FGFRL1

Summary

FGFRL1 (fibroblast growth factor receptor like 1, HGNC:3693) is a protein-coding gene on chromosome 4p16.3, encoding Fibroblast growth factor receptor-like 1 (Q8N441). Has a negative effect on cell proliferation.

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. A marked difference between this gene product and the other family members is its lack of a cytoplasmic tyrosine kinase domain. The result is a transmembrane receptor that could interact with other family members and potentially inhibit signaling. Multiple alternatively spliced transcript variants encoding the same isoform have been found for this gene.

Source: NCBI Gene 53834 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 381 total
• Phenotypes (HPO): 93
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001004356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3693
Approved symbol	FGFRL1
Name	fibroblast growth factor receptor like 1
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	FGFR5
Ensembl gene	ENSG00000127418
Ensembl biotype	protein_coding
OMIM	605830
Entrez	53834

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000264748, ENST00000398484, ENST00000504138, ENST00000507339, ENST00000510644, ENST00000512174, ENST00000512562, ENST00000890917, ENST00000890918, ENST00000890919, ENST00000890920, ENST00000940441, ENST00000940442, ENST00000943807, ENST00000943808

RefSeq mRNA: 4 — MANE Select: NM_001004356 NM_001004356, NM_001004358, NM_001370296, NM_021923

CCDS: CCDS3344

Canonical transcript exons

ENST00000510644 — 7 exons

Exon	Start	End
ENSE00000872478	1022203	1022475
ENSE00000872479	1023641	1023721
ENSE00000872480	1023817	1024101
ENSE00001310651	1024311	1024664
ENSE00001533357	1012470	1012564
ENSE00002043972	1024905	1026898
ENSE00002059756	1011626	1011954

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.9490 / max 288.7701, expressed in 1750 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46538	13.2084	1728
46539	0.8687	415
46537	0.8501	595
46534	0.4442	259
46535	0.2929	171
46540	0.1922	61
46536	0.0925	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.95	gold quality
left lobe of thyroid gland	UBERON:0001120	96.17	gold quality
right lobe of thyroid gland	UBERON:0001119	95.38	gold quality
body of pancreas	UBERON:0001150	95.04	gold quality
thyroid gland	UBERON:0002046	94.93	gold quality
descending thoracic aorta	UBERON:0002345	94.72	gold quality
ascending aorta	UBERON:0001496	93.98	gold quality
thoracic aorta	UBERON:0001515	93.98	gold quality
left adrenal gland	UBERON:0001234	93.80	gold quality
left adrenal gland cortex	UBERON:0035825	93.80	gold quality
right adrenal gland	UBERON:0001233	93.63	gold quality
right adrenal gland cortex	UBERON:0035827	93.58	gold quality
adrenal gland	UBERON:0002369	92.60	gold quality
adrenal cortex	UBERON:0001235	92.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.25	gold quality
right lobe of liver	UBERON:0001114	92.08	gold quality
stromal cell of endometrium	CL:0002255	91.67	gold quality
adrenal tissue	UBERON:0018303	91.59	gold quality
aorta	UBERON:0000947	91.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.75	gold quality
left uterine tube	UBERON:0001303	90.58	gold quality
cerebellar hemisphere	UBERON:0002245	90.39	gold quality
cerebellar cortex	UBERON:0002129	90.19	gold quality
body of stomach	UBERON:0001161	89.69	gold quality
omental fat pad	UBERON:0010414	89.48	gold quality
popliteal artery	UBERON:0002250	89.44	gold quality
peritoneum	UBERON:0002358	89.44	gold quality
minor salivary gland	UBERON:0001830	89.41	gold quality
tibial artery	UBERON:0007610	89.41	gold quality
ventricular zone	UBERON:0003053	89.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

65 targeting FGFRL1, 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-4673	100.00	66.64	1490
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 25)

• analysis of FGF18 and FGFR5(FGFRL1) expression in primary endothelial cells and vascular smooth muscle cells (PMID:16019430)
• Screening of 241 different human tumors with the help of a cancer profiling array suggested major alterations in the relative expression of FGFRL1 in ovarian tumors (PMID:16273302)
• The extracellular domain of recombinant FGFRL1 promoted cell adhesion, but not cell spreading. Adhesion was mediated by heparan sulfate glycosaminoglycans located at the cell surface. (PMID:18061161)
• mutant FGFRL1 contributes to the skeletal malformations of the patient (PMID:19056490)
• FGFRL1 is indeed a decoy receptor for FGFs. (PMID:19920134)
• The signaling complex appears to integrate the input from FGFR and EphA4, and release the output signal through FRS2alpha. (PMID:20184660)
• FGFRL1 is capable of inducing syncytium formation of heterologous cells in vitro. (PMID:20851884)
• an important role for miR-210 as a tumor-suppressive microRNA with effects on cancer cell proliferation (PMID:21044961)
• Interaction of FGFRL1 with Spred1 increases the proportion of the receptor at the plasma membrane. (PMID:21616146)
• study identified a novel region of deletion mapping to 4p16.3 in 15 percent of bladder tumors and 24 percent of bladder cancer cell lines; FGFRL1, which maps within this region, was investigated as putative deletion target; average FGFRL1 protein expression was lower in bladder tumors compared to normal tissue, but downregulation was independent from 4p16.3 LOH status (PMID:23775577)
• functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. (PMID:25941324)
• Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 (PMID:26025674)
• FGFRL1 is a cell adhesion protein. (PMID:27220341)
• Both in vitro and in vivo studies determined that miR-210 promoted hepatocellular carcinoma (HCC), angiogenesis, and the corresponding mechanism was identified to be the direct targeting and inhibition of fibroblast growth factor receptor-like 1 (FGFRL1) expression (PMID:27666683)
• FGFRL1 is a transmembrane receptor that can induce the fusion of CHO cells to multinucleated syncytia. This cell fusion activity has been attributed to the extracellular Ig3 domain of the receptor. The Ig3 domain from humans, mice, chicken and fish stimulates fusion of CHO cells, while the Ig3 domain from lancelet and sea urchin does not. (PMID:28596102)
• this study shows FGFRL1 promotes ovarian cancer progression by crosstalk with Hedgehog signaling (PMID:29675438)
• FGFRL1 affects chemoresistance of small-cell lung cancer by modulating the PI3K/Akt pathway via ENO1. (PMID:31957179)
• Fibroblast growth factor receptor-like-1: a new therapeutic target and unfavorable prognostic indicator for rectal adenocarcinoma. (PMID:32098557)
• Lung CSC-derived exosomal miR-210-3p contributes to a pro-metastatic phenotype in lung cancer by targeting FGFRL1. (PMID:32396269)
• Dissecting the Interaction of FGF8 with Receptor FGFRL1. (PMID:33019532)
• [Expression of fibroblast growth factor receptor like 1 protein in oral squamous cell carcinoma and its influence on tumor cell proliferation and migration]. (PMID:33085242)
• Evidence that FGFRL1 contributes to congenital diaphragmatic hernia development in humans. (PMID:33443296)
• FGFRL1 and FGF genes are associated with height, hypertension, and osteoporosis. (PMID:35980984)
• Downregulation of miR-210-3p Attenuates High Glucose-Induced Angiogenesis of Vascular Endothelial Cells via Targeting FGFRL1. (PMID:37062273)
• Aberrant Expression of FGFRL1 in Esophageal Cancer and Its Regulation by miR-107. (PMID:37116156)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgfrl1a	ENSDARG00000032617
mus_musculus	Fgfrl1	ENSMUSG00000008090
rattus_norvegicus	Fgfrl1	ENSRNOG00000024207
drosophila_melanogaster	CG31431	FBGN0051431
caenorhabditis_elegans		WBGENE00022418

Paralogs (2): MCRIP2 (ENSG00000172366), MCRIP1 (ENSG00000225663)

Protein

Protein identifiers

Fibroblast growth factor receptor-like 1 — Q8N441 (reviewed: Q8N441)

Alternative names: FGF homologous factor receptor, FGFR-like protein, Fibroblast growth factor receptor 5

All UniProt accessions (3): Q8N441, D6RBN8, D6REM7

UniProt curated annotations — full annotation on UniProt →

Function. Has a negative effect on cell proliferation.

Subunit / interactions. Interacts with FGF2 with a low affinity.

Subcellular location. Membrane.

Tissue specificity. Expressed preferentially in cartilaginous tissues and pancreas. Highly expressed in the liver, kidney, heart, brain and skeletal muscle. Weakly expressed in the lung, small intestine and spleen.

