PCDHGC4

protocadherin gamma subfamily C, 4, the group of Clustered protocadherins

Basic information

Region (hg38): 5:141484997-141512975

Links

ENSG00000242419 ∙ NCBI:56098 ∙ OMIM:606305 ∙ HGNC:8717 ∙ Uniprot:Q9Y5F7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with poor growth and skeletal anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with poor growth and skeletal anomalies	AR	General	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	Craniofacial; Musculoskeletal; Neurologic	34244665

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCDHGC4 gene.

• Neurodevelopmental disorder with poor growth and skeletal anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCDHGC4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense		1	58	2		61
nonsense		1				1
start loss						0
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			52	3	5	60
Total	1	4	110	8	6

Variants in PCDHGC4

This is a list of pathogenic ClinVar variants found in the PCDHGC4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-141485217-C-T			Likely benign (Apr 01, 2025)
5-141485229-T-A		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
5-141485242-C-A		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
5-141485247-G-C		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
5-141485291-C-A		Inborn genetic diseases	Uncertain significance (Dec 23, 2021)
5-141485291-C-T		Neurodevelopmental disorder with poor growth and skeletal anomalies	Pathogenic (May 20, 2022)
5-141485336-G-A		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
5-141485354-G-C		Inborn genetic diseases	Uncertain significance (Nov 23, 2024)
5-141485364-T-C		Inborn genetic diseases	Uncertain significance (Mar 24, 2023)
5-141485366-CAG-C		Neurodevelopmental disorder with poor growth and skeletal anomalies	Likely pathogenic (-)
5-141485441-A-C		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
5-141485491-G-A			Likely benign (Jan 01, 2025)
5-141485494-GT-G		Neurodevelopmental disorder with poor growth and skeletal anomalies	Pathogenic (May 20, 2022)
5-141485507-G-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
5-141485539-G-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
5-141485562-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2021)
5-141485585-C-G		Inborn genetic diseases	Uncertain significance (Apr 28, 2023)
5-141485635-G-A			Uncertain significance (-)
5-141485721-AG-A		Neurodevelopmental disorder with poor growth and skeletal anomalies	Pathogenic (Jun 05, 2024)
5-141485739-G-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2024)
5-141485768-C-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2025)
5-141485784-A-G		Inborn genetic diseases	Uncertain significance (Jan 22, 2025)
5-141485792-G-T		Inborn genetic diseases	Uncertain significance (May 18, 2022)
5-141485816-G-T		Inborn genetic diseases	Uncertain significance (Oct 09, 2024)
5-141485822-G-A		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCDHGC4	protein_coding	protein_coding	ENST00000306593	4	27806

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.980	0.0197	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.97	422	552	0.764	0.0000320	6053
Missense in Polyphen		76	148.13	0.51306		1768
Synonymous	2.15	187	228	0.819	0.0000132	2080
Loss of Function	4.36	4	29.6	0.135	0.00000193	293

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

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.

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.176
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.82

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.440
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcdhgc4

Gene ontology

• Biological process: cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;synapse organization
• Cellular component: integral component of plasma membrane
• Molecular function: calcium ion binding