GLDN

Summary

GLDN (gliomedin, HGNC:29514) is a protein-coding gene on chromosome 15q21.2, encoding Gliomedin (Q6ZMI3). Ligand for NRCAM and NFASC/neurofascin that plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons.

This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy.

Source: NCBI Gene 342035 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lethal congenital contracture syndrome 11 (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 192 total — 6 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 36
• MANE Select transcript: NM_181789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29514
Approved symbol	GLDN
Name	gliomedin
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Aliases	CRG-L2, CLOM, colmedin, UNC-122
Ensembl gene	ENSG00000186417
Ensembl biotype	protein_coding
OMIM	608603
Entrez	342035

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 5 retained_intron

ENST00000335449, ENST00000396399, ENST00000464150, ENST00000558286, ENST00000558426, ENST00000559317, ENST00000560215, ENST00000560690, ENST00000561194, ENST00000857823

RefSeq mRNA: 2 — MANE Select: NM_181789 NM_001330297, NM_181789

CCDS: CCDS10140, CCDS81882

Canonical transcript exons

ENST00000335449 — 10 exons

Exon	Start	End
ENSE00001337070	51401593	51401743
ENSE00001337071	51400373	51400498
ENSE00001337072	51400192	51400275
ENSE00001337133	51397470	51397598
ENSE00001337135	51394835	51394981
ENSE00001337136	51383785	51383892
ENSE00001431029	51404277	51408000
ENSE00001632503	51341655	51342047
ENSE00003464877	51383436	51383453
ENSE00003555062	51377449	51377500

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 99.12.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1303 / max 434.1932, expressed in 298 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146633	2.3543	250
146638	0.4369	104
146636	0.2227	79
146637	0.0552	32
146635	0.0391	6
146639	0.0159	7
146634	0.0062	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.12	gold quality
trigeminal ganglion	UBERON:0001675	98.76	gold quality
pons	UBERON:0000988	98.53	gold quality
subthalamic nucleus	UBERON:0001906	98.28	gold quality
dorsal root ganglion	UBERON:0000044	97.98	gold quality
endothelial cell	CL:0000115	97.97	gold quality
sural nerve	UBERON:0015488	97.96	gold quality
corpus callosum	UBERON:0002336	97.67	gold quality
medulla oblongata	UBERON:0001896	97.61	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.56	gold quality
lateral globus pallidus	UBERON:0002476	97.38	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.03	gold quality
globus pallidus	UBERON:0001875	96.89	gold quality
ventral tegmental area	UBERON:0002691	96.82	gold quality
superior vestibular nucleus	UBERON:0007227	96.82	gold quality
medial globus pallidus	UBERON:0002477	96.63	gold quality
upper arm skin	UBERON:0004263	95.54	gold quality
substantia nigra pars compacta	UBERON:0001965	95.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.63	gold quality
spinal cord	UBERON:0002240	93.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.75	gold quality
pancreatic ductal cell	CL:0002079	92.87	silver quality
midbrain	UBERON:0001891	92.86	gold quality
skin of hip	UBERON:0001554	92.33	gold quality
substantia nigra	UBERON:0002038	92.28	gold quality
layer of synovial tissue	UBERON:0007616	91.83	gold quality
parietal lobe	UBERON:0001872	91.14	gold quality
postcentral gyrus	UBERON:0002581	90.84	gold quality
lower lobe of lung	UBERON:0008949	90.45	gold quality
tibial nerve	UBERON:0001323	90.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1039.02
E-ANND-3	yes	4.98
E-ENAD-17	no	58.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting GLDN, 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-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4766-5P	99.75	69.23	2662

Literature-anchored findings (GeneRIF, showing 5)