RefSeq proteins (4): NP_001004356, NP_001004358, NP_001357225, NP_068742 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052615	FGFRL	Family

Pfam: PF07679, PF13927

UniProt features (23 total): glycosylation site 4, compositionally biased region 3, disulfide bond 3, domain 3, topological domain 2, sequence variant 2, region of interest 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N441-F1	72.04	0.29

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 (3): 51–99, 172–221, 268–338

Glycosylation sites (4): 111, 231, 255, 293

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5658623	FGFRL1 modulation of FGFR1 signaling

MSigDB gene sets: 400 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, RNGTGGGC_UNKNOWN, TAATAAT_MIR126, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, WWTAAGGC_UNKNOWN, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, REACTOME_SIGNALING_BY_FGFR, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, SRF_Q5_01, GOBP_CELL_CELL_ADHESION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, SRF_C

GO Biological Process (7): skeletal system development (GO:0001501), heart valve morphogenesis (GO:0003179), negative regulation of cell population proliferation (GO:0008285), ventricular septum morphogenesis (GO:0060412), diaphragm development (GO:0060539), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), fibroblast growth factor receptor signaling pathway (GO:0008543)

GO Molecular Function (4): fibroblast growth factor receptor activity (GO:0005007), heparin binding (GO:0008201), fibroblast growth factor binding (GO:0017134), identical protein binding (GO:0042802)

GO Cellular Component (5): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), transport vesicle (GO:0030133), cell-cell contact zone (GO:0044291), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by FGFR1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
system development	1
heart valve development	1
anatomical structure morphogenesis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
ventricular septum development	1
cardiac septum morphogenesis	1
skeletal muscle organ development	1
respiratory system development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
transmembrane receptor protein tyrosine kinase activity	1
fibroblast growth factor receptor signaling pathway	1
fibroblast growth factor binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
growth factor binding	1
protein binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cytoplasmic vesicle	1
cell-cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGFRL1	FGF8	P55075	731
FGFRL1	FGF1	P05230	663
FGFRL1	FGF2	P09038	661
FGFRL1	FGF18	O76093	659
FGFRL1	FGF13	Q92913	657
FGFRL1	FGF10	O15520	647
FGFRL1	FGF9	P31371	640
FGFRL1	FGF7	P21781	635
FGFRL1	FGF20	Q9NP95	633
FGFRL1	FGF12	P61328	633
FGFRL1	FGF16	O43320	627
FGFRL1	FGF22	Q9HCT0	619
FGFRL1	FGF3	P11487	618
FGFRL1	FGF4	P08620	614
FGFRL1	FGF17	O60258	609

IntAct

36 interactions, top by confidence:

A	B	Type	Score
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
TMED2	ATP9A	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
TRIM44	ODAD3	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
GP6	FGFRL1	psi-mi:“MI:0915”(physical association)	0.400
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CD44	TCAF2	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
SDC2	METTL8	psi-mi:“MI:0914”(association)	0.350
FGFRL1	BACH1	psi-mi:“MI:0914”(association)	0.350
CLEC4A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
FGFRL1	AP3B1	psi-mi:“MI:0914”(association)	0.350
TNFRSF1B	MAP3K7	psi-mi:“MI:0914”(association)	0.350
KRT35	TIMP1	psi-mi:“MI:0914”(association)	0.350
FGFRL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SDC2	ELAPOR2	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350
KLRG2	HS3ST1	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): FGFRL1 (Affinity Capture-RNA), FGFRL1 (Affinity Capture-MS), FGFRL1 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), FGFRL1 (Affinity Capture-MS), BACH1 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), FGFRL1 (Affinity Capture-MS), FGFRL1 (Affinity Capture-MS), VPRBP (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), PPP1R15B (Affinity Capture-MS), FGFRL1 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), ANGEL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, D3YX43, D3YZF7, O08852, O14931, O15533, O43157, O70394, O70540, O75074, O88204, P01880, P0C788, P18627, P59383, P61484, P70289, Q15109, Q28173, Q5BK54, Q5DID0, Q5RKR3, Q5TJE4, Q61790, Q61826, Q62151, Q63495, Q64612, Q6PZD2, Q7TQH7, Q7Z4F1, Q80W87, Q86T13, Q86VR7, Q8C310, Q8CB67, Q8CJH3, Q8IZF5, Q8MJ02, Q8N441

Diamond homologs: A0A087WV53, A1KZ92, A2AJ76, A4IFW2, A4IGL7, A6NDA9, B0BNK7, B0V2N1, D2HFT7, D3YXG0, D4A1J9, D4ABX8, F1NWE3, G5EG78, O15146, O73775, O75325, O94898, P07722, P15364, P20916, P20917, P23468, P43146, P48960, P53813, P70193, P70211, Q03142, Q08761, Q08879, Q13332, Q13449, Q1ENI8, Q1RMS4, Q1WIM1, Q21038, Q24372, Q26474, Q2Q421

