GPC6

Summary

GPC6 (glypican 6, HGNC:4454) is a protein-coding gene on chromosome 13q31.3-q32.1, encoding Glypican-6 (Q9Y625). Cell surface proteoglycan that bears heparan sulfate.

The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1.

Source: NCBI Gene 10082 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive omodysplasia (Strong, GenCC)
• GWAS associations: 38
• Clinical variants (ClinVar): 383 total — 10 pathogenic
• Phenotypes (HPO): 52
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_005708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4454
Approved symbol	GPC6
Name	glypican 6
Location	13q31.3-q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183098
Ensembl biotype	protein_coding
OMIM	604404
Entrez	10082

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377047

RefSeq mRNA: 1 — MANE Select: NM_005708 NM_005708

CCDS: CCDS9469

Canonical transcript exons

ENST00000377047 — 9 exons

Exon	Start	End
ENSE00001294212	94398466	94398641
ENSE00001298357	94305980	94306123
ENSE00001299414	94027729	94027894
ENSE00001301341	94382414	94382550
ENSE00001302924	93830154	93830545
ENSE00001314072	93545263	93545421
ENSE00001472611	94403015	94408020
ENSE00001625889	94286349	94286479
ENSE00001657234	93226807	93227616

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.9786 / max 970.4538, expressed in 1299 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135643	11.5862	1220
135644	8.4997	1129
135646	2.9091	877
135647	2.0406	749
135652	1.4435	603
135654	1.2663	717
135650	0.8749	556
135653	0.8005	490
135648	0.7622	435
135645	0.5877	341

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	98.68	gold quality
tibia	UBERON:0000979	96.83	gold quality
vena cava	UBERON:0004087	93.09	gold quality
superficial temporal artery	UBERON:0001614	91.36	gold quality
kidney epithelium	UBERON:0004819	90.46	gold quality
adrenal tissue	UBERON:0018303	90.33	gold quality
saphenous vein	UBERON:0007318	90.02	gold quality
seminal vesicle	UBERON:0000998	89.68	gold quality
epithelial cell of pancreas	CL:0000083	89.48	silver quality
dorsal root ganglion	UBERON:0000044	89.14	gold quality
layer of synovial tissue	UBERON:0007616	87.99	gold quality
caput epididymis	UBERON:0004358	87.41	gold quality
ventricular zone	UBERON:0003053	87.40	gold quality
trigeminal ganglion	UBERON:0001675	85.88	gold quality
gall bladder	UBERON:0002110	85.28	gold quality
pigmented layer of retina	UBERON:0001782	84.12	gold quality
liver	UBERON:0002107	83.74	gold quality
colonic epithelium	UBERON:0000397	83.06	gold quality
popliteal artery	UBERON:0002250	82.48	gold quality
tibial artery	UBERON:0007610	82.47	gold quality
ganglionic eminence	UBERON:0004023	82.12	gold quality
synovial joint	UBERON:0002217	81.81	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.92	silver quality
caecum	UBERON:0001153	80.79	gold quality
islet of Langerhans	UBERON:0000006	80.61	gold quality
urinary bladder	UBERON:0001255	80.60	gold quality
aorta	UBERON:0000947	80.13	gold quality
mammary duct	UBERON:0001765	79.97	gold quality
epithelium of mammary gland	UBERON:0003244	79.78	gold quality
skin of hip	UBERON:0001554	79.65	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3248.15
E-CURD-11	yes	98.40
E-HCAD-10	yes	15.63
E-GEOD-81608	yes	14.94
E-ANND-3	yes	10.35
E-ENAD-27	yes	9.82
E-HCAD-25	yes	9.07
E-MTAB-6678	yes	4.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFATC1, NFATC2, NFATC3, NFATC4

miRNA regulators (miRDB)

447 targeting GPC6, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• Mutations in the heparan-sulfate proteoglycan glypican 6 impair endochondral ossification and cause recessive omodysplasia (PMID:19481194)
• a reduction in GPC6 mRNA in retinoblastoma is associated with the non-random allelic loss at 13q31 that could contribute to RB development. (PMID:19726429)
• GPC6 promotes invasive migration by inhibition of canonical beta-catenin and Wnt signalling, and up-regulation of non-canonical Wnt5A signalling leading to the activation of JNK and p38 MAPK. (PMID:21871017)
• Extracellular matrix proteins expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line. (PMID:24804215)
• Thus, GPC6 and TMEM132D may serve as predictors of CD8+ T-lymphocyte infiltration and as favorable prognostic markers in early stage ovarian cancer with important consequences for diagnosis. (PMID:26448945)
• GPC6 rs4773724 was associated with a decreased risk of LDH in allele model (OR = 0.82, 95% CI: 0.68-0.98, p = 0.026), whereas rs1008993 increased the LDH risk (OR = 1.34, 95% CI: 1.05-1.71, p = 0.020). rs4773724 and rs9523981 were associated with susceptibility of LDH among individuals whose age are less than 45. And rs1008993 was associated with increased LDH risk in males. (PMID:31111662)
• findings identified GPC6 as an early biomarker for melanoma metastatic progression, one that can be regulated by miR-509-3p. (PMID:31199813)
• Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial-mesenchymal transition of gastric cancer cells. (PMID:32478377)
• Can Glypican-6 Level Predict Ejection Fraction Decline After Myocardial Infarction? (PMID:33094648)
• TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6. (PMID:33762006)
• Prognostic value of GPC5 polymorphism rs2352028 and clinical characteristics in Chinese lung cancer patients. (PMID:36165234)
• Five siblings expand the spectrum of GPC6-related skeletal dysplasia. (PMID:37353964)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpc6a	ENSDARG00000103156
danio_rerio	gpc6b	ENSDARG00000104219
mus_musculus	Gpc6	ENSMUSG00000058571
rattus_norvegicus	Gpc6	ENSRNOG00000062503
drosophila_melanogaster	dlp	FBGN0041604

Paralogs (5): GPC1 (ENSG00000063660), GPC4 (ENSG00000076716), GPC3 (ENSG00000147257), GPC5 (ENSG00000179399), GPC2 (ENSG00000213420)

Protein

Protein identifiers

Glypican-6 — Q9Y625 (reviewed: Q9Y625)

All UniProt accessions (1): Q9Y625

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Enhances migration and invasion of cancer cells through WNT5A signaling.

Subcellular location. Cell membrane Secreted. Extracellular space.

Tissue specificity. Widely expressed. High expression in fetal kidney and lung and lower expressions in fetal liver and brain. In adult tissues, very abundant in ovary, high levels also observed in liver, kidney, small intestine and colon. Not detected in peripheral blood leukocytes. Detected in breast cancer cells (at protein level).

Disease relevance. Omodysplasia 1 (OMOD1) [MIM:258315] A rare autosomal recessive skeletal dysplasia characterized by facial dysmorphism and severe congenital micromelia with shortening and distal tapering of the humeri and femora, to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin. The disease is caused by variants affecting the gene represented in this entry. Point mutations leading to protein truncation, as well as larger genomic rearrangements resulting in exon deletions, have been found in family segregating omodysplasia type 1. All mutations identified in individuals affected by omodysplasia could lead to the absence of a functional protein, the mutant RNAs being suspected to be nonsense-mediated mRNA decay (NMD) targets. Even if the mRNA escapes NMD and is translated, all mutations are expected to disrupt the three-dimensional protein structure and often to abolish multiple highly conserved cysteine residues.

Induction. Expression is induced by NFATC2.

Similarity. Belongs to the glypican family.

RefSeq proteins (1): NP_005699* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001863	Glypican	Family
IPR019803	Glypican_CS	Conserved_site

Pfam: PF01153

UniProt features (10 total): chain 2, region of interest 2, signal peptide 1, propeptide 1, compositionally biased region 1, lipid moiety-binding region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y625-F1	82.67	0.70

Functional residue map

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

Post-translational modifications (1): 529

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 428 (showing top): GOCC_CELL_SURFACE, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, RIGGI_EWING_SARCOMA_PROGENITOR_DN, AACTTT_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, SABATES_COLORECTAL_ADENOMA_DN, GOBP_PROTEIN_LOCALIZATION_TO_SYNAPSE, DBP_Q6, PTF1BETA_Q6, GATA4_Q3, GOBP_LOCALIZATION_WITHIN_MEMBRANE, CUI_TCF21_TARGETS_2_UP

GO Biological Process (3): regulation of signal transduction (GO:0009966), cell migration (GO:0016477), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696)

GO Molecular Function (2): coreceptor activity (GO:0015026), protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), nucleus (GO:0005634), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), lysosomal lumen (GO:0043202), synapse (GO:0045202), side of membrane (GO:0098552), membrane (GO:0016020), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Dengue Virus Infection	2
Glycosaminoglycan metabolism	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
cell motility	1
regulation of biological quality	1
neurotransmitter receptor localization to postsynaptic specialization membrane	1
regulation of protein localization to synapse	1
regulation of receptor localization to synapse	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
signaling receptor activity	1
binding	1
intracellular membrane-bounded organelle	1
Golgi apparatus	1
intracellular organelle lumen	1
cell periphery	1
lysosome	1
vacuolar lumen	1
cell junction	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPC6	FZD2	Q14332	571
GPC6	NOTUM	Q6P988	562
GPC6	GPC5	P78333	559
GPC6	PTPRD	P23468	551
GPC6	SDC2	P34741	550
GPC6	GAPDH	P00354	493
GPC6	HS6ST3	Q8IZP7	477
GPC6	HSPG2	P98160	471
GPC6	MEGF10	Q96KG7	466
GPC6	GLCE	O94923	464
GPC6	SDC3	O75056	464
GPC6	SPARCL1	Q14515	464
GPC6	PCOLCE2	Q9UKZ9	449
GPC6	SDC4	P31431	449
GPC6	ENO1	P06733	439

IntAct

49 interactions, top by confidence:

A	B	Type	Score
GPC6	GPC4	psi-mi:“MI:0915”(physical association)	0.710
GPC6	GPC4	psi-mi:“MI:0914”(association)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
GPC4	SPCS2	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
APP	GPC6	psi-mi:“MI:0407”(direct interaction)	0.440
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
M2	AGPS	psi-mi:“MI:0914”(association)	0.350
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.350
MRPS7	ANKRD28	psi-mi:“MI:0914”(association)	0.350
DLX4	DIS3	psi-mi:“MI:0914”(association)	0.350
Gpr158	AGRN	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
SRP9	RPS3A	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS), GPC6 (Affinity Capture-MS)

ESM2 similar proteins: A2BDP1, A4IFM1, A4IHZ3, A5A6P7, B1AL88, F1QCC6, G3X745, L7VG99, O14525, O75487, O75949, O93279, P05067, P12023, P13265, P15943, P35052, P35053, P50593, P51653, P51654, P51655, P53601, P78333, P79307, P86009, Q06335, Q06481, Q0V9W0, Q14DG7, Q24114, Q32LT7, Q568B8, Q5EGE1, Q5IS80, Q5RE54, Q60495, Q61137, Q6P1U2, Q6V9Y8

Diamond homologs: F1QCC6, G3X745, O75487, P35052, P35053, P50593, P51653, P51655, Q0V9W0, Q5RE54, Q8BKV1, Q8N158, Q9QZF2, Q9R087, Q9Y625

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
NFATC2	“up-regulates quantity by expression”	GPC6	“transcriptional regulation”
NFATC1	“up-regulates quantity by expression”	GPC6	“transcriptional regulation”
NFATC4	“up-regulates quantity by expression”	GPC6	“transcriptional regulation”
NFATC3	“up-regulates quantity by expression”	GPC6	“transcriptional regulation”
GPC6	“up-regulates activity”	SHH	binding
GPC6	“down-regulates activity”	WNT5A	binding
GPC6	“up-regulates activity”	PTCH1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	0
Uncertain significance	203
Likely benign	84
Benign	62

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1072242	NC_000013.10:g.(?94482407)(94482798_?)del	Pathogenic
1076013	NM_005708.5(GPC6):c.433_451del (p.Glu145fs)	Pathogenic
1356390	NM_005708.5(GPC6):c.511C>T (p.Arg171Trp)	Pathogenic
2425402	NC_000013.10:g.(?93879710)(94482818_?)del	Pathogenic
5549	NM_005708.5(GPC6):c.778del (p.Leu260fs)	Pathogenic
5550	NC_000013.11:g.93997007_94063501del66495insATAAATCACTTAGAGATGT	Pathogenic
5551	NC_000013.11:g.94252984_94352299del99316insCTA	Pathogenic
5553	NM_005708.3(GPC6):c.712_877dup	Pathogenic
685089	GRCh37/hg19 13q31.3(chr13:94097218-94204671)x1	Pathogenic
687181	GRCh37/hg19 13q31.3(chr13:94120662-94430587)x1	Pathogenic

SpliceAI

4205 predictions. Top by Δscore:

Variant	Effect	Δscore
13:93545258:TGCA:T	acceptor_loss	1.0000
13:93545259:GCAG:G	acceptor_loss	1.0000
13:93545260:CAG:C	acceptor_loss	1.0000
13:93545261:A:AG	acceptor_gain	1.0000
13:93545261:A:G	acceptor_loss	1.0000
13:93545262:G:GA	acceptor_loss	1.0000
13:93545262:G:GG	acceptor_gain	1.0000
13:93545405:GCA:G	donor_gain	1.0000
13:93545418:GACG:G	donor_gain	1.0000
13:93545422:G:GA	donor_loss	1.0000
13:93545422:G:GG	donor_gain	1.0000
13:93545423:TAGG:T	donor_loss	1.0000
13:93227617:G:A	donor_loss	0.9900
13:93227618:T:G	donor_loss	0.9900
13:93545261:AG:A	acceptor_gain	0.9900
13:93545261:AGG:A	acceptor_gain	0.9900
13:93545261:AGGG:A	acceptor_gain	0.9900
13:93545262:GG:G	acceptor_gain	0.9900
13:93545262:GGG:G	acceptor_gain	0.9900
13:93545262:GGGG:G	acceptor_gain	0.9900
13:93545262:GGGGA:G	acceptor_gain	0.9900
13:93548359:A:G	acceptor_gain	0.9900
13:93570697:A:AG	acceptor_gain	0.9900
13:93570698:G:GG	acceptor_gain	0.9900
13:93625591:GA:G	donor_gain	0.9900
13:93757752:G:GT	donor_gain	0.9900
13:93227613:GCAG:G	donor_gain	0.9800
13:93227617:G:GG	donor_gain	0.9800
13:93279232:G:GA	donor_gain	0.9800
13:93587797:C:G	donor_gain	0.9800

AlphaMissense

3683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:93545280:T:A	C60S	1.000
13:93545280:T:C	C60R	1.000
13:93545281:G:C	C60S	1.000
13:93545301:T:A	C67S	1.000
13:93545301:T:C	C67R	1.000
13:93545302:G:C	C67S	1.000
13:93830169:T:C	L112P	1.000
13:93830180:G:C	A116P	1.000
13:93830193:T:C	L120P	1.000
13:93830204:T:C	F124L	1.000
13:93830205:T:C	F124S	1.000
13:93830205:T:G	F124C	1.000
13:93830206:T:A	F124L	1.000
13:93830206:T:G	F124L	1.000
13:93830220:G:T	G129V	1.000
13:93830228:T:G	Y132D	1.000
13:93830249:T:C	F139L	1.000
13:93830251:C:A	F139L	1.000
13:93830251:C:G	F139L	1.000
13:93830259:T:C	L142P	1.000
13:93830271:T:C	L146P	1.000
13:93830316:T:C	L161P	1.000
13:93830324:T:C	F164L	1.000
13:93830326:T:A	F164L	1.000
13:93830326:T:G	F164L	1.000
13:93830327:T:A	W165R	1.000
13:93830327:T:C	W165R	1.000
13:93830329:G:C	W165C	1.000
13:93830329:G:T	W165C	1.000
13:93830337:T:C	L168P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000186 (13:93735917 G>A,T), RS1000000624 (13:94101298 A>G,T), RS1000000744 (13:93805433 T>C), RS1000001506 (13:93469453 A>G), RS1000003598 (13:94144479 T>C), RS1000005003 (13:93848799 C>G,T), RS1000005158 (13:93289380 T>C), RS1000011461 (13:93499269 T>G), RS1000015000 (13:94357133 A>G), RS1000016620 (13:94049527 G>A), RS1000018928 (13:93362341 G>A,T), RS1000027510 (13:93224190 G>A,C,T), RS1000027621 (13:93354708 A>C), RS1000032008 (13:94404869 A>T), RS1000035410 (13:93540111 T>G)