• Fibronectin type III-like domains of neurofascin-186 protein mediate gliomedin binding and its clustering at the developing nodes of Ranvier (PMID:22009740)
• gliomedin, NF186, and contactin are novel target antigens in Guillain-Barre syndrome (PMID:22462667)
• data indicate that mutations of GLDN or CNTNAP1 (MIM: 616286), encoding essential components of the nodes of Ranvier and paranodes, respectively, lead to inherited nodopathies, a distinct disease entity among peripheral neuropathies (PMID:27616481)
• Our findings expand the genotypic and phenotypic spectrum of LCCS11 and demonstrate that the condition may not necessarily be lethal in the neonatal period. (PMID:28726266)
• The latest FADS: Functional analysis of GLDN patient variants and classification of GLDN-associated AMC as a type of viable fetal akinesia deformation sequence. (PMID:32812332)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gldn	ENSDARG00000061576
mus_musculus	Gldn	ENSMUSG00000046167
rattus_norvegicus	Gldn	ENSRNOG00000024082

Paralogs (9): MYOC (ENSG00000034971), OLFM4 (ENSG00000102837), OLFM2 (ENSG00000105088), OLFML3 (ENSG00000116774), OLFM3 (ENSG00000118733), OLFM1 (ENSG00000130558), OLFML2B (ENSG00000162745), OLFML1 (ENSG00000183801), OLFML2A (ENSG00000185585)

Protein

Protein identifiers

Gliomedin — Q6ZMI3 (reviewed: Q6ZMI3)

All UniProt accessions (3): A0A087X220, Q6ZMI3, H0YM22

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for NRCAM and NFASC/neurofascin that plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Mediates interaction between Schwann cell microvilli and axons via its interactions with NRCAM and NFASC. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters. Required, together with NRCAM, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier.

Subunit / interactions. Homotrimer (via collagen-like domains). Interacts with NRCAM and NFASC/neurofascin. Interaction with glial NRCAM enhances interaction with axonal NFASC. Interacts with MYOC.

Subcellular location. Cell membrane. Cell projection. Axon Secreted. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Specifically expressed in spinal cord, brain, placenta and sciatic nerve. More abundant in peripheral than central nervous system.

Post-translational modifications. N-glycosylated. Proteolytic processing by a furin-like protease causes shedding of the ectodomain. Further cleavage by BMP1 releases the olfactomedin-like domain.

Disease relevance. Lethal congenital contracture syndrome 11 (LCCS11) [MIM:617194] A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The olfactomedin-like domain mediates NFASC/neurofascin and NRCAM binding.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMI3-1	1	yes
Q6ZMI3-2	2

RefSeq proteins (2): NP_001317226, NP_861454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003112	Olfac-like_dom	Domain
IPR008160	Collagen	Repeat
IPR050605	Olfactomedin-like_domain	Family

Pfam: PF01391, PF02191

UniProt features (57 total): strand 21, glycosylation site 5, sequence variant 5, turn 5, compositionally biased region 4, helix 3, domain 3, chain 2, site 2, topological domain 2, region of interest 2, splice variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5YBY	X-RAY DIFFRACTION	1.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMI3-F1	74.36	0.46

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 (2): 94–95 (cleavage; by furin-like protease); 280–281 (cleavage; by bmp1)

Glycosylation sites (5): 130, 329, 357, 378, 464

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 179 (showing top): GOCC_COLLAGEN_TRIMER, GOBP_NEURON_MATURATION, GOCC_CELL_SURFACE, SABATES_COLORECTAL_ADENOMA_SIZE_DN, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, AAAYRNCTG_UNKNOWN, GOBP_CELL_CELL_ADHESION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, OCT1_03, WTGAAAT_UNKNOWN, GOBP_NEURONAL_ION_CHANNEL_CLUSTERING, LIAO_METASTASIS, SABATES_COLORECTAL_ADENOMA_DN

GO Biological Process (6): signal transduction (GO:0007165), microvillus organization (GO:0032528), clustering of voltage-gated sodium channels (GO:0045162), nervous system development (GO:0007399), cell differentiation (GO:0030154), heterotypic cell-cell adhesion (GO:0034113)

GO Molecular Function (1): protein binding involved in heterotypic cell-cell adhesion (GO:0086080)

GO Cellular Component (9): collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), axon (GO:0030424), extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
plasma membrane bounded cell projection organization	1
neuronal ion channel clustering	1
system development	1
cellular developmental process	1
cell-cell adhesion	1
heterotypic cell-cell adhesion	1
cell-cell adhesion mediator activity	1
protein-containing complex	1
membrane	1
cell periphery	1
neuron projection	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLDN	NFASC	O94856	998
GLDN	NRCAM	Q92823	996
GLDN	SPTBN4	Q9H254	798
GLDN	CNTNAP1	P78357	729
GLDN	CNTN1	Q12860	669
GLDN	ANK3	Q12955	645
GLDN	HSPG2	P98160	578
GLDN	MYOC	Q99972	557
GLDN	TIPE3	Q5GJ75	540
GLDN	HAPLN2	Q9GZV7	527
GLDN	GPM6B	Q13491	505
GLDN	CNTN2	P78432	476
GLDN	BCAN	Q96GW7	460
GLDN	KCNQ2	O43526	452
GLDN	DRP2	Q13474	451

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CLU	GLDN	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A2A699, A2BD09, A4IIT5, A5D7T4, A6QLD2, A8MVW0, O35764, O43278, O70624, O95502, O95897, P35054, P51693, Q03157, Q2PT31, Q3UPI1, Q3UZZ4, Q3V1G4, Q568Y7, Q594P2, Q5QQ37, Q66H86, Q68BL7, Q68BL8, Q6AYE5, Q6P7B4, Q6UWH4, Q6UWY5, Q6ZMI3, Q701R2, Q701R3, Q701R4, Q766D5, Q76KP1, Q80WL1, Q863A3, Q866N2, Q86VZ4, Q8BHP7, Q8BM13

Diamond homologs: A2BD09, A4IIT5, A6QLD2, B0BNI5, B5MFE9, O70624, O88917, O88923, O88998, O94910, O95490, O95897, O97817, O97827, O97831, P63056, P63057, Q0P3W2, Q0V9V5, Q0VCP3, Q25C36, Q29RB4, Q2PT31, Q3V1G4, Q568Y7, Q594P2, Q62609, Q66H86, Q68BL7, Q68BL8, Q6UWY5, Q6ZMI3, Q80TR1, Q80TS3, Q80WL1, Q863A3, Q866N2, Q8BHP7, Q8BK62, Q8BM13

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GLDN	“up-regulates quantity”	ANK3	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	19
Uncertain significance	100
Likely benign	23
Benign	30

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1711396	GRCh37/hg19 15q21.2(chr15:51633882-51696951)x1	Pathogenic
268104	NM_181789.4(GLDN):c.758del (p.Pro253fs)	Pathogenic
268107	NM_181789.4(GLDN):c.1240C>T (p.Arg414Ter)	Pathogenic
268108	NM_181789.4(GLDN):c.541+1G>A	Pathogenic
3382965	NM_181789.4(GLDN):c.139dup (p.Ala47fs)	Pathogenic
523974	NM_181789.4(GLDN):c.330del (p.Asp110fs)	Pathogenic
1175345	NM_181789.4(GLDN):c.82G>C (p.Ala28Pro)	Likely pathogenic
2630091	NM_181789.4(GLDN):c.689-2A>G	Likely pathogenic
2663883	NM_181789.4(GLDN):c.817+1G>A	Likely pathogenic
268105	NM_181789.4(GLDN):c.1423G>C (p.Ala475Pro)	Likely pathogenic
268106	NM_181789.4(GLDN):c.95C>A (p.Ala32Glu)	Likely pathogenic
268109	NM_181789.4(GLDN):c.1435C>T (p.Arg479Ter)	Likely pathogenic
2690612	NM_181789.4(GLDN):c.1347dup (p.Ala450fs)	Likely pathogenic
3254992	NM_181789.4(GLDN):c.1507C>T (p.Gln503Ter)	Likely pathogenic
3336674	NM_181789.4(GLDN):c.1525_1529del (p.Asp509fs)	Likely pathogenic
3382964	NM_181789.4(GLDN):c.1143_1144del (p.Tyr382fs)	Likely pathogenic
449987	NM_181789.4(GLDN):c.1436G>C (p.Arg479Pro)	Likely pathogenic
452117	NM_181789.4(GLDN):c.1179-2A>G	Likely pathogenic
4845823	NM_181789.4(GLDN):c.1423G>A (p.Ala475Thr)	Likely pathogenic
807423	NM_181789.4(GLDN):c.86T>C (p.Leu29Pro)	Likely pathogenic
813290	NM_181789.4(GLDN):c.1093C>T (p.Leu365Phe)	Likely pathogenic
813924	NM_181789.4(GLDN):c.59T>C (p.Leu20Pro)	Likely pathogenic
916579	NM_181789.4(GLDN):c.385_392del (p.Cys129fs)	Likely pathogenic
974889	NM_181789.4(GLDN):c.1028-2A>T	Likely pathogenic
978637	NM_181789.4(GLDN):c.1027G>A (p.Gly343Ser)	Likely pathogenic

