PDCD6

programmed cell death 6, the group of EF-hand domain containing

Basic information

Region (hg38): 5:271621-314974

Links

ENSG00000249915

∙ NCBI:10016 ∙ OMIM:601057 ∙ HGNC:8765 ∙ Uniprot:O75340 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDCD6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDCD6 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				1 clinvar		1
missense			14 clinvar			14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	1	0

Variants in PDCD6

This is a list of pathogenic ClinVar variants found in the PDCD6 region.

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

Position	Phenotype	Significance	ClinVar
5-271788-C-T	not specified	Uncertain significance (Sep 16, 2021)	2250323
5-272714-C-T		Likely benign (Feb 01, 2023)	2655242
5-272758-A-G	not specified	Uncertain significance (Dec 12, 2023)	2389323
5-272763-C-G	not specified	Uncertain significance (Jun 07, 2023)	2559104
5-272763-C-T	not specified	Uncertain significance (Jan 19, 2022)	2272431
5-272771-C-G	not specified	Uncertain significance (Dec 21, 2022)	3210584
5-304180-C-A	not specified	Uncertain significance (Jan 12, 2024)	3210585
5-306691-C-T	not specified	Uncertain significance (Jun 09, 2022)	2225202
5-306694-A-G	not specified	Uncertain significance (Feb 07, 2023)	2481898
5-306695-C-T	not specified	Uncertain significance (Jun 24, 2022)	2408440
5-306723-C-G	not specified	Uncertain significance (Apr 25, 2023)	2570142
5-311298-C-T	not specified	Uncertain significance (Sep 30, 2021)	2252883
5-311332-G-A	not specified	Uncertain significance (Dec 19, 2022)	2381565
5-311341-A-G	not specified	Uncertain significance (Nov 15, 2021)	2261683
5-314429-A-G	not specified	Uncertain significance (Oct 27, 2022)	2321109

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDCD6	protein_coding	protein_coding	ENST00000264933	6	82236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00888	0.942	125715	1	30	125746	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.454	111	125	0.886	0.00000871	1256
Missense in Polyphen		37	46.933	0.78836		494
Synonymous	0.146	53	54.4	0.975	0.00000462	350
Loss of Function	1.70	5	11.1	0.449	5.43e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000105
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Calcium sensor that plays a key role in processes such as endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal biogenesis or membrane repair. Acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium: calcium-binding triggers exposure of apolar surface, promoting interaction with different sets of proteins thanks to 3 different hydrophobic pockets, leading to translocation to membranes (PubMed:20691033, PubMed:25667979). Involved in ER-Golgi transport by promoting the association between PDCD6IP and TSG101, thereby bridging together the ESCRT- III and ESCRT-I complexes (PubMed:19520058). Together with PEF1, acts as calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in ER-Golgi transport by regulating the size of COPII coats (PubMed:27716508). In response to cytosolic calcium increase, the heterodimer formed with PEF1 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification (PubMed:27716508). Involved in the regulation of the distribution and function of MCOLN1 in the endosomal pathway (PubMed:19864416). Promotes localization and polymerization of TFG at endoplasmic reticulum exit site (PubMed:27813252). Required for T-cell receptor-, Fas-, and glucocorticoid-induced apoptosis (By similarity). May mediate Ca(2+)-regulated signals along the death pathway: interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (PubMed:16132846). Its role in apoptosis may however be indirect, as suggested by knockout experiments (By similarity). May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphorylation of the Akt signaling pathway (PubMed:21893193). In case of infection by HIV-1 virus, indirectly inhibits HIV-1 production by affecting viral Gag expression and distribution (PubMed:27784779). {ECO:0000250|UniProtKB:P12815, ECO:0000269|PubMed:16132846, ECO:0000269|PubMed:19520058, ECO:0000269|PubMed:19864416, ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25667979, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27784779, ECO:0000269|PubMed:27813252}.;

Recessive Scores

pRec: 0.164

Intolerance Scores

loftool: 0.280
rvis_EVS: -0.36
rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

pHI
hipred: Y
hipred_score: 0.806
ghis: 0.601

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.837

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pdcd6
Phenotype: normal phenotype;

Gene ontology

Biological process: angiogenesis;positive regulation of endothelial cell proliferation;intracellular protein transport;endoplasmic reticulum to Golgi vesicle-mediated transport;activation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of endothelial cell migration;neural crest formation;neural crest cell development;negative regulation of vascular endothelial growth factor receptor signaling pathway;negative regulation of TOR signaling;cellular response to heat;vascular endothelial growth factor receptor-2 signaling pathway;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of angiogenesis;COPII vesicle coating;response to calcium ion;negative regulation of protein kinase B signaling;apoptotic signaling pathway;positive regulation of protein monoubiquitination
Cellular component: Golgi membrane;nucleus;cytoplasm;endosome;endoplasmic reticulum;endoplasmic reticulum membrane;COPII vesicle coat;cytoplasmic vesicle;Cul3-RING ubiquitin ligase complex;extracellular exosome;endoplasmic reticulum exit site
Molecular function: magnesium ion binding;calcium ion binding;protein binding;identical protein binding;protein homodimerization activity;protein membrane anchor;protein dimerization activity;calcium-dependent protein binding;molecular adaptor activity