PCDH11X

protein-coding

protocadherin 11 X-linked, the group of Non-clustered protocadherins|Protein phosphatase 1 regulatory subunits

Gene summary

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Previous symbols:

PCDH11

MANE transcript

NM_032968.5

Inheritance

—

ClinVar variants

U:162B:23

Top phenotype

PCDH11X-related disorder

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chrX:91,779,261-92,623,230

External References & Databases

Ensembl (ENSG00000102290)

Transcript & Mutation Effects

hg38 • Region Span ~844.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PCDH11X variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 28

PCDH11X-related disorderTotal: 1

Alzheimer diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032968.5. 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			10 clinvar	7 clinvar	5 clinvar	22
missense			149 clinvar	8 clinvar	3 clinvar	160
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	162	15	8	185

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032968.5	RefSeq	NP_116750.1	7	MANE Select
ENST00000682573.1	Ensembl	ENSP00000507225.1	7	MANE Select
NM_001168360.1	RefSeq	NP_001161832.1	6	Standard
NM_001168361.1	RefSeq	NP_001161833.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell adhesion
homophilic cell adhesion via plasma membrane adhesion molecules
negative regulation of phosphatase activity

Molecular Function

calcium ion binding

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373094
Coding exons: 7
Length: 843970
Individuals with no LoFs: 125730
Homozygous LoFs: 8
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.30	356	501	0.711	0.0000379	8878
Missense (PolyPhen)		88	195.52	0.45007		3799
Synonymous	-0.878	210	194	1.08	0.0000155	2750
Loss of Function	3.25	8	25.8	0.310	0.00000207	471

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00015	0.00012	rare
Latino/Admixed American	0.000036	0.000029	rare
Ashkenazi Jewish	0.00027	0.00020	rare
East Asian	0.00022	0.00016	rare
Finnish	0.000062	0.000046	rare
European (Non-Finnish)	0.000050	0.000035	rare
South Asian	0.00010	0.000065	rare
Other	0.00044	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential calcium-dependent cell-adhesion protein.;

Recessive Scores

pRec: 0.0851

Intolerance Scores

LoFtool: 0.455
RVIS EVS: -0.22
RVIS percentile EVS: 37.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.101

Gene Damage Prediction

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