PTCHD1

patched domain containing 1

Basic information

Region (hg38): X:23334849-23404374

Links

ENSG00000165186 ∙ NCBI:139411 ∙ OMIM:300828 ∙ HGNC:26392 ∙ Uniprot:Q96NR3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic X-linked intellectual disability (Definitive), mode of inheritance: XL
• autism, susceptibility to, X-linked 4 (Strong), mode of inheritance: XL
• autism, susceptibility to, X-linked 4 (Definitive), mode of inheritance: XL
• autism, susceptibility to, X-linked 4 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autism susceptibility, X-linked 4	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	18252227; 21091464; 25131214

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTCHD1 gene.

• not_provided (169 variants)
• Inborn_genetic_diseases (104 variants)
• Autism,_susceptibility_to,_X-linked_4 (36 variants)
• not_specified (23 variants)
• PTCHD1-related_disorder (13 variants)
• Intellectual_disability (2 variants)
• Non-syndromic_X-linked_intellectual_disability (2 variants)
• Tatton-Brown-Rahman_overgrowth_syndrome (1 variants)
• Neurodevelopmental_disorder (1 variants)
• PTCHD1-related_neurodevelopmental_disorder (1 variants)
• PTCHD1-related_autism_and_intellectual_disability (1 variants)
• Autism_spectrum_disorder (1 variants)
• Abnormal_brain_morphology (1 variants)
• See_cases (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTCHD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000173495.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			19	34	1	54
missense	1	5	204	23	2	235
nonsense	1	8	2			11
start loss		1				1
frameshift	5	12	7			24
splice donor/acceptor (+/-2bp)			1			1
Total	7	26	233	57	3

Highest pathogenic variant AF is 9.257708e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTCHD1	protein_coding	protein_coding	ENST00000379361	3	70357

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125350	0	1	125351	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.00	238	342	0.695	0.0000258	5849
Missense in Polyphen		69	135.04	0.51096		2434
Synonymous	-0.225	148	145	1.02	0.0000114	1794
Loss of Function	3.56	1	16.7	0.0599	0.00000112	336

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000524	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000250|UniProtKB:Q14B62}.

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.0945
• rvis_EVS: -1
• rvis_percentile_EVS: 8.32

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.238

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: smoothened signaling pathway;thalamus development;social behavior;cognition
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: molecular_function