CHRD

Summary

CHRD (chordin, HGNC:1949) is a protein-coding gene on chromosome 3q27.1, encoding Chordin (Q9H2X0). Dorsalizing factor.

This gene encodes a secreted protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta-like bone morphogenetic proteins and sequestering them in latent complexes. The encoded protein may also have roles in organogenesis and during adulthood. It has been suggested that this gene could be a candidate gene for Cornelia de Lange syndrome. Reduced expression of this gene results in enhanced bone regeneration. Alternative splicing results in multiple transcript variants. Other alternative splice variants have been described but their full length sequence has not been determined.

Source: NCBI Gene 8646 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 196 total
• MANE Select transcript: NM_003741

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1949
Approved symbol	CHRD
Name	chordin
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000090539
Ensembl biotype	protein_coding
OMIM	603475
Entrez	8646

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 10 retained_intron, 9 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000204604, ENST00000348986, ENST00000356534, ENST00000420973, ENST00000448472, ENST00000450923, ENST00000459711, ENST00000460627, ENST00000461120, ENST00000461684, ENST00000464833, ENST00000470150, ENST00000482014, ENST00000482805, ENST00000485883, ENST00000486066, ENST00000496527, ENST00000876248, ENST00000876249, ENST00000876250, ENST00000962070, ENST00000962071, ENST00000962072

RefSeq mRNA: 4 — MANE Select: NM_003741 NM_001304472, NM_001304473, NM_001304474, NM_003741

CCDS: CCDS3266, CCDS77868

Canonical transcript exons

ENST00000204604 — 23 exons

Exon	Start	End
ENSE00000871259	184382856	184382938
ENSE00003461719	184386845	184386938
ENSE00003485221	184381235	184381364
ENSE00003498389	184389367	184389829
ENSE00003507055	184383312	184383418
ENSE00003511936	184386492	184386755
ENSE00003526488	184381496	184381624
ENSE00003529058	184388893	184388995
ENSE00003560460	184383016	184383163
ENSE00003570841	184382389	184382530
ENSE00003572841	184386046	184386159
ENSE00003579323	184383523	184383642
ENSE00003580337	184385018	184385238
ENSE00003592047	184381933	184382020
ENSE00003618009	184387374	184387477
ENSE00003643943	184384537	184384693
ENSE00003643981	184380692	184380795
ENSE00003657362	184387051	184387107
ENSE00003666150	184381716	184381815
ENSE00003666567	184382634	184382774
ENSE00003672403	184388587	184388741
ENSE00003689410	184387931	184388033
ENSE00003978337	184380054	184380466

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 98.15.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9088 / max 103.3772, expressed in 537 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40211	1.0892	405
40209	0.4065	136
40212	0.2664	111
40210	0.1466	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.07	gold quality
cerebellar hemisphere	UBERON:0002245	97.85	gold quality
cerebellar cortex	UBERON:0002129	97.83	gold quality
cerebellum	UBERON:0002037	96.83	gold quality
cerebellar vermis	UBERON:0004720	96.68	gold quality
paraflocculus	UBERON:0005351	95.20	gold quality
endocervix	UBERON:0000458	94.64	gold quality
body of uterus	UBERON:0009853	94.19	gold quality
right frontal lobe	UBERON:0002810	92.38	gold quality
decidua	UBERON:0002450	91.19	gold quality
metanephros cortex	UBERON:0010533	90.92	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.54	gold quality
right ovary	UBERON:0002118	90.32	gold quality
apex of heart	UBERON:0002098	89.96	gold quality
liver	UBERON:0002107	89.66	gold quality
left ovary	UBERON:0002119	89.02	gold quality
ectocervix	UBERON:0012249	88.61	gold quality
body of pancreas	UBERON:0001150	88.29	gold quality
left uterine tube	UBERON:0001303	88.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.94	gold quality
anterior cingulate cortex	UBERON:0009835	87.75	gold quality
cingulate cortex	UBERON:0003027	87.73	gold quality
mucosa of stomach	UBERON:0001199	87.64	gold quality
frontal pole	UBERON:0002795	87.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.14	gold quality
left adrenal gland	UBERON:0001234	86.81	gold quality
frontal cortex	UBERON:0001870	86.78	gold quality
left adrenal gland cortex	UBERON:0035825	86.78	gold quality
right adrenal gland	UBERON:0001233	86.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	7.08
E-ANND-3	yes	6.03
E-MTAB-6142	no	1.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, GSC, LHX1, NEUROG1, PRDM1, SMAD7

miRNA regulators (miRDB)

44 targeting CHRD, 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-188-3P	100.00	68.76	1240
HSA-MIR-4500	99.99	72.72	2367
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-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4447	99.85	67.81	2900
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-8077	99.17	66.67	862

Literature-anchored findings (GeneRIF, showing 8)

• Alternatively spliced variants have different patterns of expression to influence BMP activity in varying physiolgical situations. (PMID:11472837)
• results suggest that CHRD could participate in regulating BMP activity in normal ovarian surface epithelium physiology, and that its mis-expression in ovarian surface epithelium may facilitate cancer incidence and/or progression (PMID:16449796)
• Bone morphogenetic protein (BMP) chordin is produced endogenously during osteogenic differentiation of human mesenchymal stem cells (MSCs); blockade of bone morphogenetic inhibitor chordin increases the rate of osteogenic differentiation of MSCs in vitro. (PMID:18533030)
• Noggin and chordin were also expressed most intensely in areas of cartilage formation and there was no difference in their expression between the non-hypertrophic and hypertrophic chondrocytes. (PMID:19023570)
• there was no difference in the expression of the noggin and chordin between healing and nonhealing fractures (PMID:19058174)
• chordin silencing increased osteogenic differentiation without supplemented BMP-2. (PMID:23931154)
• C-terminal chordin domains play an important role in Bone morphogenetic protein regulation. (PMID:25157165)
• Data suggest CHRD (chordin) cleavage by tolloid-like metalloproteinases is insufficient to regulate BMP(bone morphogenetic protein)/BMPR signaling; CHRD fragments and TSG (twisted gastrulation protein) contribute to inhibition of BMP/BMPR signaling. (PMID:26517884)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Chrd	ENSMUSG00000006958
rattus_norvegicus	Chrd	ENSRNOG00000001750

Paralogs (19): CHRDL2 (ENSG00000054938), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), 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

Chordin — Q9H2X0 (reviewed: Q9H2X0)

All UniProt accessions (2): Q9H2X0, E7ESX1

UniProt curated annotations — full annotation on UniProt →

Function. Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes.

Subunit / interactions. Interacts with TWSG1 and/or BMP4.

Subcellular location. Secreted.

Tissue specificity. Expressed at the highest level in liver.

Post-translational modifications. Cleaved by tolloid proteases; cleavage participates in dorsoventral patterning during early development.

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

Similarity. Belongs to the chordin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9H2X0-1	1	yes
Q9H2X0-2	2
Q9H2X0-3	3
Q9H2X0-4	4
Q9H2X0-5	5

RefSeq proteins (4): NP_001291401, NP_001291402, NP_001291403, NP_003732* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR010895	CHRD	Domain
IPR016353	Chordin	Family
IPR052278	Chordin-like_regulators	Family

Pfam: PF00093, PF07452

UniProt features (35 total): domain 8, splice variant 7, sequence conflict 6, glycosylation site 4, region of interest 3, compositionally biased region 3, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2X0-F1	73.95	0.26

Functional residue map

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

Glycosylation sites (4): 217, 351, 365, 434

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, ACTACCT_MIR196A_MIR196B, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEURAL_TUBE_DEVELOPMENT, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION

GO Biological Process (13): skeletal system development (GO:0001501), positive regulation of mesenchymal cell proliferation (GO:0002053), dorsal/ventral pattern formation (GO:0009953), spinal cord dorsal/ventral patterning (GO:0021513), negative regulation of cell migration (GO:0030336), BMP signaling pathway (GO:0030509), negative regulation of BMP signaling pathway (GO:0030514), floor plate development (GO:0033504), negative regulation of osteoblast differentiation (GO:0045668), positive regulation of cell adhesion (GO:0045785), multicellular organism development (GO:0007275), pattern specification process (GO:0007389), system development (GO:0048731)

GO Molecular Function (3): cytokine binding (GO:0019955), BMP binding (GO:0036122), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
multicellular organismal process	2
multicellular organism development	2
system development	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
regionalization	1
dorsal/ventral pattern formation	1
spinal cord patterning	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
neural tube development	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
protein binding	1
cytokine binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1520 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRD	BMP4	P12644	992
CHRD	BMP2	P12643	986
CHRD	TWSG1	Q9GZX9	945
CHRD	BMP1	P13497	933
CHRD	NOG	Q13253	909
CHRD	BMP7	P18075	900
CHRD	TLL1	O43897	895
CHRD	TLL2	Q9Y6L7	875
CHRD	FST	P19883	846
CHRD	TSKU	Q8WUA8	834
CHRD	VWC2	Q2TAL6	819
CHRD	BMP5	P22003	776
CHRD	BMPER	Q8N8U9	773
CHRD	VWF	P04275	754
CHRD	BGN	P13247	747

IntAct

209 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	CHRD	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	CHRD	psi-mi:“MI:0915”(physical association)	0.720
CHRD	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
CHRD	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	CHRD	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	CHRD	psi-mi:“MI:0915”(physical association)	0.720
CHRD	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
CHRD	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
HOXA1	CHRD	psi-mi:“MI:0915”(physical association)	0.670
CHRD	HOXA1	psi-mi:“MI:0915”(physical association)	0.670
BMP1	CHRD	psi-mi:“MI:0194”(cleavage reaction)	0.620
MEOX2	CHRD	psi-mi:“MI:0915”(physical association)	0.560
CHRD		psi-mi:“MI:0915”(physical association)	0.560
CHRD	PLSCR1	psi-mi:“MI:0915”(physical association)	0.560
SPRY2	CHRD	psi-mi:“MI:0915”(physical association)	0.560
CHRD	OTX1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	CHRD	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	CHRD	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	CHRD	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (98): CHRD (Two-hybrid), CHRD (Two-hybrid), CHRD (Two-hybrid), CHRD (Two-hybrid), CHRD (Two-hybrid), SPRY2 (Two-hybrid), KRTAP9-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), CATSPER1 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: O57472, P07996, P35441, P35448, Q28178, Q5FW85, Q63148, Q6WN34, Q76LD0, Q8AWW5, Q8CJ69, Q8VEA6, Q91713, Q9H2X0, Q9JLL0, Q9Z0E2, B2RUY7, P02452, P02453, P02454, P02457, P02458, P02459, P05997, P11087, Q3U492, Q3U962, Q6P4Z2, Q7T3Q2, Q90ZD5, Q91717, Q920C1, Q9BU40

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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
Keratinization	20	17.1×	2e-17

GO biological processes:

