PCDHGB1

protein-coding

protocadherin gamma subfamily B, 1, the group of Clustered protocadherins

Gene summary

This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

MANE transcript

NM_018922.3

Inheritance

—

ClinVar variants

U:132B:15

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr5:141,350,099-141,512,975

External References & Databases

Ensembl (ENSG00000254221)

Transcript & Mutation Effects

hg38 • Region Span ~162.9 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 PCDHGB1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 2271

Inborn genetic diseasesTotal: 104

not providedTotal: 69

Neurodevelopmental disorder with poor growth and skeletal anomaliesTotal: 11

PCDHGC4-related disorderTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 3

Neurodevelopmental disorderTotal: 1

Complex neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018922.3. 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			132 clinvar	9 clinvar		141
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	132	14	1	147

Highest pathogenic variant AF is 0.0000043382875

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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_018922.3	RefSeq	NP_061745.1	4	MANE Select
ENST00000523390.2	Ensembl	ENSP00000429273.1	4	MANE Select
NM_032095.1	RefSeq	NP_115266.1	1	Standard
ENST00000611598.1	Ensembl	ENSP00000478900.1	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

Molecular Function

calcium ion binding

Cellular Component

integral component of plasma membrane
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000523390
Coding exons: 4
Length: 162719
Individuals with no LoFs: 124466
Homozygous LoFs: 1
Heterozygous LoFs: 228
Defined: 124695
p: 0.000919

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.104	561	568	0.988	0.0000360	6022
Missense (PolyPhen)		208	209.07	0.99489		2319
Synonymous	-2.02	294	253	1.16	0.0000184	1970
Loss of Function	2.63	11	25.3	0.435	0.00000136	294

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00028	0.00026	rare
Latino/Admixed American	0.0018	0.0018	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0042	0.0042	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00062	0.00061	rare
South Asian	0.00042	0.00042	rare
Other	0.00083	0.00083	rare

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: 0.400
RVIS EVS: -0.86
RVIS percentile EVS: 10.92

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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