DYM

Summary

DYM (dymeclin, HGNC:21317) is a protein-coding gene on chromosome 18q21.1, encoding Dymeclin (Q7RTS9). Necessary for correct organization of Golgi apparatus.

This gene encodes a protein which regulates Golgi-associated secretory pathways that are essential to endochondral bone formation during early development. This gene is also believed to play a role in early brain development. This gene is widely expressed in embryos and is particularly abundant in chodrocytes and brain tissues. It encodes a peripheral membrane protein which shuttles between the cytosol and Golgi complex. Mutations in this gene are associated with two types of recessive osteochondrodysplasia: Dyggve-Melchior-Clausen (DMC) dysplasia and Smith-McCort (SMC) dysplasia.

Source: NCBI Gene 54808 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Dyggve-Melchior-Clausen disease (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 78
• Clinical variants (ClinVar): 398 total — 32 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 118
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001353214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21317
Approved symbol	DYM
Name	dymeclin
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20071, DMC, SMC
Ensembl gene	ENSG00000141627
Ensembl biotype	protein_coding
OMIM	607461
Entrez	54808

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 18 protein_coding, 7 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000269445, ENST00000418472, ENST00000442713, ENST00000577481, ENST00000577734, ENST00000577836, ENST00000578396, ENST00000578596, ENST00000579058, ENST00000580615, ENST00000581409, ENST00000581738, ENST00000582095, ENST00000583225, ENST00000583270, ENST00000583280, ENST00000583353, ENST00000584977, ENST00000584983, ENST00000675505, ENST00000889574, ENST00000889575, ENST00000919567, ENST00000919568, ENST00000919569, ENST00000952642, ENST00000952643, ENST00000952644

RefSeq mRNA: 25 — MANE Select: NM_001353214 NM_001353210, NM_001353211, NM_001353212, NM_001353213, NM_001353214, NM_001353215, NM_001353216, NM_001374428, NM_001374429, NM_001374430, NM_001374431, NM_001374432, NM_001374433, NM_001374434, NM_001374435, NM_001374436, NM_001374437, NM_001374438, NM_001374439, NM_001374440, NM_001374441, NM_001374442, NM_001374443, NM_001374444, NM_017653

CCDS: CCDS11937, CCDS92459, CCDS92460

Canonical transcript exons

ENST00000675505 — 18 exons

Exon	Start	End
ENSE00001111116	49258380	49258493
ENSE00001240973	49257010	49257104
ENSE00001597732	49118744	49118926
ENSE00001612280	49281997	49282175
ENSE00001636108	49272178	49272303
ENSE00001644520	49209551	49209715
ENSE00001676233	49286434	49286616
ENSE00001696568	49097402	49097515
ENSE00002697479	49163685	49163787
ENSE00002703924	49460398	49460645
ENSE00003476761	49363161	49363233
ENSE00003481230	49391593	49391645
ENSE00003562337	49430255	49430447
ENSE00003612262	49333728	49333853
ENSE00003662652	49379665	49379758
ENSE00003678249	49378567	49378700
ENSE00003689819	49331864	49332006
ENSE00003902288	49036387	49044204