GO term	Partners	Fold	FDR
animal organ development	5	51.6×	3e-05
negative regulation of ERK1 and ERK2 cascade	5	15.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2716 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184380463:GCAG:G	donor_gain	1.0000
3:184380464:CAG:C	donor_loss	1.0000
3:184380465:AGGTA:A	donor_loss	1.0000
3:184380468:T:A	donor_loss	1.0000
3:184380792:GGCG:G	donor_gain	1.0000
3:184380793:GCG:G	donor_gain	1.0000
3:184380793:GCGG:G	donor_gain	1.0000
3:184381226:C:CA	acceptor_gain	1.0000
3:184381227:G:A	acceptor_gain	1.0000
3:184381233:A:AG	acceptor_gain	1.0000
3:184381234:G:GG	acceptor_gain	1.0000
3:184381363:GGGT:G	donor_loss	1.0000
3:184381364:GGT:G	donor_loss	1.0000
3:184381487:C:CA	acceptor_gain	1.0000
3:184381492:GCA:G	acceptor_loss	1.0000
3:184381493:CA:C	acceptor_loss	1.0000
3:184381493:CAG:C	acceptor_gain	1.0000
3:184381494:A:AG	acceptor_gain	1.0000
3:184381494:A:T	acceptor_loss	1.0000
3:184381494:AGA:A	acceptor_gain	1.0000
3:184381495:G:GC	acceptor_gain	1.0000
3:184381495:GA:G	acceptor_gain	1.0000
3:184381495:GAG:G	acceptor_gain	1.0000
3:184381495:GAGC:G	acceptor_gain	1.0000
3:184381597:G:GT	donor_gain	1.0000
3:184381598:A:T	donor_gain	1.0000
3:184381623:GG:G	donor_gain	1.0000
3:184381623:GGGT:G	donor_loss	1.0000
3:184381624:GG:G	donor_gain	1.0000
3:184381625:G:GG	donor_gain	1.0000

AlphaMissense

6060 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184380735:G:C	W64C	1.000
3:184380735:G:T	W64C	1.000
3:184387423:G:C	W799C	1.000
3:184387423:G:T	W799C	1.000
3:184381277:T:A	C99S	0.999
3:184381278:G:C	C99S	0.999
3:184386713:G:C	W718C	0.999
3:184386713:G:T	W718C	0.999
3:184387421:T:A	W799R	0.999
3:184387421:T:C	W799R	0.999
3:184387442:T:C	F806L	0.999
3:184387443:T:G	F806C	0.999
3:184387444:T:A	F806L	0.999
3:184387444:T:G	F806L	0.999
3:184387457:T:A	C811S	0.999
3:184387457:T:C	C811R	0.999
3:184387458:G:C	C811S	0.999
3:184387466:T:A	C814S	0.999
3:184387466:T:C	C814R	0.999
3:184387467:G:A	C814Y	0.999
3:184387467:G:C	C814S	0.999
3:184387952:T:A	C825S	0.999
3:184387953:G:A	C825Y	0.999
3:184387953:G:C	C825S	0.999
3:184388687:G:C	W885C	0.999
3:184388687:G:T	W885C	0.999
3:184380733:T:A	W64R	0.998
3:184380733:T:C	W64R	0.998
3:184380781:T:A	C80S	0.998
3:184380782:G:C	C80S	0.998

dbSNP variants (sampled 300 via entrez): RS1000875801 (3:184381657 G>C), RS1001837170 (3:184388070 G>A), RS1002536924 (3:184378174 A>G), RS1002879158 (3:184379020 C>T), RS1003060313 (3:184385631 A>C,G,T), RS1003133169 (3:184390090 C>T), RS1003282237 (3:184390766 G>A), RS1003435882 (3:184385391 G>A), RS1003508317 (3:184389910 G>A,C), RS1003801897 (3:184383728 C>A,T), RS1003956894 (3:184390038 A>G), RS1003987981 (3:184390466 G>A), RS1004406826 (3:184388180 A>T), RS1004821616 (3:184380880 G>A,C), RS1005012756 (3:184381441 G>A,C)

Disease associations

OMIM: gene MIM:603475 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Limited	AR

Mondo (1): congenital heart disease (MONDO:0005453)

Orphanet (1): Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000580_3	Platelet count	5.000000e-11
GCST002875_76	Diisocyanate-induced asthma	3.000000e-06
GCST004607_267	Plateletcrit	1.000000e-09
GCST010396_295	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-08
GCST90002400_418	Plateletcrit	4.000000e-46
GCST90002402_669	Platelet count	4.000000e-42

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0006995	response to diisocyanate
EFO:0007985	platelet crit
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Estradiol	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Indomethacin	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Silicon Dioxide	decreases expression	1
Tamoxifen	affects expression	1
Triclosan	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Raloxifene Hydrochloride	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE