PCDHA7

protein-coding

protocadherin alpha 7, the group of Clustered protocadherins

Gene summary

This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

Previous symbols:

CNRS4

MANE transcript

NM_018910.3

Inheritance

—

ClinVar variants

U:139B:16

Top phenotype

PCDHA9-related disorder

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr5:140,834,248-141,012,347

External References & Databases

Ensembl (ENSG00000204963)

Transcript & Mutation Effects

hg38 • Region Span ~178.1 kb

Loading mutation effect viewer...

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 PCDHA7 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 1374

not providedTotal: 68

PCDHA9-related disorderTotal: 35

EBV-positive nodal T- and NK-cell lymphomaTotal: 2

PCDHA13-related disorderTotal: 2

Prostate cancerTotal: 1

PCDHA12-related conditionTotal: 1

ThrombocytosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018910.3. 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				5 clinvar	1 clinvar	6
missense			139 clinvar	10 clinvar		149
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	139	15	1	155

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018910.3	RefSeq	NP_061733.1	4	MANE Select
ENST00000525929.2	Ensembl	ENSP00000436426.1	4	MANE Select
NM_031852.2	RefSeq	NP_114040.1	1	Standard
ENST00000356878.5	Ensembl	ENSP00000349344.5	1	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
nervous system development
cell-cell recognition

Molecular Function

calcium ion binding
identical protein binding

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000525929
Coding exons: 4
Length: 177961
Individuals with no LoFs: 125562
Homozygous LoFs: 1
Heterozygous LoFs: 185
Defined: 125748
p: 0.000740

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.18	641	562	1.14	0.0000403	5986
Missense (PolyPhen)		132	121.31	1.0881		1411
Synonymous	-2.81	330	271	1.22	0.0000238	2042
Loss of Function	1.62	17	25.9	0.657	0.00000143	304

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00058	0.00055	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.0042	0.0041	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00034	0.00034	rare
South Asian	0.0013	0.0013	notable
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination. Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain. {ECO:0000250|UniProtKB:Q91Y13}.;

Intolerance Scores

LoFtool: 0.861
RVIS EVS: 0.08
RVIS percentile EVS: 59.18

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.111

Gene Damage Prediction

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