PCDH12

Summary

PCDH12 (protocadherin 12, HGNC:8657) is a protein-coding gene on chromosome 5q31.3, encoding Protocadherin-12 (Q9NPG4). Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions.

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth.

Source: NCBI Gene 51294 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diencephalic-mesencephalic junction dysplasia syndrome 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 489 total — 13 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_016580

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8657
Approved symbol	PCDH12
Name	protocadherin 12
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113555
Ensembl biotype	protein_coding
OMIM	605622
Entrez	51294

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000231484, ENST00000510041, ENST00000512221

RefSeq mRNA: 1 — MANE Select: NM_016580 NM_016580

CCDS: CCDS4269

Canonical transcript exons

ENST00000231484 — 4 exons

Exon	Start	End
ENSE00000766675	141951493	141951590
ENSE00000766676	141949432	141949583
ENSE00000814319	141954972	141958202
ENSE00001228238	141943581	141945805

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.13.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3064 / max 93.0428, expressed in 285 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63877	1.2042	283
63875	0.0650	40
63876	0.0372	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.13	gold quality
type B pancreatic cell	CL:0000169	89.49	gold quality
olfactory bulb	UBERON:0002264	89.22	silver quality
diaphragm	UBERON:0001103	87.37	gold quality
cervix squamous epithelium	UBERON:0006922	87.20	gold quality
placenta	UBERON:0001987	87.19	gold quality
right lung	UBERON:0002167	86.54	gold quality
apex of heart	UBERON:0002098	85.28	gold quality
vena cava	UBERON:0004087	85.18	silver quality
spleen	UBERON:0002106	84.14	gold quality
lung	UBERON:0002048	83.68	gold quality
upper lobe of lung	UBERON:0008948	82.27	gold quality
upper lobe of left lung	UBERON:0008952	82.16	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.04	silver quality
cardia of stomach	UBERON:0001162	81.51	silver quality
synovial joint	UBERON:0002217	81.49	gold quality
decidua	UBERON:0002450	81.44	silver quality
lower lobe of lung	UBERON:0008949	81.29	gold quality
substantia nigra pars compacta	UBERON:0001965	80.96	silver quality
lateral globus pallidus	UBERON:0002476	80.75	silver quality
saphenous vein	UBERON:0007318	80.68	silver quality
renal medulla	UBERON:0000362	80.65	silver quality
cervix epithelium	UBERON:0004801	80.60	gold quality
cerebellar vermis	UBERON:0004720	80.52	gold quality
body of tongue	UBERON:0011876	80.41	gold quality
inferior vagus X ganglion	UBERON:0005363	80.39	silver quality
visceral pleura	UBERON:0002401	80.27	gold quality
pericardium	UBERON:0002407	80.07	silver quality
layer of synovial tissue	UBERON:0007616	79.91	silver quality
heart left ventricle	UBERON:0002084	79.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting PCDH12, 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-4425	100.00	67.59	1049
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3922-3P	99.25	64.96	1136

Literature-anchored findings (GeneRIF, showing 10)

• A putative association was also found between protocadherin 12 and cortical folding (asymmetry coefficient of gyrification index). (PMID:19054571)
• PCDH12 may play an important role in human placental development, and proteolytic cleavage in response to external factors, such as cytokines and pathological settings, regulates its activity (PMID:21402705)
• Genome-wide analysis to determine the genetic cause of a microcephaly syndrome; found that loss of function of PCDH12 leads to recessive congenital microcephaly with profound developmental disability (PMID:27164683)
• WHSC1 gene variant is associated with dyskinetic cerebral palsy with epilepsy. (PMID:29904113)
• Autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia syndrome patients have biallelic mutations in PCDH12 and lack of protein expression. (PMID:30178464)
• Homozygous PCDH12 mutation is associated with cerebellar ataxia, dystonia, retinopathy, and dysmorphism. (PMID:30459466)
• Ophthalmic phenotypes associated with biallelic loss-of-function PCDH12 variants. (PMID:33527719)
• The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature. (PMID:34773825)
• PCDH12 variants are associated with basal ganglia anomalies and exudative vitreoretinopathy. (PMID:34929393)
• Asynchronous presentation and evolution of homozygous PCDH12 variant-induced exudative retinopathy in two siblings. (PMID:37536661)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcdh12	ENSDARG00000076594
mus_musculus	Pcdh12	ENSMUSG00000024440
rattus_norvegicus	Pcdh12	ENSRNOG00000019265

Paralogs (61): PCDHB4 (ENSG00000081818), PCDHA6 (ENSG00000081842), PCDHGA2 (ENSG00000081853), PCDHB2 (ENSG00000112852), PCDHB3 (ENSG00000113205), PCDHB5 (ENSG00000113209), PCDHB6 (ENSG00000113211), PCDHB7 (ENSG00000113212), PCDHB15 (ENSG00000113248), PCDH17 (ENSG00000118946), PCDHB8 (ENSG00000120322), PCDHB10 (ENSG00000120324), PCDHB14 (ENSG00000120327), PCDHB12 (ENSG00000120328), PCDH8 (ENSG00000136099), PCDH10 (ENSG00000138650), PCDH15 (ENSG00000150275), PCDH19 (ENSG00000165194), CDH16 (ENSG00000166589), PCDHB1 (ENSG00000171815), PCDHB9 (ENSG00000177839), PCDHB13 (ENSG00000187372), CDHR4 (ENSG00000187492), PCDH18 (ENSG00000189184), PCDHB11 (ENSG00000197479), PCDHGA1 (ENSG00000204956), PCDHA9 (ENSG00000204961), PCDHA8 (ENSG00000204962), PCDHA7 (ENSG00000204963), PCDHA5 (ENSG00000204965), PCDHA4 (ENSG00000204967), PCDHA2 (ENSG00000204969), PCDHA1 (ENSG00000204970), PCDHA13 (ENSG00000239389), PCDHGC3 (ENSG00000240184), PCDHGC5 (ENSG00000240764), PCDHGC4 (ENSG00000242419), PCDHAC2 (ENSG00000243232), PCDHAC1 (ENSG00000248383), PCDHA11 (ENSG00000249158)

Protein

Protein identifiers

Protocadherin-12 — Q9NPG4 (reviewed: Q9NPG4)

Alternative names: Vascular cadherin-2, Vascular endothelial cadherin-2

All UniProt accessions (2): Q9NPG4, E5RJD4

UniProt curated annotations — full annotation on UniProt →

Function. Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions. Acts as a regulator of cell migration, probably via increasing cell-cell adhesion. Promotes homotypic calcium-dependent aggregation and adhesion and clusters at intercellular junctions. Unable to bind to catenins, weakly associates with the cytoskeleton.

Subcellular location. Cell membrane. Cell junction Secreted.

Tissue specificity. Expressed in highly vascularized tissues including the heart and placenta, but most tissues contain a low level of expression. Prominent expression in the spleen. Present in villous and extravillous trophoblast (at protein level).

Post-translational modifications. Cleaved by ADAM10 close to the transmembrane domain to release the Protocadherin-12, secreted form in the serum. Cleavage results in reduced cellular adhesion in a cell migration assay.

Disease relevance. Diencephalic-mesencephalic junction dysplasia syndrome 1 (DMJDS1) [MIM:251280] An autosomal recessive syndrome characterized by severe global developmental delay with profound intellectual disability, spasticity or dystonia, and congenital microcephaly. Brain imaging shows hypothalamic midbrain dysplasia, diencephalic-mesencephalic dysplasia, and intracerebral calcifications. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_057664* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR013164	Cadherin_N	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR050174	Protocadherin/Cadherin-CA	Family

Pfam: PF00028, PF08266

UniProt features (38 total): sequence conflict 8, sequence variant 7, domain 6, glycosylation site 4, region of interest 3, chain 2, compositionally biased region 2, modified residue 2, topological domain 2, signal peptide 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPG4-F1	66.22	0.36

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 (2): 859, 1062

Glycosylation sites (4): 415, 582, 659, 662

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): CREL_01, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_NEURON_RECOGNITION, GCANCTGNY_MYOD_Q6, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, AP4_Q6, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT

GO Biological Process (6): glycogen metabolic process (GO:0005977), homophilic cell-cell adhesion (GO:0007156), neuron recognition (GO:0008038), calcium-dependent cell-cell adhesion (GO:0016339), labyrinthine layer development (GO:0060711), cell adhesion (GO:0007155)

GO Molecular Function (2): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (6): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
cellular anatomical structure	2
energy reserve metabolic process	1
glucan metabolic process	1
cell recognition	1
neuron development	1
embryonic placenta development	1
anatomical structure development	1
cellular process	1
metal ion binding	1
protein binding	1
membrane	1
cell periphery	1
anchoring junction	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCDH12	GCM1	Q9NP62	497
PCDH12	PHLDA2	Q53GA4	466
PCDH12	PCDH7	O60245	463
PCDH12	PCDH15	Q96QU1	447
PCDH12	GBE1	Q04446	438
PCDH12	GJB3	O75712	402
PCDH12	ASCL2	Q99929	399
PCDH12	PCDHGA1	Q9Y5H4	395
PCDH12	CDH5	P33151	379
PCDH12	PCDHGA10	Q9Y5H3	365
PCDH12	KIAA0319	Q5VV43	354
PCDH12	USHBP1	Q8N6Y0	306
PCDH12	NCAPD2	Q15021	293
PCDH12	VWF	P04275	280
PCDH12	NCAPD3	P42695	272

IntAct

8 interactions, top by confidence:

A	B	Type	Score
“BALF4	PCDH12	psi-mi:“MI:0915”(physical association)	0.370
FCGR1A	PCDH17	psi-mi:“MI:0914”(association)	0.350
PCDH12	PCDH17	psi-mi:“MI:0914”(association)	0.350
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
PCDH12	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): PCDH10 (Affinity Capture-MS), PCDH17 (Affinity Capture-MS), CLIC3 (Affinity Capture-MS), PCDHGA11 (Affinity Capture-MS), DCBLD1 (Affinity Capture-MS), CDON (Affinity Capture-MS), PTPRS (Affinity Capture-MS), PCDHGC3 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), ALCAM (Affinity Capture-MS), PCDH12 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), RPL23 (Affinity Capture-MS), EFNB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, D3YX43, O08644, O15197, O55134, O70394, O70540, O75309, O88338, P0C091, P0C0K6, P0C0K7, P0DP72, P21709, P40223, P59862, P70289, Q00657, Q04912, Q0V8J4, Q28634, Q501P1, Q53RD9, Q58Y75, Q5DRE2, Q5H8B9, Q5R6F5, Q5SZK8, Q60750, Q63315, Q64612, Q6MG64, Q6NVD0, Q6PFX6, Q6UVK1, Q76MJ5, Q7TN88, Q7Z442, Q86UP0

Diamond homologs: A6H8M9, O55134, O88338, P34616, Q5DRA2, Q5DRC0, Q5DRC3, Q5DRC4, Q5DRF3, Q91Y13, Q9NPG4, Q9Y5F6, Q9Y5H2, Q9Y5I1, A7MB46, D3ZE55, F8W3X3, O14917, O60330, O88689, O95206, Q5DRA3, Q5DRA4, Q5DRA5, Q5DRA6, Q5DRA7, Q5DRA8, Q5DRA9, Q5DRB0, Q5DRB1, Q5DRB2, Q5DRB3, Q5DRB4, Q5DRB5, Q5DRB6, Q5DRB7, Q5DRB8, Q5DRB9, Q5DRC1, Q5DRC2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	12
Uncertain significance	253
Likely benign	137
Benign	37

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1065612	NM_016580.4(PCDH12):c.2433C>A (p.Cys811Ter)	Pathogenic
1323420	NM_016580.4(PCDH12):c.2563C>T (p.Gln855Ter)	Pathogenic
1342872	NM_016580.4(PCDH12):c.451C>T (p.Arg151Ter)	Pathogenic
1711614	NM_016580.4(PCDH12):c.2424G>A (p.Trp808Ter)	Pathogenic
1905450	NM_016580.4(PCDH12):c.3009_3019del (p.Ser1003fs)	Pathogenic
2071056	NM_016580.4(PCDH12):c.418C>T (p.Gln140Ter)	Pathogenic
2124338	NM_016580.4(PCDH12):c.191_192dup (p.Ala65fs)	Pathogenic
4282439	NM_016580.4(PCDH12):c.2062C>T (p.Arg688Ter)	Pathogenic
440889	NM_016580.4(PCDH12):c.2515C>T (p.Arg839Ter)	Pathogenic
640849	NM_016580.4(PCDH12):c.2299C>T (p.Gln767Ter)	Pathogenic
684718	NM_016580.4(PCDH12):c.2511del (p.Ser838fs)	Pathogenic
684720	NM_016580.4(PCDH12):c.1060del (p.Val354fs)	Pathogenic
694061	PCDH12, ARG151TER	Pathogenic
1030562	NM_016580.4(PCDH12):c.115G>T (p.Glu39Ter)	Likely pathogenic
1343191	NM_016580.4(PCDH12):c.643A>C (p.Thr215Pro)	Likely pathogenic
1679306	NM_016580.4(PCDH12):c.207dup (p.Gln70fs)	Likely pathogenic
1804020	NM_016580.4(PCDH12):c.311G>A (p.Cys104Tyr)	Likely pathogenic
2426310	NC_000005.9:g.(?141333097)(141335037_?)del	Likely pathogenic
2443508	NM_016580.4(PCDH12):c.1235T>C (p.Leu412Ser)	Likely pathogenic
3256111	NM_016580.4(PCDH12):c.2675del (p.Gly892fs)	Likely pathogenic
3382378	NM_016580.4(PCDH12):c.2581G>T (p.Glu861Ter)	Likely pathogenic
3780103	NM_016580.4(PCDH12):c.2072del (p.Leu690_Leu691insTer)	Likely pathogenic
4075118	NM_016580.4(PCDH12):c.2169_2181del (p.Val724fs)	Likely pathogenic
4277803	NM_016580.4(PCDH12):c.39dup (p.Pro14fs)	Likely pathogenic
619128	NM_016580.4(PCDH12):c.2008G>T (p.Glu670Ter)	Likely pathogenic

SpliceAI

582 predictions. Top by Δscore:

Variant	Effect	Δscore
5:141949426:CCCTA:C	donor_loss	1.0000
5:141949427:CCTA:C	donor_loss	1.0000
5:141949428:CTAC:C	donor_loss	1.0000
5:141949429:TACCT:T	donor_loss	1.0000
5:141949430:A:C	donor_loss	1.0000
5:141949431:C:CA	donor_loss	1.0000
5:141949584:CT:C	acceptor_loss	1.0000
5:141945802:AGAC:A	acceptor_gain	0.9900
5:141945802:AGACC:A	acceptor_loss	0.9900
5:141945803:GAC:G	acceptor_gain	0.9900
5:141945803:GACCT:G	acceptor_loss	0.9900
5:141945804:ACCT:A	acceptor_loss	0.9900
5:141945806:C:A	acceptor_loss	0.9900
5:141945806:C:CC	acceptor_gain	0.9900
5:141945807:T:A	acceptor_loss	0.9900
5:141949430:A:AC	donor_gain	0.9900
5:141949431:C:CC	donor_gain	0.9900
5:141949579:CACTC:C	acceptor_gain	0.9900
5:141949580:ACTC:A	acceptor_gain	0.9900
5:141949581:CTC:C	acceptor_gain	0.9900
5:141949581:CTCC:C	acceptor_gain	0.9900
5:141949582:TC:T	acceptor_gain	0.9900
5:141949582:TCCT:T	acceptor_gain	0.9900
5:141949583:CC:C	acceptor_gain	0.9900
5:141949584:C:CC	acceptor_gain	0.9900
5:141949585:T:C	acceptor_loss	0.9900
5:141951587:TTTG:T	acceptor_gain	0.9900
5:141951591:C:CC	acceptor_gain	0.9900
5:141945801:CAGAC:C	acceptor_gain	0.9800
5:141945804:AC:A	acceptor_gain	0.9800

AlphaMissense

7708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:141957136:T:G	D239A	0.997
5:141957265:A:G	L196P	0.997
5:141957138:A:C	N238K	0.996
5:141957138:A:T	N238K	0.996
5:141957151:A:T	V234D	0.996
5:141957205:G:T	A216D	0.996
5:141957313:A:G	F180S	0.996
5:141956617:A:G	L412S	0.995
5:141956887:A:T	V322D	0.995
5:141957136:T:A	D239V	0.995
5:141957145:T:A	D236V	0.995
5:141957265:A:T	L196H	0.995
5:141951577:A:G	L965P	0.994
5:141956882:C:G	A324P	0.994
5:141957049:G:T	A268D	0.994
5:141957127:G:T	P242H	0.994
5:141957157:A:T	V232D	0.994
5:141956653:A:G	F400S	0.993
5:141956947:C:T	G302D	0.993
5:141957137:C:G	D239H	0.993
5:141957163:A:T	V230D	0.993
5:141957448:A:C	F135C	0.993
5:141957448:A:G	F135S	0.993
5:141956876:C:G	D326H	0.992
5:141956968:A:G	F295S	0.992
5:141957120:A:C	F244L	0.992
5:141957120:A:T	F244L	0.992
5:141957122:A:G	F244L	0.992
5:141957139:T:A	N238I	0.992
5:141957144:G:C	D236E	0.992

dbSNP variants (sampled 300 via entrez): RS1000035838 (5:141958479 C>T), RS1000041136 (5:141943922 C>G), RS1000195098 (5:141950448 T>A), RS1000242762 (5:141950696 G>A), RS1000398313 (5:141944653 T>G), RS1000687271 (5:141955494 A>C,G), RS1001366031 (5:141949316 T>A), RS1001579923 (5:141945032 CT>C), RS1002030722 (5:141945209 G>A), RS1002075575 (5:141950921 T>C), RS1002433432 (5:141958047 C>A,T), RS1002987870 (5:141947986 C>A,T), RS1003385798 (5:141946369 G>A), RS1003390432 (5:141946085 T>G), RS1003393018 (5:141959134 C>T)

Disease associations

OMIM: gene MIM:605622 | disease phenotypes: MIM:251280, MIM:154780, MIM:300216

GenCC curated gene-disease

Disease	Classification	Inheritance
diencephalic-mesencephalic junction dysplasia syndrome 1	Definitive	Autosomal recessive
diencephalic-mesencephalic junction dysplasia	Supportive	Autosomal recessive

Mondo (8): diencephalic-mesencephalic junction dysplasia syndrome 1 (MONDO:0009625), diencephalic-mesencephalic junction dysplasia (MONDO:0017868), Marshall syndrome (MONDO:0007949), neurodevelopmental disorder (MONDO:0700092), disorder of development or morphogenesis (MONDO:0021147), cerebellar ataxia (MONDO:0000437), dystonic disorder (MONDO:0003441), Coats disease (MONDO:0010269)

Orphanet (4): Diencephalic-mesencephalic junction dysplasia (Orphanet:319192), Marshall syndrome (Orphanet:560), Rare ataxia (Orphanet:102002), Coats disease (Orphanet:190)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000253	Progressive microcephaly
HP:0000505	Visual impairment
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001511	Intrauterine growth retardation
HP:0001622	Premature birth
HP:0002123	Generalized myoclonic seizure
HP:0002187	Profound intellectual disability
HP:0002266	Focal clonic seizure
HP:0002510	Spastic tetraplegia
HP:0002521	Hypsarrhythmia
HP:0003593	Infantile onset
HP:0008936	Axial hypotonia
HP:0011451	Primary microcephaly
HP:0012469	Infantile spasms
HP:0030674	Antenatal onset
HP:0032792	Tonic seizure

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005023_32	Initial pursuit acceleration	2.000000e-10
GCST005026_12	Initial pursuit acceleration in psychotic disorders	8.000000e-12
GCST009798_63	Asthma	9.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008434	initial pursuit acceleration

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D020821	Dystonic Disorders	C10.228.662.300
D065886	Neurodevelopmental Disorders	F03.625
D058456	Retinal Telangiectasis	C11.768.748; C14.907.823.502
C536025	Marshall syndrome (supp.)
C537546	Microcephaly with spastic quadriplegia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases expression	2
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Nickel	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children