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	209
Likely benign	139
Benign	21

Top pathogenic / likely-pathogenic (0)

SpliceAI

1923 predictions. Top by Δscore:

Variant	Effect	Δscore
4:1012564:GGT:G	donor_loss	1.0000
4:1012565:G:GA	donor_loss	1.0000
4:1012566:T:A	donor_loss	1.0000
4:1022200:CA:C	acceptor_loss	1.0000
4:1022201:A:AG	acceptor_gain	1.0000
4:1022202:G:GG	acceptor_gain	1.0000
4:1022471:GCTGG:G	donor_gain	1.0000
4:1022472:CTGG:C	donor_loss	1.0000
4:1022473:TGG:T	donor_loss	1.0000
4:1022474:GG:G	donor_gain	1.0000
4:1022475:GG:G	donor_gain	1.0000
4:1022476:G:GG	donor_gain	1.0000
4:1022476:G:T	donor_loss	1.0000
4:1023717:GTGGG:G	donor_gain	1.0000
4:1023809:C:G	acceptor_gain	1.0000
4:1023815:A:AG	acceptor_gain	1.0000
4:1023815:AGCAC:A	acceptor_gain	1.0000
4:1023816:G:GT	acceptor_gain	1.0000
4:1023816:GCAC:G	acceptor_gain	1.0000
4:1023816:GCACG:G	acceptor_gain	1.0000
4:1024097:GATCC:G	donor_gain	1.0000
4:1024099:TCC:T	donor_gain	1.0000
4:1024100:CCG:C	donor_loss	1.0000
4:1024101:CG:C	donor_loss	1.0000
4:1024102:G:GG	donor_gain	1.0000
4:1024102:GT:G	donor_loss	1.0000
4:1024103:T:G	donor_loss	1.0000
4:1024104:GAGT:G	donor_loss	1.0000
4:1010087:G:GT	donor_gain	0.9900
4:1010087:G:T	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000129345 (4:1017283 C>G,T), RS1000184487 (4:1023125 C>G,T), RS1000284494 (4:1010887 T>C), RS1000397629 (4:1014383 C>T), RS1000859639 (4:1009332 G>A), RS1000886618 (4:1011982 C>T), RS1000973441 (4:1009499 G>A), RS1000981403 (4:1025051 A>C), RS1001022076 (4:1014247 A>G), RS1001177825 (4:1013851 G>A), RS1001355112 (4:1012187 C>G,T), RS1001395827 (4:1026278 A>T), RS1001511673 (4:1021895 T>A,C), RS1001585276 (4:1022059 G>A,C), RS1001642739 (4:1012841 T>C)

Disease associations

OMIM: gene MIM:605830 | disease phenotypes: MIM:194190, MIM:142340

GenCC curated gene-disease

Mondo (3): Wolf-Hirschhorn syndrome (MONDO:0008684), microcephaly (MONDO:0001149), congenital diaphragmatic hernia (MONDO:0005711)

Orphanet (2): Wolf-Hirschhorn syndrome (Orphanet:280), Congenital diaphragmatic hernia (Orphanet:2140)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000119	Abnormality of the genitourinary system
HP:0000151	Aplasia of the uterus
HP:0000175	Cleft palate
HP:0000188	Short upper lip
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000377	Abnormal pinna morphology
HP:0000384	Preauricular skin tag
HP:0000402	Stenosis of the external auditory canal
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000465	Webbed neck
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000558	Rieger anomaly
HP:0000612	Iris coloboma
HP:0000639	Nystagmus