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 94.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.0216 / max 922.2382, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171907	47.5441	1820
171903	0.3656	149
171906	0.0940	19
171898	0.0099	3
171897	0.0080	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	94.52	gold quality
embryo	UBERON:0000922	93.84	gold quality
ganglionic eminence	UBERON:0004023	93.84	gold quality
body of pancreas	UBERON:0001150	93.82	gold quality
cortical plate	UBERON:0005343	93.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.52	gold quality
tibialis anterior	UBERON:0001385	93.33	gold quality
muscle of leg	UBERON:0001383	93.21	gold quality
right testis	UBERON:0004534	93.13	gold quality
gastrocnemius	UBERON:0001388	93.10	gold quality
left testis	UBERON:0004533	93.08	gold quality
pancreas	UBERON:0001264	92.42	gold quality
calcaneal tendon	UBERON:0003701	92.42	gold quality
skeletal muscle organ	UBERON:0014892	92.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.15	gold quality
deltoid	UBERON:0001476	92.06	gold quality
stromal cell of endometrium	CL:0002255	91.97	gold quality
cartilage tissue	UBERON:0002418	91.97	gold quality
smooth muscle tissue	UBERON:0001135	91.82	gold quality
colonic epithelium	UBERON:0000397	91.60	gold quality
testis	UBERON:0000473	91.32	gold quality
ventricular zone	UBERON:0003053	91.28	gold quality
sperm	CL:0000019	91.18	gold quality
leukocyte	CL:0000738	91.01	gold quality
islet of Langerhans	UBERON:0000006	90.97	gold quality
monocyte	CL:0000576	90.96	gold quality
adrenal tissue	UBERON:0018303	90.88	gold quality
sural nerve	UBERON:0015488	90.36	gold quality
skeletal muscle tissue	UBERON:0001134	89.80	gold quality
gall bladder	UBERON:0002110	89.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, ETV1, HEY2, KLF5, MYBL2, PITX2, TP53

miRNA regulators (miRDB)

21 targeting DYM, 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-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-934	98.49	70.44	581
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-5591-3P	96.23	67.03	489

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 9)

• Gene mutations in a novel, evolutionarily conserved gene are identified in both rare autosomal recessive osteochondrodysplasias (DMC and SMC). (PMID:12491225)
• Mutations cause Dyggve-Melchior-Clausen syndrome. Normal function may be in process of intracellular digestion of proteins. (PMID:12554689)
• DYM mutations associated with Dyggve-Melchior-Clausen dysplasia result in mis-localization of Dymeclin. (PMID:18996921)
• dymeclin gene has a role in Golgi function and vesicular transport in the presynapse in schizophrenia in the Japanese population (PMID:20555340)
• A novel homozygous splice-site mutation (IVS15+3G>T)of dymeclin gene in the 18q12-12.1 chromosomal region was detected in Dyggve-Melchior-Clausen syndrome. (PMID:20865280)
• Data reveal Dymeclin driven processes central to bone development pathways, including Golgi organization, Golgi-coupled protein secretion, and collagen deposition in the extracellular matrix. (PMID:21280149)
• The clinical diagnosis was confirmed with molecular analysis of DYM with a known mutation at c.580C>T (p.R194X). (PMID:24300288)
• Dymeclin is crucial for proper myelination and anterograde neuronal trafficking, two processes that are highly active during postnatal brain maturation. (PMID:25652408)
• A homozygous nonsense variant in DYM underlies Dyggve-Melchior-Clausen syndrome associated with ectodermal features. (PMID:32886330)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dym	ENSDARG00000042555
mus_musculus	Dym	ENSMUSG00000035765
rattus_norvegicus	Dym	ENSRNOG00000018425
drosophila_melanogaster	CG8230	FBGN0027607
caenorhabditis_elegans		WBGENE00008136

Protein

Protein identifiers

Dymeclin — Q7RTS9 (reviewed: Q7RTS9)

Alternative names: Dyggve-Melchior-Clausen syndrome protein

All UniProt accessions (11): A0A6Q8PF81, E9PG80, J3KRG4, J3KSF9, J3KTF2, J3QQT7, J3QR81, J3QRD8, J3QRF2, J3QSE7, Q7RTS9

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for correct organization of Golgi apparatus. Involved in bone development.

Subunit / interactions. Interacts with GOLM1 and PPIB.

Subcellular location. Cytoplasm. Golgi apparatus. Membrane.

Tissue specificity. Expressed in most embryo-fetal and adult tissues. Abundant in primary chondrocytes, osteoblasts, cerebellum, kidney, lung, stomach, heart, pancreas and fetal brain. Very low or no expression in the spleen, thymus, esophagus, bladder and thyroid gland.

Post-translational modifications. Myristoylated in vitro; myristoylation is not essential for protein targeting to Golgi compartment.

