PTCHD1

Summary

PTCHD1 (patched domain containing 1, HGNC:26392) is a protein-coding gene on chromosome Xp22.11, encoding Patched domain-containing protein 1 (Q96NR3). Required for the development and function of the thalamic reticular nucleus (TRN), a part of the thalamus that is critical for thalamocortical transmission, generation of sleep rhythms, sensorimotor processing and attention. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a membrane protein with a patched domain. The encoded protein is similar to Drosophila proteins which act as receptors for the morphogen sonic hedgehog. Deletions in this gene, which is located on the X chromosome, are associated with intellectual disability and autism (PMID: 21091464, PMID: 20844286).

Source: NCBI Gene 139411 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 373 total — 14 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 10
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_173495

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26392
Approved symbol	PTCHD1
Name	patched domain containing 1
Location	Xp22.11
Locus type	gene with protein product
Status	Approved
Aliases	SLC65C1, FLJ30296
Ensembl gene	ENSG00000165186
Ensembl biotype	protein_coding
OMIM	300828
Entrez	139411

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000379361, ENST00000456522, ENST00000903588

RefSeq mRNA: 1 — MANE Select: NM_173495 NM_173495

CCDS: CCDS35215

Canonical transcript exons

ENST00000379361 — 3 exons

Exon	Start	End
ENSE00001091060	23392531	23404374
ENSE00001091065	23379591	23380251
ENSE00001480653	23334849	23335226

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 90.59.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0942 / max 100.1364, expressed in 284 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195758	0.5882	251
195760	0.2835	87
195756	0.1636	75
195757	0.0589	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	90.59	gold quality
corpus epididymis	UBERON:0004359	90.09	gold quality
buccal mucosa cell	CL:0002336	86.43	silver quality
cerebellar vermis	UBERON:0004720	83.64	silver quality
cerebellum	UBERON:0002037	81.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.89	gold quality
cerebellar cortex	UBERON:0002129	80.39	gold quality
saphenous vein	UBERON:0007318	80.32	gold quality
cerebellar hemisphere	UBERON:0002245	80.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.67	gold quality
middle temporal gyrus	UBERON:0002771	78.52	gold quality
entorhinal cortex	UBERON:0002728	77.94	gold quality
pons	UBERON:0000988	77.77	gold quality
mucosa of stomach	UBERON:0001199	77.50	gold quality
substantia nigra pars compacta	UBERON:0001965	76.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.41	gold quality
lateral globus pallidus	UBERON:0002476	75.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.49	gold quality
postcentral gyrus	UBERON:0002581	74.25	gold quality
superior frontal gyrus	UBERON:0002661	73.90	gold quality
seminal vesicle	UBERON:0000998	73.70	gold quality
popliteal artery	UBERON:0002250	73.14	gold quality
tibial artery	UBERON:0007610	73.12	gold quality
superior vestibular nucleus	UBERON:0007227	73.07	gold quality
parietal lobe	UBERON:0001872	72.77	gold quality
ventral tegmental area	UBERON:0002691	70.77	gold quality
substantia nigra pars reticulata	UBERON:0001966	70.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.99	gold quality
globus pallidus	UBERON:0001875	69.70	silver quality
medial globus pallidus	UBERON:0002477	69.70	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting PTCHD1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6764-5P	99.75	67.89	2304

