TPCN1

protein-coding

two pore segment channel 1, the group of MicroRNA protein coding host genes|Two pore segment channels

Gene summary

Voltage-gated Ca(2+) and Na+ channels have 4 homologous domains, each containing 6 transmembrane segments, S1 to S6. TPCN1 is similar to these channels, but it has only 2 domains containing S1 to S6 (Ishibashi et al., 2000 [PubMed 10753632]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_017901.6

Inheritance

—

ClinVar variants

U:95B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr12:113,221,050-113,298,585

External References & Databases

Ensembl (ENSG00000186815)

Transcript & Mutation Effects

hg38 • Region Span ~77.5 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 TPCN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017901.6. 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				1 clinvar	2 clinvar	3
missense			90 clinvar	3 clinvar	1 clinvar	94
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	95	4	3	102

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 96 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017901.6	RefSeq	NP_060371.2	27	MANE Select
ENST00000335509.11	Ensembl	ENSP00000335300.6	27	MANE Select
NM_001143819.3	RefSeq	NP_001137291.1	28	Standard
NM_001301214.2	RefSeq	NP_001288143.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Stimuli-sensing channels
Ion channel transport
Fibroblast growth factor-1
Transport of small molecules

Biological Process

positive regulation of autophagy
ion transmembrane transport
regulation of ion transmembrane transport
release of sequestered calcium ion into cytosol

Molecular Function

voltage-gated calcium channel activity
protein binding
identical protein binding
NAADP-sensitive calcium-release channel activity

Cellular Component

lysosome
lysosomal membrane
endosome
endosome membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000550785
Coding exons: 28
Length: 77536
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125748
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.44	381	540	0.705	0.0000339	5808
Missense (PolyPhen)		132	231.77	0.56953		2466
Synonymous	-0.688	240	227	1.06	0.0000151	1728
Loss of Function	4.83	15	52.9	0.283	0.00000270	586

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000093	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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 and endosomal membrane. {ECO:0000269|PubMed:19620632}.;

Intolerance Scores

LoFtool: 0.0929
RVIS EVS: -1.08
RVIS percentile EVS: 7.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.833

Gene Damage Prediction

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