PTCHD1

protein-coding

patched domain containing 1

Gene summary

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). [provided by RefSeq, Aug 2011]

MANE transcript

NM_173495.3

Inheritance

ClinVar variants

P:37U:261B:67

Top phenotype

Autism susceptibility, X-linked 4

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chrX:23,334,849-23,404,374

External References & Databases

Ensembl (ENSG00000165186)

Transcript & Mutation Effects

hg38 • Region Span ~69.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism, susceptibility to, X-linked 4DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010440

Submitter: G2P

autism, susceptibility to, X-linked 4DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010440

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

autism, susceptibility to, X-linked 4STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010440

Submitter: Labcorp Genetics (formerly Invitae)

X-linked complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0100148

Submitter: ClinGen

*PTCHD1* encodes a transmembrane protein that plays a crucial role in regulating synaptic function. *PTCHD1* was first reported in relation to X-linked complex neurodevelopmental disorder in 2015 (Chaudhry et al., PMID: 25131214). The clinical features of affected males include developmental delay, variable degrees of intellectual disability, and autism spectrum disorder or autistic features. Additionally, some patients may present hypotonia and subtle dysmorphic features. Females are usually unaffected. Nine variants (frameshift and single gene deletions) that have been reported in nine probands in four publications (PMIDs: 25131214, 25356970, 26350204, 28934986) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by a mouse model (PMID: 27007844). In summary, there is definitive evidence supporting the relationship between *PTCHD1* and X-linked complex neurodevelopmental disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on August 15, 2018 (SOP Version 5). As of November 2025, this record underwent administrative updates to include an evidence summary text and update scoring to be consistent with SOP Version 11. No new evidence was added.

non-syndromic X-linked intellectual disabilitySTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0019181

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Autism susceptibility, X-linked 4XL

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 18252227; 21091464; 25131214

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTCHD1 variants in ClinVar

17 Conditions Cataloged

not providedTotal: 188

Inborn genetic diseasesTotal: 112

Autism, susceptibility to, X-linked 4Total: 38

not specifiedTotal: 31

PTCHD1-related disorderTotal: 24

Non-syndromic X-linked intellectual disabilityTotal: 4

Intellectual disabilityTotal: 2

Tatton-Brown-Rahman overgrowth syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173495.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			19 clinvar	42 clinvar	1 clinvar	62
missense		5 clinvar	232 clinvar	22 clinvar	2 clinvar	261
nonsense	1 clinvar	10 clinvar	2 clinvar			13
start loss		1 clinvar				1
frameshift	5 clinvar	15 clinvar	7 clinvar			27
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	6	31	261	64	3	365

Highest pathogenic variant AF is 9.257708e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173495.3	RefSeq	NP_775766.2	3	MANE Select
ENST00000379361.5	Ensembl	ENSP00000368666.4	3	MANE Select
ENST00000456522.1	Ensembl	ENSP00000406663.1	2	Standard
ENST00000903588.1	Ensembl	ENSP00000573647.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

smoothened signaling pathway
thalamus development
social behavior
cognition

Molecular Function

molecular_function

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379361
Coding exons: 3
Length: 70357
Individuals with no LoFs: 125350
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125351
p: 0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.00	238	342	0.695	0.0000258	5849
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000052	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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 (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.238

Gene Damage Prediction

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