TPCN2

two pore segment channel 2, the group of Two pore segment channels|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:69048932-69136316

Links

ENSG00000162341 ∙ NCBI:219931 ∙ OMIM:612163 ∙ HGNC:20820 ∙ Uniprot:Q8NHX9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Skin/hair/eye pigmentation, variation in, 10	AD	General	The condition may not be clinically relevant	Dermatologic	18488028
Variants may be involved in sun sensitivity

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPCN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPCN2 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	4	5
missense			52	4	4	60
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding						0
Total	0	0	52	5	8

Variants in TPCN2

This is a list of pathogenic ClinVar variants found in the TPCN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-69049013-G-A		not specified	Uncertain significance (Oct 02, 2023)
11-69049014-C-T		not specified	Uncertain significance (Mar 11, 2024)
11-69049024-G-T		not specified	Uncertain significance (Aug 23, 2021)
11-69049065-C-T		not specified	Uncertain significance (Nov 22, 2021)
11-69054038-G-T		not specified	Uncertain significance (Dec 02, 2022)
11-69054082-C-T			Likely benign (Jul 01, 2022)
11-69054740-G-A		not specified	Uncertain significance (Sep 29, 2023)
11-69054755-C-T		not specified	Uncertain significance (Sep 01, 2021)
11-69054787-G-A			Benign (May 18, 2018)
11-69054796-C-T			Benign (May 14, 2018)
11-69055190-C-T			Benign (Dec 31, 2019)
11-69055234-C-T		not specified	Uncertain significance (Jun 26, 2023)
11-69055236-C-G		not specified	Uncertain significance (Apr 06, 2022)
11-69055249-C-T		not specified	Uncertain significance (Nov 08, 2021)
11-69055275-T-C		not specified	Uncertain significance (May 06, 2024)
11-69055302-A-T		not specified	Uncertain significance (Sep 26, 2023)
11-69057590-G-A		not specified	Uncertain significance (Apr 13, 2022)
11-69057627-G-A		not specified	Uncertain significance (May 27, 2022)
11-69057683-G-A		not specified	Uncertain significance (Feb 10, 2023)
11-69057698-G-C			Likely benign (Aug 15, 2018)
11-69062909-G-A		not specified	Uncertain significance (Apr 14, 2022)
11-69062917-T-C		Skin/hair/eye pigmentation, variation in, 10	Uncertain significance (-)
11-69062933-C-T		not specified	Uncertain significance (Nov 27, 2023)
11-69062972-C-T		not specified	Uncertain significance (May 03, 2023)
11-69062986-G-T		not specified	Uncertain significance (Jul 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPCN2	protein_coding	protein_coding	ENST00000294309	25	41708

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.12e-10	1.00	125659	0	89	125748	0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.451	412	439	0.939	0.0000278	4827
Missense in Polyphen		151	180.17	0.83812		1886
Synonymous	0.349	185	191	0.968	0.0000126	1528
Loss of Function	3.30	24	48.9	0.491	0.00000265	492

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00105	0.00105
Ashkenazi Jewish	0.000108	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000379	0.000360
Middle Eastern	0.000381	0.000381
South Asian	0.000262	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal membrane. May be involved in smooth muscle contraction. {ECO:0000269|PubMed:19387438, ECO:0000269|PubMed:19620632}.
• Pathway: Pancreatic secretion - Homo sapiens (human);VEGFA-VEGFR2 Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.0941
• rvis_EVS: -0.34
• rvis_percentile_EVS: 29.62

Haploinsufficiency Scores

• pHI: 0.0740
• hipred: N
• hipred_score: 0.332
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.170

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tpcn2
• Phenotype: endocrine/exocrine gland phenotype; hematopoietic system phenotype; normal phenotype; skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: tpcn2
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cellular calcium ion homeostasis;smooth muscle contraction;lysosome organization;regulation of autophagy;calcium-mediated signaling;response to vitamin D;ion transmembrane transport;regulation of ion transmembrane transport;release of sequestered calcium ion into cytosol
• Cellular component: lysosome;lysosomal membrane;endosome membrane;integral component of membrane
• Molecular function: voltage-gated calcium channel activity;protein binding;protein kinase binding;identical protein binding;NAADP-sensitive calcium-release channel activity