SpliceAI

2128 predictions. Top by Δscore:

Variant	Effect	Δscore
15:51383777:T:TA	acceptor_gain	1.0000
15:51383780:TGCA:T	acceptor_loss	1.0000
15:51383781:GCA:G	acceptor_loss	1.0000
15:51383783:A:AG	acceptor_gain	1.0000
15:51383783:A:T	acceptor_loss	1.0000
15:51383784:G:GA	acceptor_gain	1.0000
15:51383784:GGAC:G	acceptor_gain	1.0000
15:51383884:G:GT	donor_gain	1.0000
15:51383885:A:T	donor_gain	1.0000
15:51383889:A:AG	donor_gain	1.0000
15:51383889:A:G	donor_gain	1.0000
15:51400271:AGCAG:A	donor_loss	1.0000
15:51400272:GCAGG:G	donor_loss	1.0000
15:51400273:CAG:C	donor_loss	1.0000
15:51400274:AG:A	donor_loss	1.0000
15:51400275:GGT:G	donor_loss	1.0000
15:51400276:G:GA	donor_loss	1.0000
15:51400277:T:A	donor_loss	1.0000
15:51400367:T:A	acceptor_gain	1.0000
15:51400368:G:A	acceptor_gain	1.0000
15:51400368:GGCA:G	acceptor_loss	1.0000
15:51400369:GCAG:G	acceptor_loss	1.0000
15:51400370:CAGA:C	acceptor_loss	1.0000
15:51400371:A:AG	acceptor_gain	1.0000
15:51400372:G:GG	acceptor_gain	1.0000
15:51400372:GA:G	acceptor_gain	1.0000
15:51400372:GAA:G	acceptor_gain	1.0000
15:51400372:GAAT:G	acceptor_gain	1.0000
15:51400372:GAATC:G	acceptor_gain	1.0000
15:51400497:AGGTA:A	donor_loss	1.0000

AlphaMissense

3574 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:51404363:A:T	K422I	0.995
15:51404543:T:C	L482P	0.995
15:51404549:T:A	V484D	0.995
15:51400438:T:A	W323R	0.994
15:51400438:T:C	W323R	0.994
15:51400492:T:C	F341L	0.994
15:51400494:T:A	F341L	0.994
15:51400494:T:G	F341L	0.994
15:51404446:G:C	A450P	0.994
15:51404545:T:G	Y483D	0.994
15:51401712:T:G	Y383D	0.993
15:51404525:T:C	F476S	0.993
15:51404364:A:C	K422N	0.992
15:51404364:A:T	K422N	0.992
15:51404692:T:A	W532R	0.991
15:51404692:T:C	W532R	0.991
15:51400432:G:T	G321W	0.990
15:51400477:T:A	W336R	0.989
15:51400477:T:C	W336R	0.989
15:51401677:G:A	G371D	0.989
15:51404497:T:G	Y467D	0.989
15:51404694:G:C	W532C	0.989
15:51404694:G:T	W532C	0.989
15:51401602:T:A	V346D	0.988
15:51401677:G:T	G371V	0.988
15:51404401:T:A	W435R	0.988
15:51404401:T:C	W435R	0.988
15:51400433:G:A	G321E	0.987
15:51404522:C:A	A475D	0.987
15:51404684:T:C	L529S	0.987

dbSNP variants (sampled 300 via entrez): RS1000021751 (15:51368350 G>A), RS1000025062 (15:51405379 T>G), RS1000118194 (15:51399382 T>C,G), RS1000164655 (15:51344045 C>T), RS1000197517 (15:51364479 A>G), RS1000229743 (15:51347503 C>T), RS1000254726 (15:51385554 A>C), RS1000260289 (15:51379349 C>T), RS1000326495 (15:51384372 G>T), RS1000344850 (15:51405117 G>C,T), RS1000401149 (15:51350620 G>A,T), RS1000402465 (15:51411248 T>C), RS1000418607 (15:51363083 A>G), RS1000436208 (15:51341340 C>A), RS1000551913 (15:51380138 G>A)

Disease associations

OMIM: gene MIM:608603 | disease phenotypes: MIM:617194, MIM:617468, MIM:208150, MIM:613546

GenCC curated gene-disease

Disease	Classification	Inheritance
lethal congenital contracture syndrome 11	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
lethal congenital contracture syndrome 11	Definitive	AR

Mondo (6): lethal congenital contracture syndrome 11 (MONDO:0014965), polyhydramnios (MONDO:0004585), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), congenital contractures (MONDO:0022823), aromatase deficiency (MONDO:0013301)

Orphanet (3): Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994), Aromatase deficiency (Orphanet:91)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000278	Retrognathia
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000476	Cystic hygroma
HP:0001059	Pterygium
HP:0001262	Excessive daytime somnolence
HP:0001305	Dandy-Walker malformation
HP:0001371	Flexion contracture
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001776	Bilateral talipes equinovarus
HP:0001989	Fetal akinesia sequence
HP:0002089	Pulmonary hypoplasia
HP:0002093	Respiratory insufficiency
HP:0002304	Akinesia
HP:0002375	Hypokinesia
HP:0002650	Scoliosis
HP:0002804	Arthrogryposis multiplex congenita
HP:0002828	Multiple joint contractures
HP:0002987	Elbow flexion contracture
HP:0003577	Congenital onset
HP:0003700	Generalized amyotrophy
HP:0005245	Intestinal hypoplasia
HP:0005280	Depressed nasal bridge

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003196_1	Calcaneal bone ultrasound measurement (speed of sound)	2.000000e-09
GCST006979_1023	Heel bone mineral density	5.000000e-20
GCST008839_16	Height	2.000000e-10
GCST012145_6	Ferritin levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004459	ferritin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006831	Polyhydramnios	C12.050.703.610
C537436	Aromatase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6493497	CYP19A1, GLDN	3	5.00	2	exemestane;letrozole;anastrozole;exemestane;letrozole
rs7176005	CYP19A1, GLDN	3	3.00	1	exemestane

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
diethylene glycol	affects response to substance	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC668394	increases expression	1
Vorinostat	increases expression	1
Glyphosate	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Naled	affects expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00236340	Not specified	COMPLETED	Syringe or Continuous Amnioreduction for Symptomatic Polyhydramnios. A Prospective Randomized Study.
NCT03277417	Not specified	UNKNOWN	Does Amniotic Fluid Index Affect the Fetal Cardiac Performance?
NCT04497532	Not specified	UNKNOWN	Influence of Diet on Pregnancy With Polyhydramnios
NCT05043753	Not specified	RECRUITING	Fetal gRowth AbnorMality dEtection Trial
NCT05059093	Not specified	COMPLETED	Developing and Testing AI Models for Fetal Biometry and Amniotic Volume Assessment in Fetal Ultrasound Scans.
NCT07067593	Not specified	NOT_YET_RECRUITING	Amnioreduction in Polyhydramnios
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3