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

albinism (Limited), mode of inheritance: AD

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.

not_specified (120 variants)
not_provided (10 variants)
TPCN2-related_condition (3 variants)
SKIN/HAIR/EYE_PIGMENTATION,_VARIATION_IN,_10 (2 variants)
Marfanoid_habitus_and_intellectual_disability (1 variants)

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. These statistics are base on transcript: NM_000139075.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	2 clinvar	4 clinvar	10
missense		1 clinvar	123 clinvar	5 clinvar	3 clinvar	132
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	1	136	7	7

Highest pathogenic variant AF is 0.0000024784345

Loading clinvar variants...

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