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• Systematic screen of PTCHD1 and its 5’ flanking regions suggests that this locus is involved in ~1% of individuals with autism spectrum disorder and intellectual disability. (PMID:20844286)
• Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism. (PMID:21091464)
• Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. (PMID:25131214)
• both common and rare PTCHD1 variants contribute to autism spectrum disorder. (PMID:25782667)
• Synaptic Dysfunction in Human Neurons With Autism-Associated Deletions in PTCHD1-AS. (PMID:31540669)
• Novel missense mutations in PTCHD1 alter its plasma membrane subcellular localization and cause intellectual disability and autism spectrum disorder. (PMID:33856728)
• CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction. (PMID:38007613)
• Nonsynonymous Mutations in Intellectual Disability and Autism Spectrum Disorder Gene PTCHD1 Disrupt N-Glycosylation and Reduce Protein Stability. (PMID:38275824)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptchd1	ENSDARG00000018066
mus_musculus	Ptchd1	ENSMUSG00000041552
rattus_norvegicus	Ptchd1	ENSRNOG00000069252
drosophila_melanogaster	ptc	FBGN0003892
drosophila_melanogaster	disp	FBGN0029088
drosophila_melanogaster	Ptr	FBGN0262867
caenorhabditis_elegans		WBGENE00004208
caenorhabditis_elegans		WBGENE00004211
caenorhabditis_elegans	ptr-17	WBGENE00004231

Paralogs (10): NPC1L1 (ENSG00000015520), SCAP (ENSG00000114650), PTCH2 (ENSG00000117425), DISP2 (ENSG00000140323), NPC1 (ENSG00000141458), DISP1 (ENSG00000154309), PTCHD3 (ENSG00000182077), PTCH1 (ENSG00000185920), DISP3 (ENSG00000204624), PTCHD4 (ENSG00000244694)

Protein

Protein identifiers

Patched domain-containing protein 1 — Q96NR3 (reviewed: Q96NR3)

All UniProt accessions (3): Q96NR3, H7C2M0, X5DNX9

UniProt curated annotations — full annotation on UniProt →

Function. Required for the development and function of the thalamic reticular nucleus (TRN), a part of the thalamus that is critical for thalamocortical transmission, generation of sleep rhythms, sensorimotor processing and attention. Can bind cholesterol in vitro.

Subcellular location. Cell membrane. Cell projection. Dendritic spine.

Tissue specificity. Widely expressed, including in various regions of the brain with highest expression in the gray and white cerebellum, followed by the cerebellar vermis and the pituitary gland.

Disease relevance. Autism, X-linked 4 (AUTSX4) [MIM:300830] A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the patched family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96NR3-1	1	yes
Q96NR3-2	2
Q96NR3-3	3

RefSeq proteins (1): NP_775766* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000731	SSD	Domain
IPR003392	PTHD_SSD	Domain
IPR051697	Patched_domain-protein	Family

Pfam: PF02460

UniProt features (49 total): sequence variant 19, transmembrane region 11, glycosylation site 10, sequence conflict 4, splice variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NR3-F1	84.14	0.43

Functional residue map

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

Glycosylation sites (10): 77, 133, 167, 319, 326, 568, 599, 608, 762, 818

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, FREAC2_01, GOBP_COGNITION, GOBP_BEHAVIOR, GCANCTGNY_MYOD_Q6, AREB6_01, FOXO4_01, AP2_Q3, FOXO1_01, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, SREBP1_02, GOBP_CELL_CELL_SIGNALING

GO Biological Process (11): smoothened signaling pathway (GO:0007224), chemical synaptic transmission (GO:0007268), short-term memory (GO:0007614), long-term memory (GO:0007616), thalamus development (GO:0021794), social behavior (GO:0035176), cognition (GO:0050890), excitatory chemical synaptic transmission (GO:0098976), inhibitory chemical synaptic transmission (GO:0098977), cell communication (GO:0007154), signaling (GO:0023052)

GO Molecular Function (0):

GO Cellular Component (5): plasma membrane (GO:0005886), dendritic spine (GO:0043197), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
memory	2
chemical synaptic transmission	2
cellular anatomical structure	2
cell surface receptor signaling pathway	1
anterograde trans-synaptic signaling	1
diencephalon development	1
anatomical structure development	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
nervous system process	1
excitatory postsynaptic potential	1
inhibitory postsynaptic potential	1
cellular process	1
regulation of biological process	1
membrane	1
cell periphery	1
dendrite	1
neuron spine	1
postsynapse	1
cell junction	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTCHD1	SHANK2	Q9UPX8	845
PTCHD1	DLGAP2	Q9P1A6	842
PTCHD1	NLGN4X	Q8N0W4	804
PTCHD1	NLGN3	Q9NZ94	801
PTCHD1	SHH	Q15465	732
PTCHD1	DDX53	Q86TM3	729
PTCHD1	SYNGAP1	Q96PV0	726
PTCHD1	CNTNAP2	Q9UHC6	721
PTCHD1	SHANK3	Q9BYB0	711
PTCHD1	SLC9A9	Q8IVB4	668
PTCHD1	ASTN2	O75129	626
PTCHD1	AUTS2	Q8WXX7	601
PTCHD1	CDH9	Q9ULB4	593
PTCHD1	CNTN4	Q8IWV2	590
PTCHD1	MECP2	P51608	587

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PTCHD1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.440
PTCHD1	SNAPIN	psi-mi:“MI:0403”(colocalization)	0.440
PTCHD1	A2M	psi-mi:“MI:0915”(physical association)	0.370
ANKRD55	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
ATG5	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
CPLX2	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
PTCHD1	DCAF17	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
GFM2	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
HSPD1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
KDM1A	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
KLHL32	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
METAP2	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
NOL4	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
PDZD2	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
PON1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
PSMD14	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
STMN2	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
SYNE1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
TADA1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
TTC8	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
PTCHD1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.370
ZNF277	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
ZNF350	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
Cox11	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
Atoh1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
Pax3	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
ANKRD49	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
PTCHD1	DDX3X	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): PTCHD1 (Positive Genetic), PTCHD1 (Affinity Capture-RNA)

ESM2 similar proteins: A2AIR5, A5PK40, A6NFX1, B9EKX1, D2HKB0, D3ZG27, F1NCD6, O60242, P23979, P46098, P62955, P62956, P62957, Q08DW9, Q0VBU9, Q13635, Q14B62, Q3T9X0, Q4R766, Q504N2, Q5H8A4, Q5RB09, Q5RIV7, Q5T4D3, Q5VTY9, Q5VYX0, Q5VZY2, Q5ZIN0, Q61115, Q66H95, Q6AYT7, Q6ZW05, Q80ZF8, Q8BG19, Q8BWB6, Q8IZD6, Q8N2K0, Q8N6M3, Q8NEB5, Q8NHX9

Diamond homologs: B9EKX1, Q14B62, Q5RIV7, Q6ZW05, Q96NR3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PTCHD1	“up-regulates quantity”	DLG4	binding
PTCHD1	“up-regulates quantity”	VPS35	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	24
Uncertain significance	213
Likely benign	45
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1526772	GRCh37/hg19 Xp22.11(chrX:23198764-23542640)	Pathogenic
1695330	GRCh37/hg19 Xp22.11(chrX:23352993-23412302)x0	Pathogenic
208739	NM_173495.3(PTCHD1):c.1835_1839delinsGAA (p.Met612fs)	Pathogenic
2579657	GRCh37/hg19 Xp22.11(chrX:23209046-23383351)	Pathogenic
2685700	GRCh37/hg19 Xp22.11(chrX:23164537-23400286)x1	Pathogenic
3062548	GRCh37/hg19 Xp22.11(chrX:23280708-23387267)	Pathogenic
3254644	NM_173495.3(PTCHD1):c.1082_1083dup (p.Glu362fs)	Pathogenic
3391629	NM_173495.3(PTCHD1):c.145G>T (p.Glu49Ter)	Pathogenic
442877	GRCh37/hg19 Xp22.11(chrX:23351370-23449835)x0	Pathogenic
521561	NM_173495.3(PTCHD1):c.590_603del (p.Val197fs)	Pathogenic
685338	GRCh37/hg19 Xp22.11(chrX:23195843-23457401)x0	Pathogenic
818018	NM_173495.3(PTCHD1):c.590_591del (p.Val197fs)	Pathogenic
984750	GRCh37/hg19 Xp22.11(chrX:23395622-23463363)x0	Pathogenic
986799	NM_173495.3(PTCHD1):c.1794_1806del (p.Asn599fs)	Pathogenic
1064443	NM_173495.3(PTCHD1):c.95C>G (p.Pro32Arg)	Likely pathogenic
1251937	NM_173495.3(PTCHD1):c.1434C>G (p.Tyr478Ter)	Likely pathogenic
1707515	NM_173495.3(PTCHD1):c.1557T>G (p.Tyr519Ter)	Likely pathogenic
1767638	NM_173495.3(PTCHD1):c.963del (p.Gly322fs)	Likely pathogenic
2499957	NM_173495.3(PTCHD1):c.2582dup (p.Asn861fs)	Likely pathogenic
2501715	NM_173495.3(PTCHD1):c.1434C>A (p.Tyr478Ter)	Likely pathogenic
2506479	NM_173495.3(PTCHD1):c.2097_2098insA (p.Leu700fs)	Likely pathogenic
280396	NM_173495.3(PTCHD1):c.1547T>A (p.Leu516Ter)	Likely pathogenic
3372171	NM_173495.3(PTCHD1):c.2132TCT[2] (p.Phe713del)	Likely pathogenic
3376263	NM_173495.3(PTCHD1):c.1164dup (p.Gly389fs)	Likely pathogenic
372479	NM_173495.3(PTCHD1):c.1969_1972del (p.Asn657fs)	Likely pathogenic
4071991	NM_173495.3(PTCHD1):c.154_160del (p.Val52fs)	Likely pathogenic
423632	NM_173495.3(PTCHD1):c.1433dup (p.Tyr478Ter)	Likely pathogenic
424379	NM_173495.3(PTCHD1):c.2T>C (p.Met1Thr)	Likely pathogenic
436440	NM_173495.3(PTCHD1):c.893G>A (p.Trp298Ter)	Likely pathogenic
4628588	NM_173495.3(PTCHD1):c.2161dup (p.Ser721fs)	Likely pathogenic

SpliceAI

987 predictions. Top by Δscore:

Variant	Effect	Δscore
X:23379589:A:AG	acceptor_gain	1.0000
X:23379589:AGTT:A	acceptor_gain	1.0000
X:23379590:G:GA	acceptor_gain	1.0000
X:23379590:GTT:G	acceptor_gain	1.0000
X:23379590:GTTG:G	acceptor_gain	1.0000
X:23379590:GTTGC:G	acceptor_gain	1.0000
X:23335224:AAGG:A	donor_loss	0.9900
X:23335226:GGTG:G	donor_loss	0.9900
X:23335227:G:GA	donor_loss	0.9900
X:23335228:T:A	donor_loss	0.9900
X:23376897:T:G	donor_gain	0.9900
X:23379586:CACAG:C	acceptor_loss	0.9900
X:23379587:ACAGT:A	acceptor_loss	0.9900
X:23379588:C:G	acceptor_gain	0.9900
X:23379588:CAGT:C	acceptor_loss	0.9900
X:23379589:AG:A	acceptor_loss	0.9900
X:23379590:G:C	acceptor_loss	0.9900
X:23379590:GT:G	acceptor_gain	0.9900
X:23380230:G:GT	donor_gain	0.9800
X:23380247:GCTAG:G	donor_gain	0.9800
X:23380248:C:G	donor_gain	0.9800
X:23379587:A:AG	acceptor_gain	0.9700
X:23380248:CTAGG:C	donor_loss	0.9700
X:23380249:TAGGT:T	donor_loss	0.9700
X:23380250:AGGTA:A	donor_loss	0.9700
X:23380251:GGTA:G	donor_loss	0.9700
X:23380252:GTA:G	donor_loss	0.9700
X:23380253:T:A	donor_loss	0.9700
X:23391338:A:G	donor_gain	0.9700
X:23334964:C:A	acceptor_gain	0.9600

AlphaMissense

5857 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:23379658:G:A	C140Y	1.000
X:23379659:T:G	C140W	1.000
X:23379681:T:A	C148S	1.000
X:23379682:G:C	C148S	1.000
X:23393277:T:A	W587R	1.000
X:23393277:T:C	W587R	1.000
X:23393451:T:C	S645P	1.000
X:23335095:T:C	F74L	0.999
X:23335096:T:C	F74S	0.999
X:23335096:T:G	F74C	0.999
X:23335097:C:A	F74L	0.999
X:23335097:C:G	F74L	0.999
X:23335156:G:A	G94D	0.999
X:23335159:G:C	R95P	0.999
X:23379657:T:A	C140S	0.999
X:23379657:T:C	C140R	0.999
X:23379658:G:C	C140S	0.999
X:23379658:G:T	C140F	0.999
X:23379681:T:C	C148R	0.999
X:23379682:G:A	C148Y	0.999
X:23379683:C:G	C148W	0.999
X:23379766:C:A	P176Q	0.999
X:23379804:G:T	G189W	0.999
X:23379805:G:A	G189E	0.999
X:23379817:G:A	G193E	0.999
X:23379861:G:C	A208P	0.999
X:23379924:T:A	W229R	0.999
X:23379924:T:C	W229R	0.999
X:23379926:G:C	W229C	0.999
X:23379926:G:T	W229C	0.999

dbSNP variants (sampled 300 via entrez): RS1000028083 (X:23366370 A>G), RS1000084651 (X:23357459 A>G), RS1000186700 (X:23360514 A>T), RS1000216269 (X:23360155 G>T), RS1000239524 (X:23367444 A>C), RS1000291792 (X:23366991 C>T), RS1000306551 (X:23404416 G>A), RS1000338870 (X:23404620 A>G), RS1000377342 (X:23353759 G>A), RS1000439409 (X:23376449 A>G), RS1000519212 (X:23361812 G>T), RS1000550256 (X:23361612 G>A), RS1000589265 (X:23336836 T>C), RS1000640910 (X:23357766 C>T), RS1000731917 (X:23348452 A>G)

Disease associations

OMIM: gene MIM:300828 | disease phenotypes: MIM:300830, MIM:615879, MIM:309530

GenCC curated gene-disease

Disease	Classification	Inheritance
autism, susceptibility to, X-linked 4	Definitive	X-linked
non-syndromic X-linked intellectual disability	Strong	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Definitive	XL

Mondo (6): intellectual disability (MONDO:0001071), autism, susceptibility to, X-linked 4 (MONDO:0010440), neurodevelopmental disorder (MONDO:0700092), Tatton-Brown-Rahman overgrowth syndrome (MONDO:0014382), non-syndromic X-linked intellectual disability (MONDO:0019181), autism spectrum disorder (MONDO:0005258)

Orphanet (5): Tatton-Brown-Rahman syndrome (Orphanet:404443), X-linked non-syndromic intellectual disability (Orphanet:777), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001419	X-linked recessive inheritance
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder
HP:0100034	Motor tics
HP:0100710	Impulsivity

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001538_26	Immune reponse to smallpox (secreted IFN-alpha)	1.000000e-07
GCST002868_19	Response to serotonin reuptake inhibitors in major depressive disorder	6.000000e-06
GCST003479_11	Hair color	5.000000e-07
GCST007665_7	Treatment resistant depression	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0009854	treatment resistant depression

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7051085	PTCHD1		0.00	0

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	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	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Atrazine	increases expression	1
Lead	affects expression	1
Silicon Dioxide	increases expression	1
Tunicamycin	increases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
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
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study