Disease associations

OMIM: gene MIM:604404 | disease phenotypes: MIM:258315

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive omodysplasia	Strong	Autosomal recessive

Mondo (1): autosomal recessive omodysplasia (MONDO:0009779)

Orphanet (2): Omodysplasia (Orphanet:2733), Autosomal recessive omodysplasia (Orphanet:93329)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000581	Blepharophimosis
HP:0000944	Abnormal metaphysis morphology
HP:0001028	Hemangioma
HP:0001059	Pterygium
HP:0001060	Axillary pterygium
HP:0001249	Intellectual disability
HP:0001363	Craniosynostosis
HP:0001377	Limited elbow extension
HP:0001537	Umbilical hernia
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0002007	Frontal bossing
HP:0002818	Abnormal morphology of the radius
HP:0002823	Abnormal femur morphology
HP:0002983	Micromelia
HP:0003027	Mesomelia
HP:0003038	Fibular hypoplasia
HP:0003042	Elbow dislocation
HP:0003066	Limited knee extension

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000107_4	Tonometry	2.000000e-06
GCST000246_10	Attention deficit hyperactivity disorder	1.000000e-08
GCST000724_1	Neuroticism (age interaction)	1.000000e-07
GCST001304_6	Renal sinus fat	6.000000e-06
GCST001525_16	Visceral fat	4.000000e-06
GCST001585_35	Breast size	3.000000e-06
GCST001687_35	Disc degeneration (lumbar)	9.000000e-07
GCST001762_243	Obesity-related traits	4.000000e-07
GCST001762_587	Obesity-related traits	4.000000e-07
GCST001762_783	Obesity-related traits	7.000000e-07
GCST001915_31	Alzheimer’s disease (cognitive decline)	7.000000e-08
GCST002365_3	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 2 peripheral neuropathy)	2.000000e-07
GCST002587_22	Blood pressure (smoking interaction)	6.000000e-07
GCST002587_23	Blood pressure (smoking interaction)	2.000000e-06
GCST002782_16	Waist-to-hip ratio adjusted for body mass index	2.000000e-06
GCST002782_17	Waist-to-hip ratio adjusted for body mass index	8.000000e-06
GCST003226_18	Pelvic organ prolapse	6.000000e-06
GCST003542_155	Night sleep phenotypes	7.000000e-06
GCST004064_54	Waist-hip ratio	2.000000e-08
GCST006288_159	Heel bone mineral density	8.000000e-06
GCST006288_398	Heel bone mineral density	2.000000e-06
GCST006288_427	Heel bone mineral density	6.000000e-09
GCST006288_428	Heel bone mineral density	1.000000e-10
GCST006291_71	Spherical equivalent or myopia (age of diagnosis)	4.000000e-10
GCST006979_1031	Heel bone mineral density	8.000000e-16
GCST006979_1032	Heel bone mineral density	2.000000e-14
GCST006979_1033	Heel bone mineral density	8.000000e-35
GCST006979_1034	Heel bone mineral density	6.000000e-10
GCST006979_1035	Heel bone mineral density	2.000000e-22
GCST007396_1	Mitochondrial DNA copy number (white blood cells)	9.000000e-07

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0008007	age at assessment
EFO:0004864	renal sinus adipose tissue measurement
EFO:0005106	body composition measurement
EFO:0000180	HIV-1 infection
EFO:0006335	systolic blood pressure
EFO:0006525	cigarettes per day measurement
EFO:0006526	pack-years measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004343	waist-hip ratio
EFO:0009270	heel bone mineral density
EFO:0004847	age at onset
EFO:0006312	mitochondrial DNA measurement
EFO:0008328	chronotype measurement
EFO:0004517	arterial stiffness measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004810	interleukin-6 measurement
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	8
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
Arsenic	affects methylation, decreases expression, increases abundance, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects methylation, affects cotreatment, increases expression	2
sodium arsenite	increases abundance, increases expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
arsenite	decreases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
clothianidin	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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