PCDHB4

protein-coding

protocadherin beta 4, the group of Clustered protocadherins

Gene summary

This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]

MANE transcript

NM_018938.4

Inheritance

—

ClinVar variants

U:134B:24

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr5:141,121,818-141,125,623

External References & Databases

Ensembl (ENSG00000081818)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 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 PCDHB4 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 20

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

EpilepsyTotal: 1

SeizureTotal: 1

Intellectual disabilityTotal: 1

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018938.4. 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				9 clinvar	2 clinvar	11
missense			133 clinvar	5 clinvar	7 clinvar	145
nonsense						0
start loss						0
frameshift			1 clinvar		1 clinvar	2
splice donor/acceptor (+/-2bp)						0
Total	0	0	134	14	10	158

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018938.4	RefSeq	NP_061761.1	1	MANE Select
ENST00000194152.4	Ensembl	ENSP00000194152.1	1	MANE Select

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
chemical synaptic transmission
nervous system development
synapse assembly

Molecular Function

calcium ion binding

Cellular Component

integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000194152
Coding exons: 1
Length: 3621
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.341	479	458	1.04	0.0000293	5107
Missense (PolyPhen)		129	138.23	0.93321		1648
Synonymous	-2.77	266	214	1.24	0.0000161	1728
Loss of Function	0.298	18	19.4	0.927	0.00000128	214

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	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.;

Intolerance Scores

LoFtool: 0.933
RVIS EVS: 0.8
RVIS percentile EVS: 87.72

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.145

Gene Damage Prediction

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