PKDCC

Summary

PKDCC (protein kinase domain containing, cytoplasmic, HGNC:25123) is a protein-coding gene on chromosome 2p21, encoding Extracellular tyrosine-protein kinase PKDCC (Q504Y2). Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages.

Enables non-membrane spanning protein tyrosine kinase activity. Involved in peptidyl-tyrosine phosphorylation and skeletal system development. Located in extracellular region.

Source: NCBI Gene 91461 — RefSeq curated summary.

At a glance

• Gene–disease (curated): rhizomelic limb shortening with dysmorphic features (Strong, GenCC)
• GWAS associations: 25
• Clinical variants (ClinVar): 205 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_138370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25123
Approved symbol	PKDCC
Name	protein kinase domain containing, cytoplasmic
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	SgK493, Vlk
Ensembl gene	ENSG00000162878
Ensembl biotype	protein_coding
OMIM	614150
Entrez	91461

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000294964, ENST00000401498, ENST00000470578, ENST00000475241, ENST00000475868, ENST00000480099, ENST00000485578, ENST00000490302, ENST00000492861, ENST00000914294, ENST00000953637

RefSeq mRNA: 1 — MANE Select: NM_138370 NM_138370

CCDS: CCDS33186

Canonical transcript exons

ENST00000294964 — 7 exons

Exon	Start	End
ENSE00001825270	42057603	42058517
ENSE00001837883	42048021	42048838
ENSE00003496908	42057221	42057394
ENSE00003501813	42054036	42054307
ENSE00003607943	42054941	42055020
ENSE00003643195	42055286	42055393
ENSE00003669911	42053239	42053361

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5679 / max 441.5971, expressed in 1057 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19910	16.4040	1057
19911	0.1639	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right ovary	UBERON:0002118	99.20	gold quality
left ovary	UBERON:0002119	99.05	gold quality
left uterine tube	UBERON:0001303	98.72	gold quality
gastrocnemius	UBERON:0001388	98.62	gold quality
right coronary artery	UBERON:0001625	98.55	gold quality
left coronary artery	UBERON:0001626	98.55	gold quality
ascending aorta	UBERON:0001496	98.54	gold quality
thoracic aorta	UBERON:0001515	98.52	gold quality
tibial nerve	UBERON:0001323	98.47	gold quality
endocervix	UBERON:0000458	98.43	gold quality
body of uterus	UBERON:0009853	98.43	gold quality
coronary artery	UBERON:0001621	98.40	gold quality
right atrium auricular region	UBERON:0006631	98.35	gold quality
descending thoracic aorta	UBERON:0002345	98.27	gold quality
cardiac atrium	UBERON:0002081	98.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.10	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.98	gold quality
omental fat pad	UBERON:0010414	97.95	gold quality
peritoneum	UBERON:0002358	97.93	gold quality
lower esophagus	UBERON:0013473	97.93	gold quality
aorta	UBERON:0000947	97.91	gold quality
muscle of leg	UBERON:0001383	97.87	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.82	gold quality
mucosa of stomach	UBERON:0001199	97.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.74	gold quality
apex of heart	UBERON:0002098	97.60	gold quality
popliteal artery	UBERON:0002250	97.52	gold quality
tibial artery	UBERON:0007610	97.52	gold quality
transverse colon	UBERON:0001157	97.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	420.74
E-ANND-3	yes	9.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting PKDCC, 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-3120-5P	100.00	65.56	965
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337

Literature-anchored findings (GeneRIF, showing 11)

• our results suggest that genes CA10 and also SGK493 may be an important risk factor for asthma development, especially for a nonatopic phenotype. (PMID:24407380)
• VLK is rapidly and quantitatively secreted from platelets in response to stimuli and can tyrosine phosphorylate coreleased proteins utilizing endogenous as well as exogenous ATP sources. (PMID:25171405)
• The Fam20C-and VLK-family of kinases mediate the phosphorylation of proteins in the secretory pathway and extracellular space.Mutation in several secretory pathway kinases cause human disease (PMID:25862977)
• VLK secretion can be regulated by external cues, intracellular signal proteins, and mechanical stretch, and VLK can in turn regulate TyrP of ECM proteins secreted by trabecular meshwork cells and control cell shape, actin stress fibers, and focal adhesions. (PMID:27591737)
• Each patient had a homozygous gene disrupting variant in PKDCC considered to explain the skeletal phenotypes shared by both. (PMID:30478137)
• Taken together, these results suggest that Vlk may function as a signaling regulator in extracellular space to modulate the Hedgehog pathway (PMID:31845979)
• The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation. (PMID:34329392)
• The prevalence and phenotypic range associated with biallelic PKDCC variants. (PMID:36896672)
• Prenatal diagnosis to identify compound heterozygous variants in PKDCC that causes rhizomelic limb shortening with dysmorphic features in a fetus from China. (PMID:37592254)
• A common cis-regulatory variant impacts normal-range and disease-associated human facial shape through regulation of PKDCC during chondrogenesis. (PMID:38483448)
• Identification of bone mineral density associated genes with shared genetic architectures across multiple tissues: Functional insights for EPDR1, PKDCC, and SPTBN1. (PMID:38683846)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkdcca	ENSDARG00000035161
mus_musculus	Pkdcc	ENSMUSG00000024247
rattus_norvegicus	Pkdcc	ENSRNOG00000004205

Paralogs (2): MAP3K7 (ENSG00000135341), MAP3K7CL (ENSG00000156265)

Protein

Protein identifiers

Extracellular tyrosine-protein kinase PKDCC — Q504Y2 (reviewed: Q504Y2)

Alternative names: Protein kinase domain-containing protein, cytoplasmic, Protein kinase-like protein SgK493, Sugen kinase 493, Vertebrate lonesome kinase

All UniProt accessions (2): Q504Y2, F8WB71

UniProt curated annotations — full annotation on UniProt →

Function. Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages. Mediates phosphorylation of MMP1, MMP13, MMP14, MMP19 and ERP29. Probably plays a role in platelets: rapidly and quantitatively secreted from platelets in response to stimulation of platelet degranulation. May also have serine/threonine protein kinase activity. Required for longitudinal bone growth through regulation of chondrocyte differentiation. May be indirectly involved in protein transport from the Golgi apparatus to the plasma membrane.

Subcellular location. Secreted. Golgi apparatus.

Tissue specificity. Highly expressed in platelets.

Post-translational modifications. N-glycosylated. Phosphorylated on tyrosines; probably via autophosphorylation.

Disease relevance. Rhizomelic limb shortening with dysmorphic features (RLSDF) [MIM:618821] An autosomal recessive skeletal dysplasia characterized by rhizomelic shortening of limbs as well as variable dysmorphic features, including macrocephaly, short neck, micrognathia, mild proptosis, downslanting palpebral fissures, depressed or broad nasal bridge and long philtrum. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily.

RefSeq proteins (1): NP_612379* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR022049	FAM69_kinase_dom	Domain
IPR042983	PKDCC	Family

Pfam: PF12260

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (20 total): glycosylation site 6, compositionally biased region 4, binding site 2, modified residue 2, signal peptide 1, chain 1, sequence variant 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q504Y2-F1	82.96	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 278 (proton acceptor)

Ligand- & substrate-binding residues (2): 166; 144–152

Post-translational modifications (2): 148, 177

Glycosylation sites (6): 137, 320, 369, 400, 460, 484

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 280 (showing top): GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_EMBRYONIC_DIGESTIVE_TRACT_DEVELOPMENT, GOBP_BONE_MINERALIZATION

GO Biological Process (15): skeletal system development (GO:0001501), protein transport (GO:0015031), peptidyl-tyrosine phosphorylation (GO:0018108), cell differentiation (GO:0030154), bone mineralization (GO:0030282), positive regulation of bone mineralization (GO:0030501), positive regulation of chondrocyte differentiation (GO:0032332), limb morphogenesis (GO:0035108), multicellular organism growth (GO:0035264), negative regulation of Golgi to plasma membrane protein transport (GO:0042997), lung alveolus development (GO:0048286), embryonic digestive tract development (GO:0048566), roof of mouth development (GO:0060021), ossification (GO:0001503), protein phosphorylation (GO:0006468)

GO Molecular Function (7): protein kinase activity (GO:0004672), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein tyrosine kinase activity (GO:0004713), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): extracellular region (GO:0005576), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	2
anatomical structure development	2
system development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
cellular developmental process	1
ossification	1
biomineral tissue development	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
positive regulation of cell differentiation	1
positive regulation of cartilage development	1
appendage morphogenesis	1
limb development	1
developmental growth	1
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
negative regulation of protein transport	1
negative regulation of protein localization to plasma membrane	1
lung development	1
digestive tract development	1
embryonic organ development	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
protein kinase activity	1

Protein interactions and networks

STRING

1646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKDCC	FAM20C	Q8IXL6	677
PKDCC	PRR35	P0CG20	565
PKDCC	KCNG3	Q8TAE7	561
PKDCC	DIPK1A	Q5T7M9	519
PKDCC	POMK	Q9H5K3	519
PKDCC	KBTBD12	Q3ZCT8	507
PKDCC	RRP36	Q96EU6	481
PKDCC	DIPK2B	Q9H7Y0	479
PKDCC	TOGARAM1	Q9Y4F4	455
PKDCC	FAM20B	O75063	453
PKDCC	FAM20A	Q96MK3	450
PKDCC	IHO1	Q8IYA8	445
PKDCC	CDH8	P55286	438
PKDCC	SIPA1L2	Q9P2F8	437
PKDCC	VWC2	Q2TAL6	436

IntAct

5 interactions, top by confidence:

A	B	Type	Score
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PKDCC	PDCD5	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): PKDCC (Affinity Capture-MS), PKDCC (Affinity Capture-MS), PKDCC (Affinity Capture-RNA), PKDCC (Affinity Capture-RNA), PKDCC (Affinity Capture-MS), PDCD5 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CANX (Affinity Capture-MS), STIP1 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT5 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), AK2 (Affinity Capture-MS)

ESM2 similar proteins: A2A9Q0, A5PKD8, A9JSM3, D4A2Q0, E7ERA6, F1SAM7, F2Z333, P0CG25, Q07303, Q0IIA6, Q1RMK9, Q24JP5, Q2MJR0, Q2WF71, Q3MIP1, Q3UV16, Q3ZCQ3, Q504Y2, Q5EBM0, Q5GH56, Q5GH64, Q5GH72, Q5RJI4, Q5SZI1, Q641Q3, Q6IEE6, Q6IQX7, Q6P6N5, Q6UKI2, Q6ZMC9, Q6ZVW7, Q86UD0, Q8IUW3, Q8IZ52, Q8K064, Q8N4K4, Q8NAC3, Q8NBR0, Q8NCL9, Q8NFR9

Diamond homologs: Q504Y2, Q5RJI4, Q91820

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	113
Likely benign	60
Benign	9

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1457022	NC_000002.11:g.(?42275340)(42275998_?)del	Pathogenic
1727206	NM_138370.3(PKDCC):c.939dup (p.Leu314fs)	Pathogenic
2753588	NM_138370.3(PKDCC):c.226_235del (p.Gly76fs)	Pathogenic
2861261	NM_138370.3(PKDCC):c.499del (p.Ala167fs)	Pathogenic
3627565	NM_138370.3(PKDCC):c.1132dup (p.Val378fs)	Pathogenic
3695668	NM_138370.3(PKDCC):c.707del (p.Gly236fs)	Pathogenic
3775649	NM_138370.3(PKDCC):c.754C>T (p.Arg252Ter)	Pathogenic
521769	NM_138370.3(PKDCC):c.651C>A (p.Tyr217Ter)	Pathogenic
1334386	NM_138370.3(PKDCC):c.1127G>A (p.Trp376Ter)	Likely pathogenic
1480267	NM_138370.3(PKDCC):c.1115-2A>G	Likely pathogenic
1722583	NM_138370.3(PKDCC):c.290_320del (p.Leu97fs)	Likely pathogenic
1803946	NM_138370.3(PKDCC):c.228dup (p.Pro77fs)	Likely pathogenic
3897945	NM_138370.3(PKDCC):c.640-2A>T	Likely pathogenic

SpliceAI

912 predictions. Top by Δscore:

Variant	Effect	Δscore
2:42053234:CCCA:C	acceptor_loss	1.0000
2:42053235:CCAG:C	acceptor_loss	1.0000
2:42053236:CA:C	acceptor_loss	1.0000
2:42053237:A:AG	acceptor_gain	1.0000
2:42053237:A:AT	acceptor_loss	1.0000
2:42053238:G:C	acceptor_loss	1.0000
2:42053238:G:GA	acceptor_gain	1.0000
2:42053238:GCTC:G	acceptor_gain	1.0000
2:42053238:GCTCT:G	acceptor_gain	1.0000
2:42053346:G:GT	donor_gain	1.0000
2:42053359:CGAGT:C	donor_loss	1.0000
2:42053360:GA:G	donor_gain	1.0000
2:42053361:AGT:A	donor_loss	1.0000
2:42053362:G:GG	donor_gain	1.0000
2:42053362:GTG:G	donor_loss	1.0000
2:42053367:C:G	donor_gain	1.0000
2:42053374:G:GT	donor_gain	1.0000
2:42054230:G:GT	donor_gain	1.0000
2:42054231:A:T	donor_gain	1.0000
2:42054370:G:GT	donor_gain	1.0000
2:42054935:CCACA:C	acceptor_loss	1.0000
2:42054938:CAGGT:C	acceptor_loss	1.0000
2:42054940:G:GA	acceptor_loss	1.0000
2:42055280:CTGCA:C	acceptor_loss	1.0000
2:42055281:TGCA:T	acceptor_loss	1.0000
2:42055282:GCAGG:G	acceptor_loss	1.0000
2:42055283:CAGGA:C	acceptor_loss	1.0000
2:42055284:A:AG	acceptor_gain	1.0000
2:42055284:A:T	acceptor_loss	1.0000
2:42055285:G:GG	acceptor_gain	1.0000

AlphaMissense

3132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:42054124:T:C	F284S	1.000
2:42048649:G:C	K150N	0.999
2:42048649:G:T	K150N	0.999
2:42048697:G:C	K166N	0.999
2:42048697:G:T	K166N	0.999
2:42048784:G:C	K195N	0.999
2:42048784:G:T	K195N	0.999
2:42048793:G:C	K198N	0.999
2:42048793:G:T	K198N	0.999
2:42048795:A:T	E199V	0.999
2:42053344:T:A	W249R	0.999
2:42053344:T:C	W249R	0.999
2:42053346:G:C	W249C	0.999
2:42053346:G:T	W249C	0.999
2:42054105:G:C	D278H	0.999
2:42054106:A:T	D278V	0.999
2:42054109:T:C	F279S	0.999
2:42054123:T:C	F284L	0.999
2:42054124:T:G	F284C	0.999
2:42054125:T:A	F284L	0.999
2:42054125:T:G	F284L	0.999
2:42054156:G:C	D295H	0.999
2:42054157:A:C	D295A	0.999
2:42054157:A:T	D295V	0.999
2:42054158:C:A	D295E	0.999
2:42054158:C:G	D295E	0.999
2:42054163:A:T	D297V	0.999
2:42054166:A:T	D298V	0.999
2:42054290:C:A	N339K	0.999
2:42054290:C:G	N339K	0.999

dbSNP variants (sampled 300 via entrez): RS1000304247 (2:42053734 C>T), RS1000563945 (2:42048507 C>G,T), RS1000803569 (2:42047569 C>G), RS1001004575 (2:42052318 C>T), RS1001020931 (2:42056369 T>A), RS1001046189 (2:42052463 T>C), RS1001161009 (2:42057776 T>C), RS1002144743 (2:42056686 C>T), RS1002379923 (2:42051249 C>G,T), RS1002473841 (2:42058162 C>A,T), RS1002755675 (2:42051483 T>G), RS1002946258 (2:42046470 G>A), RS1003219567 (2:42047751 G>A,C), RS1003656667 (2:42055969 G>A), RS1003746021 (2:42047482 C>T)

Disease associations

OMIM: gene MIM:614150 | disease phenotypes: MIM:618821

GenCC curated gene-disease

Disease	Classification	Inheritance
rhizomelic limb shortening with dysmorphic features	Strong	Autosomal recessive

Mondo (2): rhizomelic limb shortening with dysmorphic features (MONDO:0032935), skeletal dysplasia (MONDO:0018230)

Orphanet (1): Primary bone dysplasia (Orphanet:364526)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000256	Macrocephaly
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000954	Single transverse palmar crease
HP:0000956	Acanthosis nigricans
HP:0001187	Hyperextensibility of the finger joints
HP:0001212	Prominent fingertip pads
HP:0001348	Brisk reflexes
HP:0001357	Plagiocephaly
HP:0001513	Obesity
HP:0001601	Laryngomalacia
HP:0001655	Patent foramen ovale
HP:0002188	Delayed CNS myelination
HP:0002829	Arthralgia
HP:0002999	Patellar dislocation
HP:0006467	Limited shoulder movement
HP:0008905	Rhizomelia
HP:0009237	Short 5th finger
HP:0009778	Short thumb
HP:0011220	Prominent forehead
HP:0012623	Stage 1 chronic kidney disease
HP:0040024	Clinodactyly of the 3rd finger

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000540_1	Atopy	2.000000e-06
GCST002563_2	Hypospadias	2.000000e-10
GCST003989_28	Chin dimples	4.000000e-13
GCST004088_1	Nonsyndromic cleft lip with or without cleft palate	2.000000e-10
GCST004088_2	Nonsyndromic cleft lip with or without cleft palate	6.000000e-13
GCST005795_14	Femoral neck bone mineral density	6.000000e-09
GCST006481_14	Lung function (FEV1)	3.000000e-08
GCST006481_36	Lung function (FEV1)	8.000000e-08
GCST006585_1309	Blood protein levels	6.000000e-18
GCST006979_923	Heel bone mineral density	2.000000e-20
GCST007429_65	Lung function (FVC)	7.000000e-12
GCST007432_2	FEV1	8.000000e-10
GCST007691_22	Femoral neck bone mineral density	1.000000e-09
GCST007989_4	Facial morphology traits (63 three-dimensional facial segments)	3.000000e-14
GCST010697_30	Cortical surface area (min-P)	3.000000e-08
GCST010698_38	Subcortical volume (min-P)	7.000000e-27
GCST010699_83	Brain morphology (min-P)	1.000000e-14
GCST010700_62	Cortical thickness (MOSTest)	2.000000e-09
GCST010701_49	Cortical surface area (MOSTest)	3.000000e-18
GCST010702_1	Subcortical volume (MOSTest)	2.000000e-08
GCST010703_233	Brain morphology (MOSTest)	2.000000e-12
GCST012490_473	Femur bone mineral density x serum urate levels interaction	9.000000e-10
GCST012490_73	Femur bone mineral density x serum urate levels interaction	1.000000e-10
GCST90002383_165	Hematocrit	7.000000e-10
GCST90002384_44	Hemoglobin	2.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip
EFO:0007785	femoral neck bone mineral density
EFO:0004314	forced expiratory volume
EFO:0009270	heel bone mineral density
EFO:0004312	vital capacity
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004531	urate measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — SgK493 family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Cadmium	increases expression, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, decreases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Acetaldehyde	decreases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Copper	affects binding, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AX	Abcam HeLa PKDCC KO	Cancer cell line	Female
CVCL_TD98	HAP1 PKDCC (-) 1	Cancer cell line	Male
CVCL_TD99	HAP1 PKDCC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001754	Not specified	COMPLETED	Study of Skeletal Disorders and Short Stature
NCT02762318	Not specified	TERMINATED	Identification and Characterization of Bone-related Genetic Variants in Families
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT05247645	Not specified	RECRUITING	Data Collection of Patients With Rare Bone Diseases
NCT05876416	Not specified	RECRUITING	Decoding the Genetic Landscape of Skeletal Diseases
NCT05991609	Not specified	ACTIVE_NOT_RECRUITING	Extreme Morphology and Metabolic Health
NCT06002373	Not specified	UNKNOWN	Assessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients