KCP

Summary

KCP (kielin cysteine rich BMP regulator, HGNC:17585) is a protein-coding gene on chromosome 7q32.1, encoding Kielin/chordin-like protein (Q6ZWJ8). Enhances bone morphogenetic protein (BMP) signaling in a paracrine manner.

Predicted to be involved in positive regulation of BMP signaling pathway. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in extracellular space. Predicted to be active in extracellular region.

Source: NCBI Gene 375616 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 290 total
• MANE Select transcript: NM_001366122

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17585
Approved symbol	KCP
Name	kielin cysteine rich BMP regulator
Location	7q32.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33365, NET67
Ensembl gene	ENSG00000135253
Ensembl biotype	protein_coding
OMIM	609344
Entrez	375616

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 retained_intron, 2 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000460528, ENST00000492679, ENST00000610776, ENST00000611280, ENST00000612224, ENST00000613019, ENST00000616669, ENST00000676619, ENST00000676717, ENST00000678812, ENST00000678888, ENST00000679229

RefSeq mRNA: 2 — MANE Select: NM_001366122 NM_001366122, NM_199349

CCDS: CCDS94194

Canonical transcript exons

ENST00000610776 — 40 exons

Exon	Start	End
ENSE00003712612	128878558	128878722
ENSE00003712988	128880997	128881085
ENSE00003713238	128876865	128877311
ENSE00003714896	128890905	128891096
ENSE00003714978	128910601	128910709
ENSE00003715743	128879522	128879623
ENSE00003715852	128903727	128903820
ENSE00003717042	128884781	128884863
ENSE00003717642	128884002	128884122
ENSE00003717808	128892688	128892794
ENSE00003718192	128880386	128880528
ENSE00003718780	128893976	128894055
ENSE00003719614	128891185	128891278
ENSE00003721596	128885097	128885270
ENSE00003725090	128886876	128886966
ENSE00003726174	128879913	128880085
ENSE00003726417	128886655	128886737
ENSE00003727032	128893806	128893899
ENSE00003727782	128888863	128889039
ENSE00003729006	128907101	128907177
ENSE00003729303	128892514	128892607
ENSE00003730372	128890343	128890513
ENSE00003732925	128881937	128882016
ENSE00003734157	128908426	128908568
ENSE00003734462	128879718	128879829
ENSE00003736710	128893391	128893476
ENSE00003738134	128877484	128877790
ENSE00003738627	128886464	128886557
ENSE00003739918	128891451	128891533
ENSE00003743073	128887215	128887300
ENSE00003745323	128893238	128893319
ENSE00003745650	128907264	128907453
ENSE00003746903	128891646	128891819
ENSE00003748220	128892869	128893021
ENSE00003748576	128902777	128902859
ENSE00003748792	128880619	128880721
ENSE00003750305	128894200	128894293
ENSE00003751342	128904056	128904138
ENSE00003752275	128881626	128881725
ENSE00003752537	128906279	128906363

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 94.82.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2377 / max 112.9415, expressed in 342 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86082	0.6635	168
86083	0.4476	167
86077	0.0781	5
86081	0.0350	11
86075	0.0099	4
86076	0.0036	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	94.82	gold quality
cerebellar hemisphere	UBERON:0002245	92.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.91	gold quality
cerebellar cortex	UBERON:0002129	92.81	gold quality
cerebellum	UBERON:0002037	90.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.16	gold quality
metanephros	UBERON:0000081	82.26	gold quality
cortex of kidney	UBERON:0001225	81.98	gold quality
adult mammalian kidney	UBERON:0000082	81.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.90	gold quality
pancreatic ductal cell	CL:0002079	76.52	silver quality
kidney	UBERON:0002113	76.06	gold quality
buccal mucosa cell	CL:0002336	75.50	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.30	gold quality
gastrocnemius	UBERON:0001388	75.23	gold quality
sperm	CL:0000019	75.20	silver quality
small intestine Peyer’s patch	UBERON:0003454	74.39	gold quality
omental fat pad	UBERON:0010414	74.18	gold quality
peritoneum	UBERON:0002358	74.13	gold quality
muscle of leg	UBERON:0001383	74.00	gold quality
esophagus mucosa	UBERON:0002469	73.99	gold quality
prefrontal cortex	UBERON:0000451	73.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.24	gold quality
small intestine	UBERON:0002108	72.66	gold quality
stromal cell of endometrium	CL:0002255	72.64	gold quality
gall bladder	UBERON:0002110	72.47	gold quality
cortical plate	UBERON:0005343	71.93	gold quality
secondary oocyte	CL:0000655	71.72	silver quality
right frontal lobe	UBERON:0002810	69.23	gold quality
mucosa of stomach	UBERON:0001199	68.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	14.89
E-MTAB-9543	yes	5.11
E-ANND-3	yes	4.34
E-MTAB-5061	no	3.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting KCP, 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-6873-3P	100.00	71.42	2626
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-122-5P	97.23	64.92	1024

Literature-anchored findings (GeneRIF, showing 2)

• The KCP was closely associated with heart failure. The regulation of BMP2/7 and TGF-beta1 expression may be the possible mechanisms. (PMID:30144436)
• Kielin/chordin-like protein enhances induction of osteoblast differentiation by Bone Morphogenetic Protein-2. (PMID:37226930)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcp	ENSDARG00000078508
mus_musculus	Kcp	ENSMUSG00000059022
rattus_norvegicus	Kcp	ENSRNOG00000021855

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Kielin/chordin-like protein — Q6ZWJ8 (reviewed: Q6ZWJ8)

Alternative names: Cysteine-rich BMP regulator 2, Cysteine-rich motor neuron 2 protein, Kielin/chordin-like protein 1

All UniProt accessions (4): A0A087WVT8, A0A087WXB2, A0A7I2V446, Q6ZWJ8

UniProt curated annotations — full annotation on UniProt →

Function. Enhances bone morphogenetic protein (BMP) signaling in a paracrine manner. In contrast, it inhibits both the activin-A and TGFB1-mediated signaling pathways.

Subunit / interactions. Interacts with BMP7 and, by doing so, enhances binding to the type I receptors that contains cytoplasmic serine/threonine protein kinase domains. Also able to interact with activin-A and TGFB1.

Subcellular location. Secreted.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZWJ8-3	3	yes
Q6ZWJ8-2	2
Q6ZWJ8-4	4

RefSeq proteins (1): NP_001353051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR001846	VWF_type-D	Domain
IPR014853	VWF/SSPO/ZAN-like_Cys-rich_dom	Domain
IPR036084	Ser_inhib-like_sf	Homologous_superfamily
IPR052424	Kielin_Chordin-BMP_Reg	Family

Pfam: PF00093, PF00094, PF23334

UniProt features (39 total): domain 18, splice variant 6, sequence variant 4, glycosylation site 3, disulfide bond 2, signal peptide 1, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZWJ8-F1	72.35	0.06

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 (2): 1215–1347, 1237–1388

Glycosylation sites (3): 340, 499, 1090

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, HNF1_Q6, LHX3_01, SREBP1_02, GOBP_POSITIVE_REGULATION_OF_BMP_SIGNALING_PATHWAY, NKX62_Q2, RGTTAMWNATT_HNF1_01, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GROSS_HYPOXIA_VIA_ELK3_ONLY_DN, chr7q32, GOBP_RESPONSE_TO_BMP, NKX25_01, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_REGULATION_OF_BMP_SIGNALING_PATHWAY, HNF1_01

GO Biological Process (2): positive regulation of BMP signaling pathway (GO:0030513), hematopoietic progenitor cell differentiation (GO:0002244)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
hemopoiesis	1
cell differentiation	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCP	BMP7	P18075	763
KCP	LRRC8A	Q8IWT6	614
KCP	TTYH2	Q9BSA4	564
KCP	LRRC8E	Q6NSJ5	519
KCP	LRRC8D	Q7L1W4	510
KCP	LRRC8C	Q8TDW0	501
KCP	TTYH3	Q9C0H2	472
KCP	TTYH1	Q9H313	461
KCP	CHRD	Q9H2X0	416
KCP	TGFA	P01135	408
KCP	LRRC8B	Q6P9F7	399
KCP	CNNM1	Q9NRU3	380
KCP	TMEM205	Q6UW68	356
KCP	STARD9	Q9P2P6	349
KCP	MLANA	Q16655	349

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2VEC9, O08644, O08852, O15197, O55225, O88839, O95428, O97507, P00748, P07204, P0C0K6, P0C0K7, P15306, P26010, P26011, P60882, P98140, P98167, Q00657, Q04912, Q04962, Q0V8J4, Q13444, Q2PC93, Q3U492, Q4G0T1, Q5IJ48, Q6GUQ1, Q6MG64, Q6MG84, Q6UVK1, Q6ZRI0, Q6ZWJ8, Q700K0, Q71U07, Q769J6, Q76LX8, Q7Z7M0, Q80YA8, Q8CG65

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	251
Likely benign	22
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

6705 predictions. Top by Δscore:

Variant	Effect	Δscore
7:128865372:CACA:C	acceptor_loss	1.0000
7:128865374:CA:C	acceptor_loss	1.0000
7:128865375:A:AG	acceptor_gain	1.0000
7:128865375:A:AT	acceptor_loss	1.0000
7:128865376:G:GG	acceptor_gain	1.0000
7:128865376:GGCA:G	acceptor_gain	1.0000
7:128865376:GGCAA:G	acceptor_gain	1.0000
7:128879518:GCA:G	donor_loss	1.0000
7:128879520:A:AT	donor_loss	1.0000
7:128879712:GCTCA:G	donor_loss	1.0000
7:128879714:TCA:T	donor_loss	1.0000
7:128879715:CA:C	donor_loss	1.0000
7:128879716:A:AC	donor_gain	1.0000
7:128879716:A:C	donor_loss	1.0000
7:128879717:C:CC	donor_gain	1.0000
7:128879731:T:TA	donor_gain	1.0000
7:128879825:GCACA:G	acceptor_gain	1.0000
7:128879826:CACA:C	acceptor_gain	1.0000
7:128879826:CACAC:C	acceptor_gain	1.0000
7:128879827:ACA:A	acceptor_gain	1.0000
7:128879828:CA:C	acceptor_gain	1.0000
7:128879828:CAC:C	acceptor_gain	1.0000
7:128879830:C:CC	acceptor_gain	1.0000
7:128880385:CGGGG:C	donor_gain	1.0000
7:128880995:A:AC	donor_gain	1.0000
7:128880996:C:CC	donor_gain	1.0000
7:128891735:T:A	donor_gain	1.0000
7:128892510:ATAC:A	donor_loss	1.0000
7:128892512:A:C	donor_loss	1.0000
7:128892513:CCT:C	donor_loss	1.0000

AlphaMissense

10573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:128891491:A:C	F617C	0.996
7:128892978:C:A	W441C	0.996
7:128892978:C:G	W441C	0.996
7:128888997:A:C	F797C	0.995
7:128879967:A:C	F1233C	0.991
7:128892997:A:C	F435C	0.991
7:128878561:C:A	W1376C	0.990
7:128878561:C:G	W1376C	0.990
7:128885227:C:A	W974C	0.990
7:128885227:C:G	W974C	0.990
7:128877687:C:G	C1412S	0.988
7:128877688:A:T	C1412S	0.988
7:128879966:G:C	F1233L	0.987
7:128879966:G:T	F1233L	0.987
7:128879968:A:G	F1233L	0.987
7:128879967:A:G	F1233S	0.986
7:128892728:A:C	F500C	0.986
7:128884821:A:C	F1032C	0.985
7:128891490:G:C	F617L	0.985
7:128891490:G:T	F617L	0.985
7:128891491:A:G	F617S	0.985
7:128891492:A:G	F617L	0.985
7:128877503:C:A	W1473C	0.984
7:128877503:C:G	W1473C	0.984
7:128880473:C:A	W1164C	0.984
7:128880473:C:G	W1164C	0.984
7:128888996:G:C	F797L	0.984
7:128888996:G:T	F797L	0.984
7:128888998:A:G	F797L	0.984
7:128888997:A:G	F797S	0.981

dbSNP variants (sampled 300 via entrez): RS1000137428 (7:128909526 C>T), RS1000341189 (7:128903954 G>A), RS1000403868 (7:128890267 C>A,T), RS1000440640 (7:128897468 TTG>T), RS1000662463 (7:128901767 C>T), RS1000680947 (7:128878287 A>C,G,T), RS1000752859 (7:128878615 C>A,T), RS1000943480 (7:128900713 G>A,C), RS1001007548 (7:128893429 G>A,C), RS1001023687 (7:128879552 A>C,G,T), RS1001065636 (7:128887680 CACAT>C,CACATACAT), RS1001081908 (7:128884801 A>C,G), RS1001203153 (7:128910865 A>G), RS1001306233 (7:128910112 G>A,T), RS1001355323 (7:128893114 G>A,C)

Disease associations

OMIM: gene MIM:609344 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009597_34	Multiple sclerosis	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	increases expression	2
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Glyphosate	affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Epichlorohydrin	affects response to substance	1
Formaldehyde	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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