L199P	1.000
8:120197911:A:C	K231N	1.000
8:120197911:A:T	K231N	1.000
8:120199566:G:T	G293W	1.000
8:120203736:T:C	L302P	1.000
8:120196844:G:C	D164H	0.999
8:120196844:G:T	D164Y	0.999
8:120196845:A:C	D164A	0.999
8:120196846:T:A	D164E	0.999
8:120196846:T:G	D164E	0.999
8:120196847:G:C	G165R	0.999
8:120196847:G:T	G165C	0.999
8:120196848:G:A	G165D	0.999
8:120196848:G:T	G165V	0.999
8:120196850:T:C	S166P	0.999
8:120196856:A:C	S168R	0.999
8:120196858:T:A	S168R	0.999
8:120196858:T:G	S168R	0.999
8:120196905:T:C	L184P	0.999
8:120197825:A:C	S203R	0.999
8:120197827:T:A	S203R	0.999
8:120197827:T:G	S203R	0.999

dbSNP variants (sampled 300 via entrez): RS1000000018 (8:120258031 G>A), RS1000002064 (8:120215457 A>T), RS1000010809 (8:120301666 C>T), RS1000071433 (8:120232823 TC>T), RS1000079339 (8:120236753 T>G), RS1000082126 (8:120323718 G>C), RS1000086036 (8:120127955 G>T), RS1000100456 (8:120142181 A>G), RS1000107599 (8:120253583 T>A), RS1000116973 (8:120368995 A>G), RS1000123336 (8:120233057 A>T), RS1000128869 (8:120328438 C>T), RS1000137639 (8:120238627 C>T), RS1000173676 (8:120325469 G>T), RS1000175934 (8:120370986 T>C)

Disease associations

OMIM: gene MIM:120324 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
punctate palmoplantar keratoderma type 1	Supportive	Autosomal dominant
hereditary palmoplantar keratoderma	Limited	Autosomal dominant

Mondo (2): hereditary palmoplantar keratoderma (MONDO:0019272), punctate palmoplantar keratoderma type 1 (MONDO:0019332)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0002671	Basal cell carcinoma
HP:0002860	Squamous cell carcinoma
HP:0002861	Melanoma
HP:0003002	Breast carcinoma
HP:0005584	Renal cell carcinoma
HP:0006725	Pancreatic adenocarcinoma
HP:0008404	Nail dystrophy
HP:0010622	Neoplasm of the skeletal system
HP:0011124	Abnormal epidermal morphology
HP:0012125	Prostate cancer
HP:0012126	Stomach cancer
HP:0012189	Hodgkin lymphoma
HP:0012500	Verrucous papule
HP:0012531	Pain
HP:0025092	Epidermal acanthosis
HP:0025114	Hypergranulosis
HP:0030692	Brain neoplasm
HP:0040162	Orthokeratosis
HP:0040274	Adenocarcinoma of the small intestine
HP:0040276	Adenocarcinoma of the colon
HP:0045059	Hyperkeratotic papule
HP:0100526	Neoplasm of the lung
HP:0100751	Esophageal neoplasm

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002282_19	Parasitemia in Tripanosoma cruzi seropositivity	3.000000e-07
GCST002638_3	Gastritis	2.000000e-06
GCST004071_14	Cerebrospinal T-tau levels	4.000000e-06
GCST008473_31	Visceral fat	1.000000e-06
GCST009028_51	Adverse response to drug	9.000000e-07
GCST90000025_373	Appendicular lean mass	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005528	parasitemia measurement
EFO:0004760	t-tau measurement
EFO:0009658	adverse effect
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066281 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.24	Kd	0.577	nM	CHEMBL5653589
9.24	ED50	0.577	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148111: Binding affinity to human COL14A1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
entinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Triclosan	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
4-nonylphenol	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-tert-octylphenol	affects cotreatment, increases expression	1
rofecoxib	decreases expression	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’,5-brominated diphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Ethanol	increases expression	1
Azacitidine	increases expression	1
Benztropine	affects cotreatment, increases expression	1
Cadmium	increases abundance, increases expression	1
Cannabinoids	increases abundance, decreases expression, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651153	Binding	Binding affinity to human COL14A1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05435638	PHASE1	COMPLETED	Study Designed to Evaluate Safety and Efficacy of 1% Topical Formulation of KM-001 on Type 1 Punctate Palmoplantar Keratoderma or Pachyonychia Congenita Diseases
NCT05956314	PHASE1	COMPLETED	Assessment of KM-001 - Safety, Tolerability, and Efficacy in Patients With PPPK1 or PC