Disease relevance. Dyggve-Melchior-Clausen syndrome (DMC) [MIM:223800] A rare autosomal recessive disorder belonging to the group of spondyloepimetaphyseal dysplasias. DMC is characterized by progressive short stature with short trunk dwarfism, microcephaly, protruding sternum, and psychomotor retardation. Radiological features include a platyspondyly with double vertebral humps, an epiphyso-metaphyseal dysplasia and lacy pelvis iliac crests. The disease is caused by variants affecting the gene represented in this entry. Smith-McCort dysplasia 1 (SMC1) [MIM:607326] A rare autosomal recessive osteochondrodysplasia with skeletal features identical to those of Dyggve-Melchior-Clausen syndrome, but with normal intelligence and no microcephaly. It is characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the dymeclin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7RTS9-1	1	yes
Q7RTS9-2	2

RefSeq proteins (25): NP_001340139, NP_001340140, NP_001340141, NP_001340142, NP_001340143, NP_001340144, NP_001340145, NP_001361357, NP_001361358, NP_001361359, NP_001361360, NP_001361361, NP_001361362, NP_001361363, NP_001361364, NP_001361365, NP_001361366, NP_001361367, NP_001361368, NP_001361369, NP_001361370, NP_001361371, NP_001361372, NP_001361373, NP_060123 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019142	Dymeclin	Family

Pfam: PF09742

UniProt features (15 total): sequence conflict 6, sequence variant 3, splice variant 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTS9-F1	87.91	0.72

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): 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	does not affect protein localization to golgi apparatus. prevents myristoylation in vitro.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 357 (showing top): GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GGCNKCCATNK_UNKNOWN, GOBP_BONE_DEVELOPMENT, MYCMAX_01, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_GOLGI_ORGANIZATION, MYCMAX_03, MAX_01, ARNT_01, chr18q21, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, SNACANNNYSYAGA_UNKNOWN, PRC1_BMI_UP.V1_UP

GO Biological Process (2): Golgi organization (GO:0007030), bone development (GO:0060348)

GO Molecular Function (2): enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
organelle organization	1
endomembrane system organization	1
skeletal system development	1
animal organ development	1
protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYM	PAPSS2	O95340	930
DYM	CTIF	O43310	643
DYM	HID1	Q8IV36	597
DYM	RAB33B	Q9H082	507
DYM	SH3GL3	Q99963	479
DYM	VPS50	Q96JG6	461
DYM	UNC79	Q9P2D8	456
DYM	BTBD7	Q9P203	455
DYM	ITGB1BP2	Q9UKP3	453
DYM	XYLT1	Q86Y38	448
DYM	ZBTB38	Q8NAP3	429
DYM	HHIP	Q96QV1	429
DYM	CTDSP2	O14595	427
DYM	BCKDHB	P21953	427
DYM	PPP6R3	Q5H9R7	427

IntAct

101 interactions, top by confidence:

A	B	Type	Score
HS2ST1	SLC7A1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
DYM	PPIB	psi-mi:“MI:0915”(physical association)	0.600
DYM	PPIB	psi-mi:“MI:0403”(colocalization)	0.600
DYM	GOLM1	psi-mi:“MI:0915”(physical association)	0.580
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
SLCO1B3	LGALS3	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
GPR17	IPO8	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS), DYM (Affinity Capture-MS)

ESM2 similar proteins: A0JNG7, A0JPF5, A0JPG1, A2VE70, B0V207, B1AY13, B4F766, F1QFR9, F1R2X6, O17482, O43156, P49021, P50851, Q05DH4, Q0P4Q0, Q15021, Q4S6U8, Q505K2, Q5PNP1, Q5RAW5, Q5SP90, Q5SSW2, Q5W0V3, Q5ZLW3, Q6DCP6, Q6IN85, Q6INN7, Q6NRP2, Q6P2K6, Q7RTS9, Q80TR8, Q80YR2, Q86V87, Q8CDM8, Q8CHY3, Q8IV36, Q8IY22, Q8K2Z4, Q8NFP9, Q8R1F6

Diamond homologs: B0G194, B4F766, Q28BM0, Q293C2, Q5RAW5, Q5ZLW3, Q6DCP6, Q7KNA0, Q7RTS9, Q8CHY3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 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
Transport of vitamins, nucleosides, and related molecules	5	16.4×	5e-04
G alpha (q) signalling events	12	8.3×	5e-06
Class A/1 (Rhodopsin-like receptors)	9	8.0×	1e-04
GPCR ligand binding	9	7.0×	4e-04
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	6	6.3×	1e-02
Peptide ligand-binding receptors	7	6.2×	5e-03
G alpha (i) signalling events	11	5.2×	4e-04
Signaling by GPCR	9	4.3×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	6	18.4×	9e-05
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	8	15.9×	7e-06
phospholipase C-activating G protein-coupled receptor signaling pathway	11	13.2×	3e-07
positive regulation of cytosolic calcium ion concentration	10	10.6×	7e-06
calcium-mediated signaling	6	10.0×	2e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	9	9.2×	7e-05
chemotaxis	7	8.7×	2e-03
G protein-coupled receptor signaling pathway	20	6.6×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	15
Uncertain significance	157
Likely benign	118
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027549	NM_001353214.3(DYM):c.719C>A (p.Ser240Ter)	Pathogenic
1048086	NM_001353214.3(DYM):c.1650dup (p.His551fs)	Pathogenic
1048089	NM_001353214.3(DYM):c.1653_1654del (p.His551fs)	Pathogenic
1048091	NM_001353214.3(DYM):c.705_708dup (p.Pro237fs)	Pathogenic
1048092	NM_001353214.3(DYM):c.963del (p.Ser322fs)	Pathogenic
1069585	NM_001353214.3(DYM):c.673C>T (p.Gln225Ter)	Pathogenic
1076840	NM_001353214.3(DYM):c.368del (p.Glu123fs)	Pathogenic
1322791	NM_001353214.3(DYM):c.59T>A (p.Leu20Ter)	Pathogenic
1679898	NM_001353214.3(DYM):c.445dup (p.Glu149fs)	Pathogenic
1704249	NM_001353214.3(DYM):c.1177_1178del (p.His393fs)	Pathogenic
191091	NM_001353214.3(DYM):c.2025+1G>A	Pathogenic
195317	NM_001353214.3(DYM):c.122del (p.Phe41fs)	Pathogenic
1982956	NM_001353214.3(DYM):c.1678C>T (p.Gln560Ter)	Pathogenic
198883	NM_001353214.3(DYM):c.621-2A>G	Pathogenic
2035245	NM_001353214.3(DYM):c.1205T>A (p.Leu402Ter)	Pathogenic
2503430	NM_001353214.3(DYM):c.610C>T (p.Arg204Ter)	Pathogenic
265106	NM_001353214.3(DYM):c.1669C>T (p.Gln557Ter)	Pathogenic
3184	NM_001353214.3(DYM):c.48C>G (p.Tyr16Ter)	Pathogenic
3185	NM_001353214.3(DYM):c.763del (p.Thr255fs)	Pathogenic
3187	NM_001353214.3(DYM):c.1405A>T (p.Asn469Tyr)	Pathogenic
3189	NM_001353214.3(DYM):c.259G>A (p.Glu87Lys)	Pathogenic
3190	NM_001353214.3(DYM):c.1252-1G>A	Pathogenic
3192	NM_001353214.3(DYM):c.422-2A>G	Pathogenic
3193	NM_001353214.3(DYM):c.1789T>C (p.Cys597Arg)	Pathogenic
4277933	NM_001353214.3(DYM):c.836del (p.Pro279fs)	Pathogenic
4691707	NM_001353214.3(DYM):c.312_313dup (p.Asn105fs)	Pathogenic
4732562	NM_001353214.3(DYM):c.780dup (p.Phe261fs)	Pathogenic
4781688	NM_001353214.3(DYM):c.1152T>A (p.Tyr384Ter)	Pathogenic
813511	NM_001353214.3(DYM):c.95dup (p.Trp33fs)	Pathogenic
870744	NM_001353214.3(DYM):c.2103_2107del (p.Val702fs)	Pathogenic

SpliceAI

5379 predictions. Top by Δscore:

Variant	Effect	Δscore
18:49118736:ACACT:A	donor_loss	1.0000
18:49118737:CACTC:C	donor_loss	1.0000
18:49118738:ACTCA:A	donor_loss	1.0000
18:49118739:C:CG	donor_loss	1.0000
18:49118740:TCACC:T	donor_loss	1.0000
18:49118741:C:CC	donor_loss	1.0000
18:49118743:C:CA	donor_loss	1.0000
18:49118763:ATAT:A	donor_gain	1.0000
18:49118766:T:TA	donor_gain	1.0000
18:49118925:GCCT:G	acceptor_loss	1.0000
18:49118926:CCT:C	acceptor_gain	1.0000
18:49118927:C:CC	acceptor_gain	1.0000
18:49118927:C:T	acceptor_gain	1.0000
18:49118927:CTT:C	acceptor_loss	1.0000
18:49118928:T:C	acceptor_gain	1.0000
18:49118928:T:TC	acceptor_gain	1.0000
18:49118930:A:AC	acceptor_gain	1.0000
18:49118930:A:C	acceptor_gain	1.0000
18:49257005:TTTAC:T	donor_loss	1.0000
18:49257006:TTA:T	donor_loss	1.0000
18:49257007:TA:T	donor_loss	1.0000
18:49257008:ACCTG:A	donor_loss	1.0000
18:49257009:C:CA	donor_loss	1.0000
18:49257102:GTCC:G	acceptor_loss	1.0000
18:49257103:TCC:T	acceptor_loss	1.0000
18:49257105:C:CA	acceptor_loss	1.0000
18:49257105:C:CC	acceptor_gain	1.0000
18:49257117:A:T	acceptor_gain	1.0000
18:49258372:ATACT:A	donor_loss	1.0000
18:49258373:TACTT:T	donor_loss	1.0000

AlphaMissense

4733 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:49044151:A:C	F638L	1.000
18:49044151:A:T	F638L	1.000
18:49044153:A:G	F638L	1.000
18:49044179:T:C	Y629C	1.000
18:49044180:A:G	Y629H	1.000
18:49044184:G:C	F627L	1.000
18:49044184:G:T	F627L	1.000
18:49044185:A:G	F627S	1.000
18:49044186:A:G	F627L	1.000
18:49257058:G:C	S471W	1.000
18:49257063:A:C	N469K	1.000
18:49257063:A:T	N469K	1.000
18:49257068:C:G	A468P	1.000
18:49257073:G:T	A466D	1.000
18:49257076:G:T	A465E	1.000
18:49257084:A:C	N462K	1.000
18:49257084:A:T	N462K	1.000
18:49257094:A:G	L459P	1.000
18:49257097:T:C	Y458C	1.000
18:49257103:T:A	D456V	1.000
18:49257103:T:G	D456A	1.000
18:49257104:C:G	D456H	1.000
18:49258395:G:C	N450K	1.000
18:49258395:G:T	N450K	1.000
18:49258434:A:C	S437R	1.000
18:49258434:A:T	S437R	1.000
18:49258436:T:G	S437R	1.000
18:49258439:C:A	G436W	1.000
18:49258439:C:G	G436R	1.000
18:49258439:C:T	G436R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006829 (18:49459230 A>G), RS1000007935 (18:49446809 A>G), RS1000009090 (18:49417761 T>C), RS1000010835 (18:49330268 C>A,T), RS1000026051 (18:49041053 G>A), RS1000029197 (18:49119859 G>A,C), RS1000034456 (18:49374709 A>G), RS1000042151 (18:49323207 C>CA), RS1000044308 (18:49156508 G>C), RS1000048435 (18:49379446 A>G), RS1000049716 (18:49285597 C>G,T), RS1000055 (18:49054943 G>A), RS1000057872 (18:49415345 A>T), RS1000057899 (18:49047639 C>A,T), RS1000058327 (18:49199310 T>C)

Disease associations

OMIM: gene MIM:607461 | disease phenotypes: MIM:223800, MIM:181500, MIM:607326, MIM:601371