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001762_84	Obesity-related traits	4.000000e-06
GCST002276_20	Bone mineral density	5.000000e-12
GCST003129_30	Primary biliary cholangitis	9.000000e-12
GCST004611_56	High light scatter reticulocyte count	6.000000e-10
GCST004612_63	High light scatter reticulocyte percentage of red cells	9.000000e-10
GCST005795_18	Femoral neck bone mineral density	4.000000e-10
GCST006288_203	Heel bone mineral density	3.000000e-32
GCST006288_204	Heel bone mineral density	2.000000e-13
GCST006288_310	Heel bone mineral density	1.000000e-19
GCST006288_311	Heel bone mineral density	2.000000e-12
GCST006288_518	Heel bone mineral density	6.000000e-52
GCST006288_519	Heel bone mineral density	8.000000e-24
GCST006423_17	Fracture	2.000000e-08
GCST006979_318	Heel bone mineral density	2.000000e-64
GCST006979_319	Heel bone mineral density	7.000000e-99
GCST006979_320	Heel bone mineral density	4.000000e-73
GCST006980_2	Fracture	3.000000e-24
GCST006980_3	Fracture	2.000000e-14
GCST008707_2	Occipital lobe volume	6.000000e-09
GCST90000025_252	Appendicular lean mass	9.000000e-27
GCST90002385_243	High light scatter reticulocyte count	2.000000e-10
GCST90002386_572	High light scatter reticulocyte percentage of red cells	1.000000e-10
GCST90002405_33	Reticulocyte count	1.000000e-11
GCST90002406_83	Reticulocyte fraction of red cells	4.000000e-12
GCST90011900_86	Serum alkaline phosphatase levels	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0007986	reticulocyte count
EFO:0007785	femoral neck bone mineral density
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D054877	Wolf-Hirschhorn Syndrome	C16.131.077.944; C16.131.260.985; C16.320.180.985

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases oxidation, increases expression, decreases expression, affects cotreatment, increases abundance	3
Arsenic	increases expression, affects methylation, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation, affects methylation	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
lead acetate	increases expression	1
terbufos	increases methylation	1
sodium arsenite	increases abundance, increases expression	1
perfluorooctanoic acid	decreases expression, affects cotreatment	1
zinc chromate	decreases expression, increases abundance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Cosmetics	decreases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	increases expression	1
Flame Retardants	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Parathion	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05213676	PHASE4	RECRUITING	De-implementing Inhaled Nitric Oxide for Congenital Diaphragmatic Hernia
NCT07247240	PHASE4	NOT_YET_RECRUITING	Efficacy of Inhaled Nitric Oxide in Congenital Diaphragmatic Hernia
NCT00257946	PHASE3	TERMINATED	Type of Material in Repair of Congenital Diaphragmatic Hernia
NCT03861182	PHASE3	TERMINATED	Contribution of PRF in CDH in Children With Prothetic Patch Closure
NCT06946576	PHASE3	NOT_YET_RECRUITING	Safety and Efficacy of Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia
NCT07187206	PHASE3	RECRUITING	Safety and Efficacy of FETO in CDH Phase III
NCT00373438	PHASE2	UNKNOWN	Fetoscopic Tracheal Balloon Occlusion in Left Diaphragmatic Hernia
NCT00966823	PHASE2	TERMINATED	Fetal Tracheal Balloon Study in Diaphragmatic Hernia
NCT01302977	PHASE2	UNKNOWN	Fetal Tracheal Occlusion in Severe Diaphragmatic Hernia: a Randomized Trial
NCT01731509	PHASE2	UNKNOWN	Early FETO for Severe Congenital Diaphragmatic Hernia
NCT02875860	PHASE2	COMPLETED	‘TOTAL’ (Tracheal Occlusion To Accelerate Lung Growth) Trial
NCT02951130	PHASE2	COMPLETED	Milrinone in Congenital Diaphragmatic Hernia
NCT05201144	PHASE2	RECRUITING	A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)
NCT03526588	PHASE1	TERMINATED	Umbilical Cord Blood Mononuclear Cells for Hypoxic Neurologic Injury in Infants With Congenital Diaphragmatic Hernia (CDH)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.
NCT01240057	PHASE2/PHASE3	COMPLETED	Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia
NCT00371241	Not specified	COMPLETED	Antibody Secreting Cell and Cyotokine Profiles in Neonates on ECMO
NCT00373763	Not specified	WITHDRAWN	Fetoscopic Tracheal Balloon Occlusion in Unborns With Severe Congenital Diaphragmatic Hernia - EUROTRIAL I
NCT00763737	Not specified	COMPLETED	Fetal Surgery for Moderate Left Sided Congenital Diaphragmatic Hernia.
NCT00881660	Not specified	COMPLETED	Fetal Endotracheal Occlusion (FETO) in Severe and Extremely Severe Congenital Diaphragmatic Hernia
NCT00950118	Not specified	RECRUITING	Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science
NCT01098929	Not specified	UNKNOWN	Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia
NCT01155830	Not specified	COMPLETED	Inflammatory Cytokine Quantification in Infants