GenCC curated gene-disease

Disease	Classification	Inheritance
Dyggve-Melchior-Clausen disease	Definitive	Autosomal recessive
Smith-McCort dysplasia 1	Strong	Autosomal recessive
Smith-McCort dysplasia	Supportive	Autosomal recessive

Mondo (7): Dyggve-Melchior-Clausen disease (MONDO:0009130), prostate cancer (MONDO:0008315), connective tissue disorder (MONDO:0003900), schizophrenia (MONDO:0005090), Smith-McCort dysplasia 1 (MONDO:0011814), early-onset non-syndromic cataract (MONDO:0011060), Smith-McCort dysplasia (MONDO:0015799)

Orphanet (4): Dyggve-Melchior-Clausen disease (Orphanet:239), Familial prostate cancer (Orphanet:1331), Early onset non-syndromic cataract (Orphanet:91492), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000280	Coarse facial features
HP:0000303	Mandibular prognathia
HP:0000319	Smooth philtrum
HP:0000365	Hearing impairment
HP:0000470	Short neck
HP:0000574	Thick eyebrow
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000768	Pectus carinatum
HP:0000882	Hypoplastic scapulae
HP:0000884	Prominent sternum
HP:0000885	Broad ribs
HP:0000911	Flat glenoid fossa
HP:0000914	Shield chest
HP:0000920	Enlargement of the costochondral junction
HP:0000925	Abnormality of the vertebral column
HP:0000926	Platyspondyly
HP:0000946	Hypoplastic ilia
HP:0001156	Brachydactyly
HP:0001169	Broad palm
HP:0001249	Intellectual disability
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001285	Spastic tetraparesis
HP:0001288	Gait disturbance

GWAS associations

78 associations (top):

Study	Trait	p-value
GCST000174_14	Height	3.000000e-07
GCST000817_125	Height	9.000000e-25
GCST001263_32	Height	1.000000e-10
GCST001290_8	Height	7.000000e-10
GCST001956_42	Height	5.000000e-09
GCST002702_105	Height	5.000000e-16
GCST004067_173	Hip circumference adjusted for BMI	3.000000e-07
GCST004067_187	Hip circumference adjusted for BMI	3.000000e-10
GCST004067_71	Hip circumference adjusted for BMI	9.000000e-15
GCST004210_6	Body fat percentage	3.000000e-08
GCST006186_2	Systolic blood pressure x smoking status (current vs non-current) interaction (1df test)	8.000000e-06
GCST006195_92	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-08
GCST007294_20	Body fat distribution (trunk fat ratio)	5.000000e-10
GCST007294_39	Body fat distribution (trunk fat ratio)	2.000000e-10
GCST007295_167	Body fat distribution (leg fat ratio)	4.000000e-08
GCST007295_2	Body fat distribution (leg fat ratio)	5.000000e-07
GCST008163_158	Height	6.000000e-08
GCST008163_347	Height	3.000000e-08
GCST008163_541	Height	3.000000e-10
GCST008163_619	Height	9.000000e-06
GCST008282_7	Spine bone size	1.000000e-12
GCST008839_346	Height	1.000000e-19
GCST010002_139	Refractive error	4.000000e-60
GCST010241_83	Apolipoprotein A1 levels	3.000000e-13
GCST010242_153	HDL cholesterol levels	6.000000e-12
GCST010866_159	Coronary artery disease	1.000000e-12
GCST011365_5	Myocardial infarction	2.000000e-08
GCST011739_9	Cutaneous leishmaniasis	2.000000e-06
GCST012227_714	Hip circumference adjusted for BMI	3.000000e-09
GCST012227_715	Hip circumference adjusted for BMI	4.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0007800	body fat percentage
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004341	body fat distribution
EFO:0004508	spine bone size
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0006941	grip strength measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C564589	Smith-McCort Dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	6
Cyclosporine	increases expression	3
Aflatoxin B1	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	increases expression	1
K 7174	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	increases abundance, affects expression	1
Selenium	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_5Q85	GM18308	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer